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Zewail M, Abbas H, Sayed NE, Abd-El-Azim H. Intradermal delivery of teriflunomide loaded emulsomes using hollow microneedles for effective minimally invasive psoriasis management. Eur J Pharm Biopharm 2025; 210:114692. [PMID: 40081673 DOI: 10.1016/j.ejpb.2025.114692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 01/10/2025] [Accepted: 03/10/2025] [Indexed: 03/16/2025]
Abstract
Conventional topical psoriasis treatments suffer from limited delivery to affected areas along with skin irritation due to high local drug concentration. Herein an attempt to improve the delivery of leflunomide's active metabolite (teriflunomide (TER)) by improving its solubility through nanoencapsulation in emulsomes (EMLs) besides ensuring effective intradermal delivery using hollow microneedles. Evaluation of colloidal characteristics of EMLs, encapsulation efficiency and drug release were performed. Additionally, the antipsoriatic activity in an imiquimod-induced psoriatic mouse model was evaluated by the measurement of inflammatory mediators' levels and histopathological assessment of anatomized skin. The particle size of the chosen EMLs formulation was 147.9 nm and the zeta potential value was -21.7. Entrapment efficiency was 97.23 % and EMLs provided sustained drug release for 48 h. No statistically significant differences in the in vivo levels of NF-KB, IL 8, MMP1, GSH, SOD and catalase between the animals treated by TER-EMLs and the negative control cohort were observed. Also, histopathological inspection of dissected skin samples reflected the superiority of TER-EMLs over TER suspension. Collectively, combining nanoencapsulation and hollow microneedles application improved TER properties and ensured effective TER delivery to the affected psoriatic areas.
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Affiliation(s)
- Mariam Zewail
- Department of Pharmaceutics, Damanhour University, Damanhour, Egypt.
| | - Haidy Abbas
- Department of Pharmaceutics, Damanhour University, Damanhour, Egypt
| | - Nesrine El Sayed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Heba Abd-El-Azim
- Department of Pharmaceutics, Damanhour University, Damanhour, Egypt; Postdoc Brigham and Women's Hospital, Harvard Medical School, Harvard University, United States
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2
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Tarek M, El-Gogary RI, Kamel AO. A new era of psoriasis treatment: Drug repurposing through the lens of nanotechnology and machine learning. Int J Pharm 2025; 673:125385. [PMID: 39999900 DOI: 10.1016/j.ijpharm.2025.125385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/09/2025] [Accepted: 02/21/2025] [Indexed: 02/27/2025]
Abstract
Psoriasis is a persistent inflammatory skin disorder characterized by hyper-proliferation and abnormal epidermal differentiation. Conventional treatments such as; topical therapies, phototherapy, systemic immune modulators, and biologics aim to relieve symptoms and improve patient quality of life. However, challenges like adverse effects, high costs, and individual response variability persist. Thus, the need for novel anti-psoriatic drugs has led to the exploration of drug repurposing, an approach that identifies new applications for existing drugs. This method is in its early stages but has gained popularity across both public and private sectors. Furthermore, artificial intelligence (AI) integration is revolutionizing the healthcare industry by enhancing efficiency, delivery, and personalization. Machine learning and deep learning algorithms have significantly impacted drug discovery, repurposing, and designing new molecules or drug delivery carriers. Nanotechnology, in addition to AI, plays a pivotal role in targeting repurposed drugs via the topical route with suitable nanocarriers. This method overcomes challenges associated with oral delivery, such as systemic toxicities, slow onset of action, first-pass effect, and poor bioavailability. This review addresses the practice of repurposing existing drugs for managing psoriasis, discussing the challenges of conventional therapy and how the incorporation of nanotechnology and AI can overcome these hurdles, facilitating the discovery of anti-psoriatic drugs and presenting promising strategies for novel therapeutics. Additionally, it discusses the general benefits of drug repurposing compared to de novo drug development and the potential drawbacks of drug repurposing.
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Affiliation(s)
- Mahmoud Tarek
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt; Department of Pharmaceutics, Faculty of Pharmacy, Sinai University, Alarish, North Sinai 45511, Egypt
| | - Riham I El-Gogary
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt
| | - Amany O Kamel
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
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3
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Schreiber A, Ludwig S. Host-targeted antivirals against SARS-CoV-2 in clinical development - Prospect or disappointment? Antiviral Res 2025; 235:106101. [PMID: 39923941 DOI: 10.1016/j.antiviral.2025.106101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 02/05/2025] [Accepted: 02/06/2025] [Indexed: 02/11/2025]
Abstract
The global response to the COVID-19 pandemic, caused by the novel SARS-CoV-2 virus, has seen an unprecedented increase in the development of antiviral therapies. Traditional antiviral strategies have primarily focused on direct-acting antivirals (DAAs), which specifically target viral components. In recent years, increasing attention was given to an alternative approach aiming to exploit host cellular pathways or immune responses to inhibit viral replication, which has led to development of so-called host-targeted antivirals (HTAs). The emergence of SARS-CoV-2 and COVID-19 has promoted a boost in this field. Numerous HTAs have been tested and demonstrated their potential against SARS-CoV-2 through in vitro and in vivo studies. However, in striking contrast, only a limited number have successfully progressed to advanced clinical trial phases (2-4), and even less have entered clinical practice. This review aims to explore the current landscape of HTAs targeting SARS-CoV-2 that have reached phase 2-4 clinical trials. Additionally, it will explore the challenges faced in the development of HTAs and in gaining regulatory approval and market availability.
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Affiliation(s)
- André Schreiber
- Institute of Virology Muenster, University of Muenster, Muenster, Germany
| | - Stephan Ludwig
- Institute of Virology Muenster, University of Muenster, Muenster, Germany.
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4
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Nash P, Sumpton D, Tellus M, Feletar M, Bird P, Hall S. A review and recommendations on the management of psoriatic arthritis in Australia 2024. Intern Med J 2024. [PMID: 39587898 DOI: 10.1111/imj.16557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 09/29/2024] [Indexed: 11/27/2024]
Abstract
Psoriatic arthritis (PsA) is a progressive, systemic inflammatory disease. It can lead to serious joint damage and disability, increased cardiovascular risk and reduced quality of life. Six experts met to develop the recommendations for the management of PsA in Australia. The final recommendations are approved by all panel members. Management and treatment recommendations have been made under six subheadings: Recommendations for non-steroidal anti-inflammatory drugs and glucocorticoids; Disease-modifying treatment; Screening and monitoring; Family planning; Symptom treatment and extra-articular manifestations; Comorbidities and lifestyle considerations. Our recommendations for the management of PsA in Australia draw heavily on the established global guidelines. These recommendations aim to assist clinicians to make informed, patient-centric choices when delivering treatment to people with PsA.
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Affiliation(s)
- Peter Nash
- School of Medicine, Griffith University, Brisbane, Queensland, Australia
- Rheumatology Research Unit, Sunshine Coast, Queensland, Australia
- Department of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Daniel Sumpton
- Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Michelle Tellus
- St Vincent's Private Hospital, Melbourne, Victoria, Australia
| | | | - Paul Bird
- School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Stephen Hall
- Melbourne Rheumatology, Cabrini Hospital, Melbourne, Victoria, Australia
- Monash University, Monash, Victoria, Australia
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5
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Yi RC, Gantz HY, Shah SC, Moran SK, Klionsky YE, Feldman SR. Pharmacotherapeutic management of psoriatic disease: addressing psoriatic arthritis and cutaneous manifestations. Expert Opin Pharmacother 2024; 25:2203-2212. [PMID: 39422251 DOI: 10.1080/14656566.2024.2419563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/27/2024] [Accepted: 10/17/2024] [Indexed: 10/19/2024]
Abstract
INTRODUCTION Psoriasis and psoriatic arthritis (PsA) are interrelated autoimmune conditions sharing similar genetic and immunological pathways. PsA often develops within 10 years of psoriasis onset, though it may precede cutaneous symptoms in some patients. Effective management of these conditions requires a multidisciplinary approach to address skin, bone, joint, and vascular manifestations. AREAS COVERED The review summarizes the current pharmacotherapies and to provide treatment guidelines for managing cutaneous psoriasis and PsA in psoriatic disease. EXPERT OPINION The management for mild psoriasis and mild PsA flare-ups can be addressed with topical treatments and with NSAIDs or intra-articular glucocorticoid injections. For more persistent or severe cases, systemic treatments with oral small molecules (Methotrexate, Apremilast, Janus kinase inhibitors) or with biologics (TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors, CTLA-4 Ig) are effective in managing both psoriasis and PsA. With many treatment options, providers can tailor management, which considers patient disease severity, preference, comorbidities, and other factors. Early detection and a multidisciplinary management strategy can optimize patient quality of life and improve health outcomes.
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Affiliation(s)
- Robin C Yi
- Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Hannah Y Gantz
- Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Shailey C Shah
- Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Shannon K Moran
- Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Yael E Klionsky
- Department of Internal Medicine, Section of Rheumatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Steven R Feldman
- Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
- Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
- Department of Social Sciences & Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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Jairath V, Acosta Felquer ML, Cho RJ. IL-23 inhibition for chronic inflammatory disease. Lancet 2024; 404:1679-1692. [PMID: 39461795 DOI: 10.1016/s0140-6736(24)01750-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 08/06/2024] [Accepted: 08/20/2024] [Indexed: 10/29/2024]
Abstract
Biological monoclonal antibody drugs inhibit overactive cytokine signalling that drives chronic inflammatory disease in different organ systems. In the last 10 years, interleukin (IL)-23 inhibitors have attained an important position in the treatment of psoriatic skin and joint disease as well as inflammatory bowel diseases. Addressing an upstream pathological mechanism shared between these disorders, this drug class has high efficacy rates and a durable response that extends dosing intervals up to 3 months. Pooled clinical trial data show objective disease improvement for more than 70% of patients with psoriasis and up to 50% of patients with inflammatory bowel disease. The first antibody inhibitor for IL-23A targeted a p40 subunit shared with IL-12. Subsequently, even greater improvement was established for inhibitors of the p19 protein unique to IL-23A. IL-23 p19 inhibitors elicit clinical response in both bio-naive and bio-exposed patients and show superiority to tumour necrosis factor α inhibitors in plaque psoriasis. Reported differences in efficacy between p19 inhibitors suggest that individual drug action might be modulated by antibody affinity. Although long-term safety data are accumulating, rates of serious adverse events and infections for interleukin (IL)-23 inhibitors are similar to the rates for placebo across approved indications.
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Affiliation(s)
- Vipul Jairath
- Departments of Medicine, Division of Gastroenterology, Western University, Ontario, ON, Canada
| | - Maria Laura Acosta Felquer
- Rheumatology Unit, Internal Medicine Service, Hospital Italiano de Buenos Aires and Instituto Universitario Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Raymond Jaihyun Cho
- Department of Dermatology, University of California, San Francisco, CA, USA.
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Proft F, Duran TI, Ghoreschi K, Pleyer U, Siegmund B, Poddubnyy D. Treatment strategies for Spondyloarthritis: Implementation of precision medicine - Or "one size fits all" concept? Autoimmun Rev 2024; 23:103638. [PMID: 39276959 DOI: 10.1016/j.autrev.2024.103638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/05/2024] [Accepted: 09/07/2024] [Indexed: 09/17/2024]
Abstract
Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations.
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Affiliation(s)
- Fabian Proft
- Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
| | - Tugba Izci Duran
- Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Clinic of Rheumatology, Denizli State Hospital, Denizli, Turkey
| | - Kamran Ghoreschi
- Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Uwe Pleyer
- Department of Ophthalmology Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin; Berlin, Germany and (5)Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Britta Siegmund
- Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Denis Poddubnyy
- Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Epidemiology unit, German Rheumatism Research Centre, Berlin, Germany; Division of Rheumatology, Department of Medicine, University Health Network and University of Toronto, Toronto, Canada
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8
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Ono K, Kishimoto M. Is JAK inhibitor the option to prevent difficult-to-manage axial spondyloarthritis? Int J Rheum Dis 2024; 27:e15329. [PMID: 39234892 DOI: 10.1111/1756-185x.15329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 07/30/2024] [Accepted: 08/28/2024] [Indexed: 09/06/2024]
Affiliation(s)
- Keisuke Ono
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Mitsumasa Kishimoto
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan
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Aboelwafa HO, Abou Khodair Mohamed H, Ibrahim DM, Bedair NI. Efficacy of Leflunomide Compared to Methotrexate in the Treatment of Moderate to Severe Plaques Psoriasis: A Randomized Controlled Clinical Trial. Dermatol Pract Concept 2024; 14:dpc.1403a165. [PMID: 39122533 PMCID: PMC11314144 DOI: 10.5826/dpc.1403a165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/25/2024] [Indexed: 08/12/2024] Open
Abstract
INTRODUCTION Psoriasis is a chronic inflammatory autoimmune skin disease. Several treatment options are available including topical and systemic options. Methotrexate was the main systemic medication in treating severe psoriasis, yet adverse events can limit its use. Leflunomide is an isoxazole derivative that inhibits the synthesis of pyrimidines, and subsequently inhibits RNA and DNA synthesis. OBJECTIVES As available data directly comparing MTX to leflunomide in psoriasis are lacking, this double blinded study was designed to compare the efficacy of methotrexate versus leflunomide in the treatment of moderate to severe psoriasis. METHODS The study included 40 patients (25 males and 15 females) with chronic plaque psoriasis. s. Patients were randomly assigned to one of two equal groups, group A for subcutaneous methotrexate injections and group B for leflunomide (loading dose 100mg daily for the first 3 days, then 20 mg daily for 3 months. Disease severity was determined by psoriasis area and severity index (PASI) score before and at the end of treatment The treatment response was evaluated at the baseline and weeks 4, 8 and 12 PASI score. RESULTS Both groups were matching at the baseline in aspects of gender, age, disease duration and PASI scores Both medications yielded comparable results with no significant difference between both groups in PASI score neither in side effects. CONCLUSIONS Leflunomide can be as effective as methotrexate in treatment of moderate to severe psoriasis.
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Affiliation(s)
- Hany Othman Aboelwafa
- Department of Dermatology, Venereology and Andrology, AlAzhar University- Damietta Faculty of Medicine, Damietta, Egypt
| | - Hassan Abou Khodair Mohamed
- Department of Dermatology, Venereology and Andrology, AlAzhar University- Damietta Faculty of Medicine, Damietta, Egypt
| | | | - Nermeen Ibrahim Bedair
- Department of Dermatology, Andrology, Sexual Medicine and STDs, Faculty of Medicine, Helwan University, Cairo, Egypt
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10
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Moon C, Porges E, Roberts A, Bacon J. A combination of nirmatrelvir and ombitasvir boosts inhibition of SARS-CoV-2 replication. Antiviral Res 2024; 225:105859. [PMID: 38492891 DOI: 10.1016/j.antiviral.2024.105859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 03/18/2024]
Abstract
Antiviral therapeutics are highly effective countermeasures for the treatment of coronavirus disease 2019 (COVID-19). However, development of resistance to antivirals undermines their effectiveness. Combining multiple antivirals during patient treatment has the potential to overcome the evolutionary selective pressure towards antiviral resistance, as well as provide a more robust and efficacious treatment option. The current evidence for effective antiviral combinations to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication is limited. Here, we demonstrate a combination of nirmatrelvir with ombitasvir, to jointly bring about potent inhibition of SARS-CoV-2 replication. We developed an in vitro 384- well plate cytopathic effect assay for the evaluation of antiviral combinations against Calu-3 cells infected with SARS-CoV-2 and found, that a combination of ombitasvir and nirmatrelvir was synergistic; thereby decreasing the nirmatrelvir IC50 by approx. 16-fold. The increased potency of the nirmatrelvir-ombitasvir combination, over nirmatrelvir alone afforded a greater than 3 log10 reduction in viral titre, which is sufficient to fully prevent the detection of progeny SARS-CoV-2 viral particles at 48 h post infection. The mechanism of this potentiated effect was shown to be, in-part, due to joint inhibition of the 3-chymotrypsin-like protease via a positive allosteric modulation mechanism.
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Affiliation(s)
- Christopher Moon
- Discovery Group, UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.
| | - Eleanor Porges
- Discovery Group, UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK
| | - Adam Roberts
- Discovery Group, UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK
| | - Joanna Bacon
- Discovery Group, UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK
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Bruggemeyer C, Nepal D, Putman M. Unintentional unblinding in rheumatic disease trials. THE LANCET. RHEUMATOLOGY 2023; 5:e633-e636. [PMID: 38251487 DOI: 10.1016/s2665-9913(23)00191-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/19/2023] [Accepted: 07/12/2023] [Indexed: 01/23/2024]
Abstract
The practice of blinding treatment assignment in randomised controlled trials mitigates important biases in observational studies. Unblinding, whereby study participants or investigators become aware of treatment assignments, is an important threat to the validity of trial results. Rheumatology studies might be particularly susceptible to unblinding because rheumatic disease therapies often cause high rates of idiosyncratic side-effects and frequently rely on subjective endpoints. Despite this susceptibility, the degree to which unblinding occurs in randomised controlled trials in rheumatic diseases has rarely been assessed during trials or acknowledged as a limitation. Rheumatologists should be aware of this important threat to the validity of trial results, assessments of unblinding should be undertaken, and strategies to prevent unblinding should be deployed when feasible.
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Affiliation(s)
- Cody Bruggemeyer
- Hub for Collaborative Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Desh Nepal
- Hub for Collaborative Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Michael Putman
- Hub for Collaborative Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
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12
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Ayan G, Ribeiro A, Macit B, Proft F. Pharmacologic Treatment Strategies in Psoriatic Arthritis. Clin Ther 2023; 45:826-840. [PMID: 37455227 DOI: 10.1016/j.clinthera.2023.05.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 07/18/2023]
Abstract
PURPOSE The goal of this narrative review was to provide current data on psoriatic arthritis (PsA) therapeutic strategies, supporting treatment decisions with a domain-based approach. METHODS This narrative review of treatment strategies for PsA focused on several disease domains (ie, peripheral arthritis, enthesitis, axial disease, dactylitis, skin and nail disease), as well as the so-called "related conditions" of uveitis, Crohn's disease, and ulcerative colitis. We searched PubMed, EMBASE, international guidelines, and recent congress abstracts. FINDINGS Currently, multiple approved treatment options offer a wide range of options, such as tumor necrosis factor (TNF) inhibitors; inhibitors of interleukin-17 (IL-17), IL-12/23 (IL-12/23), IL-23 (IL-23), and Janus kinase; the phosphodiesterase 4 inhibitor apremilast; and the T-cell modulator abatacept. However, no treatment option shows clear superiority concerning efficacy on peripheral arthritis and dactylitis over the others, whereas limited evidence suggests that the IL-17 inhibitor ixekizumab and the IL-12/23 inhibitor ustekinumab may be superior to TNF inhibitors in treating enthesitis. Recent data on enthesitis have also shown promising results for methotrexate. Treatment of axial PsA is mostly derived from axial spondyloarthritis, and more data are needed focusing on this specific subgroup of PsA patients. Thus far, the most important finding from the only randomized controlled trial in this specific population is that the IL-17 inhibitor secukinumab was superior to placebo in terms of clinical and radiologic end-points in axial PsA. Regarding psoriatic skin involvement, head-to-head trials in PsA as well as skin psoriasis showed the superiority of IL-17, IL-23, and IL-12/23 inhibitors over TNF inhibitors. When treating PsA with concurrent uveitis, according to the existing data, monoclonal TNF inhibitor antibodies should be preferred. In PsA and concomitant inflammatory bowel disease, treatment decisions must include the consideration of which specific type of inflammatory bowel disease (Crohn's disease or ulcerative colitis) is present, as some of the agents either lack data or are ineffective in treating these 2 conditions. In both types, IL-17 inhibitors should be avoided. When determining treatment strategy, comorbidities should be carefully assessed, and the corresponding risk profile of the respective treatment modalities should be taken into consideration. IMPLICATIONS There are many approved therapeutic options for treating patients with PsA, and additional emerging treatment options are in the pipeline. Individualized treatment decisions for each patient, depending on the leading disease phenotype, underlying comorbidities, and patient preferences, should be made based on shared decision-making.
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Affiliation(s)
- G Ayan
- Hacettepe University, Department of Internal Medicine, Division of Rheumatology, Ankara, Turkey
| | - A Ribeiro
- Hospital de Clínicas de Porto Alegre, Department of Rheumatology, Porto Alegre, Brazil
| | - Betul Macit
- Department of Dermatology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Fabian Proft
- Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité-Universitätsmedizin Berlin, Berlin, Germany.
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13
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Alhelal HM, Mehta S, Kadian V, Kakkar V, Tanwar H, Rao R, Aldhubiab B, Sreeharsha N, Shinu P, Nair AB. Solid Lipid Nanoparticles Embedded Hydrogels as a Promising Carrier for Retarding Irritation of Leflunomide. Gels 2023; 9:576. [PMID: 37504455 PMCID: PMC10379097 DOI: 10.3390/gels9070576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 07/02/2023] [Accepted: 07/11/2023] [Indexed: 07/29/2023] Open
Abstract
Leflunomide (LEF), a disease-modifying anti-rheumatic drug, has been widely explored for its anti-inflammatory potential in skin disorders such as psoriasis and melanoma. However, its poor stability and skin irritation pose challenges for topical delivery. To surmount these issues, LEF-loaded solid lipid nanoparticles (SLNs) integrated with hydrogels have been developed in the present investigation. SLNs developed by microemulsion techniques were found ellipsoidal with 273.1 nm particle size and -0.15 mV zeta potential. Entrapment and total drug content of LEF-SLNs were obtained as 65.25 ± 0.95% and 93.12 ± 1.72%, respectively. FTIR and XRD validated the successful fabrication of LEF-SLNs. The higher stability of LEF-SLNs (p < 0.001) compared to pure drug solution was observed in photostability studies. Additionally, in vitro anti-inflammatory activity of LEF-SLNs showed good potential in comparison to pure drugs. Further, prepared LEF-SLNs loaded hydrogel showed ideal rheology, texture, occlusion, and spreadability for topical drug delivery. In vitro release from LEF-SLN hydrogel was found to follow the Korsmeyer-Peppas model. To assess the skin safety of fabricated lipidic formulation, irritation potential was performed employing the HET-CAM technique. In conclusion, the findings of this investigation demonstrated that LEF-SLN hydrogel is capable of enhancing the photostability of the entrapped drug while reducing its skin irritation with improved topical delivery characteristics.
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Affiliation(s)
- Hawra Mohammed Alhelal
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Sidharth Mehta
- Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125001, India
| | - Varsha Kadian
- Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125001, India
| | - Vandita Kakkar
- Department of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Himanshi Tanwar
- Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125001, India
| | - Rekha Rao
- Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125001, India
| | - Bandar Aldhubiab
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Nagaraja Sreeharsha
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Department of Pharmaceutics, Vidya Siri College of Pharmacy, Off Sarjapura Road, Bangalore 560035, India
| | - Pottathil Shinu
- Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Anroop B Nair
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
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14
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Torosian K, Lal E, Kavanaugh A, Loomba R, Ajmera V, Guma M. Psoriatic disease and non-alcoholic fatty liver disease shared pathogenesis review. Semin Arthritis Rheum 2023; 59:152165. [PMID: 36716599 PMCID: PMC9992353 DOI: 10.1016/j.semarthrit.2023.152165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 12/03/2022] [Accepted: 01/04/2023] [Indexed: 01/20/2023]
Abstract
Psoriatic disease (PD) and non-alcoholic fatty liver disease (NAFLD) potentially share disease pathways given the numerous inflammatory pathways involved in both diseases and a higher prevalence of NAFLD in PD patients. Metabolic syndrome and obesity are a key link between the two diseases, but even when controlling for this, associations between both diseases are still seen. Therapeutics that impact metabolic or inflammatory pathways may be impactful in both PD and NAFLD. In this review, we describe common inflammatory pathways contributing to both PD and NAFLD and critically review the potential impact of treatments for and on both diseases.
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Affiliation(s)
- Kelly Torosian
- Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
| | - Esha Lal
- Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
| | - Arthur Kavanaugh
- Department of Rheumatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA
| | - Rohit Loomba
- Division of Gastroenterology and Hepatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA; NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, USA; Division of Epidemiology, Department of Family and Preventative Medicine, University of California at San Diego, La Jolla, USA
| | - Veeral Ajmera
- Division of Gastroenterology and Hepatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA; NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, USA.
| | - Monica Guma
- Department of Rheumatology, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093, USA; Department of Medicine, Autonomous University of Barcelona, Plaça Cívica, 08193 Bellaterra, Barcelona, Spain; San Diego VA Healthcare Service, San Diego, CA, 92161, USA.
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15
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Konen FF, Möhn N, Witte T, Schefzyk M, Wiestler M, Lovric S, Hufendiek K, Schwenkenbecher P, Sühs KW, Friese MA, Klotz L, Pul R, Pawlitzki M, Hagin D, Kleinschnitz C, Meuth SG, Skripuletz T. Treatment of autoimmunity: The impact of disease-modifying therapies in multiple sclerosis and comorbid autoimmune disorders. Autoimmun Rev 2023; 22:103312. [PMID: 36924922 DOI: 10.1016/j.autrev.2023.103312] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 03/09/2023] [Indexed: 03/17/2023]
Abstract
More than 10 disease-modifying therapies (DMT) are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of multiple sclerosis (MS) and new therapeutic options are on the horizon. Due to different underlying therapeutic mechanisms, a more individualized selection of DMTs in MS is possible, taking into account the patient's current situation. Therefore, concomitant treatment of various comorbid conditions, including autoimmune mediated disorders such as rheumatoid arthritis, should be considered in MS patients. Because the pathomechanisms of autoimmunity partially overlap, DMT could also treat concomitant inflammatory diseases and simplify the patient's treatment. In contrast, the exacerbation and even new occurrence of several autoimmune diseases have been reported as a result of immunomodulatory treatment of MS. To simplify treatment and avoid disease exacerbation, knowledge of the beneficial and adverse effects of DMT in other autoimmune disorders is critical. Therefore, we conducted a literature search and described the beneficial and adverse effects of approved and currently studied DMT in a large number of comorbid autoimmune diseases, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, cutaneous disorders including psoriasis, Sjögren´s syndrome, systemic lupus erythematosus, systemic vasculitis, autoimmune hepatitis, and ocular autoimmune disorders. Our review aims to facilitate the selection of an appropriate DMT in patients with MS and comorbid autoimmune diseases.
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Affiliation(s)
- Franz Felix Konen
- Department of Neurology, Hannover Medical School, 30625 Hannover, Germany..
| | - Nora Möhn
- Department of Neurology, Hannover Medical School, 30625 Hannover, Germany..
| | - Torsten Witte
- Department of Rheumatology and Clinical Immunology, Hannover Medical School, 30625 Hannover, Germany..
| | - Matthias Schefzyk
- Department of Dermatology, Allergology and Venerology, Hannover Medical School, 30625 Hannover, Germany..
| | - Miriam Wiestler
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
| | - Svjetlana Lovric
- Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany.
| | - Karsten Hufendiek
- University Eye Hospital, Hannover Medical School, 30625 Hannover, Germany.
| | | | - Kurt-Wolfram Sühs
- Department of Neurology, Hannover Medical School, 30625 Hannover, Germany..
| | - Manuel A Friese
- Institute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany.
| | - Luisa Klotz
- Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149 Muenster, Germany.
| | - Refik Pul
- Department of Neurology, University Medicine Essen, Essen, Germany; Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, Essen 45147, Germany.
| | - Marc Pawlitzki
- Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany.
| | - David Hagin
- Allergy and Clinical Immunology Unit, Department of Medicine, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, University of Tel Aviv, 6 Weizmann St., Tel-Aviv 6423906, Israel.
| | - Christoph Kleinschnitz
- Department of Neurology, University Medicine Essen, Essen, Germany; Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, Essen 45147, Germany.
| | - Sven G Meuth
- Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany.
| | - Thomas Skripuletz
- Department of Neurology, Hannover Medical School, 30625 Hannover, Germany..
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16
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Dauth S, Klippstein M, Köhm M. [Psoriatic arthritis : Clinical challenges and pharmaceutical management]. Z Rheumatol 2023; 82:220-232. [PMID: 36856805 DOI: 10.1007/s00393-023-01326-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2023] [Indexed: 03/02/2023]
Abstract
Psoriatic arthritis (PsA) is a systemic immune-mediated inflammatory disease of the musculoskeletal system, which is accompanied by a chronic and progressive course. It is characterized by different clinical manifestations and can severely impair the quality of life and function of patients due to the existing heterogeneity of the manifestations. The (early) diagnosis of PsA and individualized therapeutic management in routine clinical practice are difficult due to the enormous clinical variability. In addition to the appearance of arthritis of the peripheral joints, there can be involvement of the axial skeleton, skin psoriasis, nail psoriasis, enthesitis and dactylitis. The clinical appearance, course of the disease, risk factors and pathophysiological mechanisms of PsA have been extensively researched in recent decades. With the associated better understanding of the disease, new treatment options and goals for effective treatment have also been established.
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Affiliation(s)
- Stephanie Dauth
- Fraunhofer-Institut für Translationale Medizin und Pharmakologie (ITMP), Frankfurt/Main, Deutschland
- Fraunhofer Exzellenzcluster für Immunmediierte Erkrankungen (CIMD), Frankfurt/Main, Deutschland
| | - Maximilian Klippstein
- Fraunhofer-Institut für Translationale Medizin und Pharmakologie (ITMP), Frankfurt/Main, Deutschland
- Fraunhofer Exzellenzcluster für Immunmediierte Erkrankungen (CIMD), Frankfurt/Main, Deutschland
| | - Michaela Köhm
- Fraunhofer-Institut für Translationale Medizin und Pharmakologie (ITMP), Frankfurt/Main, Deutschland.
- Fraunhofer Exzellenzcluster für Immunmediierte Erkrankungen (CIMD), Frankfurt/Main, Deutschland.
- Abteilung Rheumatologie, Goethe-Universität Frankfurt/Main, Theodor-Stern-Kai 7, 60596, Frankfurt/Main, Deutschland.
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17
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Zheng K, Chen Y, Liu S, He C, Yang Y, Wu D, Wang L, Li M, Zeng X, Zhang F. Leflunomide: Traditional immunosuppressant with concurrent antiviral effects. Int J Rheum Dis 2023; 26:195-209. [PMID: 36371788 DOI: 10.1111/1756-185x.14491] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 10/06/2022] [Accepted: 10/24/2022] [Indexed: 11/15/2022]
Abstract
Leflunomide is a classic disease-modifying anti-rheumatic drug that is widely used to treat autoimmune diseases. Studies also show its antiviral effects in in vitro and/or in vivo experiments. Considering glucocorticoids, immunosuppressants and newly emerged antibodies commonly used in autoimmune diseases and autoinflammatory disorders bring risk of infection such as viral infection, leflunomide with combination of anti-viral and immunosuppressive features to maintain the balance between infection and anti-inflammation are attractive. Here we summarize the actions and mechanisms of leflunomide in immunoregulatory and antiviral effects.
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Affiliation(s)
- Kunyu Zheng
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital (PUMCH), Beijing, China
| | - Yiran Chen
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital (PUMCH), Beijing, China
| | - Suying Liu
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital (PUMCH), Beijing, China
| | - Chengmei He
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital (PUMCH), Beijing, China
| | - Yunjiao Yang
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital (PUMCH), Beijing, China
| | - Di Wu
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital (PUMCH), Beijing, China
| | - Li Wang
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital (PUMCH), Beijing, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital (PUMCH), Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital (PUMCH), Beijing, China
| | - Fengchun Zhang
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital (PUMCH), Beijing, China
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18
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Maślanka T. Effect of IL-27, Teriflunomide and Retinoic Acid and Their Combinations on CD4 + T Regulatory T Cells-An In Vitro Study. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27238471. [PMID: 36500570 PMCID: PMC9739213 DOI: 10.3390/molecules27238471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 11/22/2022] [Accepted: 11/28/2022] [Indexed: 12/11/2022]
Abstract
The principal goal of the study was to verify the concept of pharmacological induction of Foxp3+CD25+CD4+ T regulatory (Treg) cells which will additionally be characterized by a highly suppressive phenotype, i.e., by extensive CD25 and CD39 expression and IL-10 and TGF-β production. Stimulated and unstimulated murine lymphocytes were exposed to IL-27, teriflunomide (TER), and all trans retinoic acid (ATRA) alone and to their combinations. The study demonstrated that: (a) IL-27 alone induced CD39 expression on Treg cells and the generation of Tr1 cells; (b) TER alone induced Foxp3-expressing CD4+ T cells and up-regulated density of CD25 on these cells; TER also induced the ability of Treg cells to TGF-β production; (c) ATRA alone induced CD39 expression on Treg cells. The experiments revealed a strong superadditive effect between IL-27 and ATRA with respect to increasing CD39 expression on Treg cells. Moreover, IL-27 and ATRA in combination, but not alone, induced the ability of Treg cells to IL-10 production. However, the combination of IL-27, TER, and ATRA did not induce the generation of Treg cell subset with all described above features. This was due to the fact that TER abolished all listed above desired effects induced by IL-27 alone, ATRA alone, and their combination. IL-27 alone, ATRA alone, and their combination affected TER-induced effects to a lesser extent. Therefore, it can be concluded that in the aspect of pharmacological induction of Treg cells with a highly suppressive phenotype, the triple combination treatment with TER, IL-27, and ATRA does not provide any benefits over TER alone or dual combination including IL-27 and ATRA.
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Affiliation(s)
- Tomasz Maślanka
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego Street 13, 10-719 Olsztyn, Poland
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19
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Packham J, Tarar B. An overview of psoriatic arthritis including clinical manifestations, assessment, diagnostic criteria, investigations, drug management and GRAPPA guidelines. Musculoskeletal Care 2022; 20 Suppl 1:S2-S11. [PMID: 36356108 DOI: 10.1002/msc.1693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 08/15/2022] [Indexed: 06/16/2023]
Abstract
Psoriatic arthritis (PsA) is a chronic and often progressive inflammatory disease, occurring in up to 30% of patients with psoriasis. Assessment of patients with PsA requires consideration of all disease domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, psoriatic nail disease, uveitis and inflammatory bowel disease. Co-morbidities and related conditions should all be considered including: obesity, metabolic syndrome, cardiovascular disease, anxiety/depression, liver disease, chronic infections, malignancy, osteoporosis, fibromyalgia and reproductive health.
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Affiliation(s)
- Jonathan Packham
- Haywood Rheumatology Centre, Midlands Partnership NHS Foundation Trust, Staffordshire, UK
- Academic Unit of Population and Lifespan Sciences, University of Nottingham, Nottingham, UK
| | - Bilal Tarar
- Haywood Rheumatology Centre, Midlands Partnership NHS Foundation Trust, Staffordshire, UK
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20
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Alnaqbi KA, Hannawi S, Namas R, Alshehhi W, Badsha H, Al‐Saleh J. Consensus statements for pharmacological management, monitoring of therapies, and comorbidity management of psoriatic arthritis in the United Arab Emirates. Int J Rheum Dis 2022; 25:1107-1122. [PMID: 35916205 PMCID: PMC9804226 DOI: 10.1111/1756-185x.14406] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 06/28/2022] [Accepted: 07/17/2022] [Indexed: 01/05/2023]
Abstract
OBJECTIVE Psoriatic arthritis (PsA), a chronic inflammatory disease characterized by heterogeneous clinical manifestations, substantially impacts the quality of life of affected individuals. This article aims at developing consensus recommendations for the management of PsA and associated comorbidities and screening and monitoring requirements of PsA therapies in the United Arab Emirates (UAE) population. METHODS An extensive review of present international and regional guidelines and publications on the pharmacological management, monitoring of therapies in the context of PsA was performed. Key findings from guidelines and literature were reviewed by a panel of experts from the UAE at several meetings to align with current clinical practices. Consensus statements were formulated based on collective agreement of the experts and members of Emirates Society for Rheumatology. RESULTS The consensus recommendations were developed to aid practitioners in clinical decision-making with respect to dosage recommendations for pharmacological therapies for PsA, including conventional drugs, non-biologic, and biologic therapies. Consensus recommendations for therapeutic options for the treatment of PsA domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, psoriasis, and nail disease, were developed. The panel emphasized the importance of monitoring PsA therapies and arrived at a consensus on monitoring requirements for PsA therapies. The expert panel proposed recommendations for the management of common comorbidities associated with PsA. CONCLUSION These consensus recommendations can guide physicians and healthcare professionals in the UAE in making proper treatment decisions, as well as efficiently managing comorbidities and monitoring therapies in patients with PsA.
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Affiliation(s)
- Khalid A. Alnaqbi
- Department of RheumatologyTawam HospitalAl AinUAE
- College of Medicine and Health SciencesUAE UniversityAl AinUAE
| | - Suad Hannawi
- Emirates Health Services (EHS)DubaiUAE
- Ministry of Health and PreventionDubaiUAE
| | - Rajaie Namas
- Division of Rheumatology, Department of Internal MedicineCleveland Clinic Abu DhabiUAE
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21
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Alnaqbi KA, Hannawi S, Namas R, Alshehhi W, Badsha H, Al‐Saleh J. Consensus statements for evaluation and nonpharmacological Management of Psoriatic Arthritis in UAE. Int J Rheum Dis 2022; 25:725-732. [PMID: 35678066 PMCID: PMC9544782 DOI: 10.1111/1756-185x.14357] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 03/23/2022] [Accepted: 05/17/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Psoriatic arthritis (PsA), a chronic inflammatory arthropathy, is often underdiagnosed in Middle Eastern countries, substantially impacting the treatment of affected individuals. This article aims to highlight current unmet clinical needs and provide consensus recommendations for region-specific evaluation methods and nonpharmacological therapies in the United Arab Emirates (UAE). METHOD An extensive literature review was conducted, focusing especially on global and regional guidelines for the evaluation and treatment of PsA. These form the basis of the consensus statements formulated. Additionally, an expert panel of key opinion leaders from the UAE reviewed these guidelines and available literature at an advisory board meeting to identify unmet needs, bridge clinical gaps in the UAE, and develop consensus statements for the evaluation and treatment of PsA. RESULT The consensus statements were developed based on overarching principles for the management of PsA, evaluation of patients with PsA, and nonpharmacological approaches for the management of PsA. The overarching principles included adopting a targeted, multidisciplinary approach, along with collaboration between rheumatologists and dermatologists in cases of clinically significant skin involvement. The panel also highlighted the value of composite disease severity measures for characterizing clinical manifestations of PsA. In terms of nonpharmacological management approaches, lifestyle modification (comprising dietary change, exercise, and cessation of smoking) and psychotherapy were recommended. CONCLUSION The consensus statements will aid healthcare professionals in clinical decision-making in the context of PsA.
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Affiliation(s)
- Khalid A. Alnaqbi
- Department of RheumatologyTawam HospitalAl AinUAE
- College of Medicine and Health SciencesUAE UniversityAl AinUAE
| | - Suad Hannawi
- Emirates Health Services (EHS)DubaiUAE
- Ministry of Health and PreventionDubaiUAE
| | - Rajaie Namas
- Division of Rheumatology, Department of Internal MedicineCleveland ClinicAbu DhabiUAE
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22
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Efficacy and safety of tofacitinib versus leflunomide with glucocorticoids treatment in Takayasu arteritis: A prospective study. Semin Arthritis Rheum 2022; 55:152018. [PMID: 35523066 DOI: 10.1016/j.semarthrit.2022.152018] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 04/05/2022] [Accepted: 04/25/2022] [Indexed: 12/25/2022]
Abstract
To investigate the efficacy and safety of leflunomide (LEF) versus tofacitinib (TOF) in Takayasu arteritis (TAK) patients. Sixty-seven active patients were recruited from an ongoing observational TAK cohort, including 35 patients treated with glucocorticoids (GCs) and LEF and 32 patients treated with GCs and TOF. The observation period was 12 months. The effectiveness rate (ER), remission rate, inflammatory parameters reduction, vascular imaging changes, GCs tapering, disease relapse and side-effects were evaluated between two groups. These aspects were also assessed separately among treatment-naïve or -refractory patients. The ER at 6 and 12 months was 88.57% (31/35) vs. 87.50% (28/32) (p = 1.00) and 71.43% (25/35) vs. 71.88% (23/32) (p = 1.00) in the LEF and TOF group. The percentage of patients with persistent remission from 6th to 12th months and GCs≤7.5 mg/day at 12 months was higher in TOF group (15 (46.88%) vs. 6 (17.14%) p = 0.02). The relapse prevalence was 6 (17.14%) and 7 (21.88%) (p = 0.76), respectively. Erythrocyte sedimentation rate (ESR) was decreased significantly at 6 months in both groups (p<0.05), whereas C-reactive protein (CRP) level was reduced significantly at 6 months only in the TOF group (p = 0.007). The proportion of patients with imaging improvement was higher in the TOF group (eight (25.00%) and two (5.71%), p = 0.04). Side-effect prevalence was higher in the LEF group (11 (31.43%) vs. 3 (9.38%), p = 0.04). In conclusion, LEF and TOF were comparable for TAK treatment. TOF might be a potential agent to maintain disease remission at a low dose of glucocorticoids in TAK.
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23
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Zheng Y, Li S, Song K, Ye J, Li W, Zhong Y, Feng Z, Liang S, Cai Z, Xu K. A Broad Antiviral Strategy: Inhibitors of Human DHODH Pave the Way for Host-Targeting Antivirals against Emerging and Re-Emerging Viruses. Viruses 2022; 14:v14050928. [PMID: 35632670 PMCID: PMC9146014 DOI: 10.3390/v14050928] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/25/2022] [Accepted: 04/25/2022] [Indexed: 12/30/2022] Open
Abstract
New strategies to rapidly develop broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses. Host-targeting antivirals (HTAs) that target the universal host factors necessary for viral replication are the most promising approach, with broad-spectrum, foresighted function, and low resistance. We and others recently identified that host dihydroorotate dehydrogenase (DHODH) is one of the universal host factors essential for the replication of many acute-infectious viruses. DHODH is a rate-limiting enzyme catalyzing the fourth step in de novo pyrimidine synthesis. Therefore, it has also been developed as a therapeutic target for many diseases relying on cellular pyrimidine resources, such as cancers, autoimmune diseases, and viral or bacterial infections. Significantly, the successful use of DHODH inhibitors (DHODHi) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection further supports the application prospects. This review focuses on the advantages of HTAs and the antiviral effects of DHODHi with clinical applications. The multiple functions of DHODHi in inhibiting viral replication, stimulating ISGs expression, and suppressing cytokine storms make DHODHi a potent strategy against viral infection.
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Affiliation(s)
- Yucheng Zheng
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; (Y.Z.); (K.S.); (J.Y.); (W.L.); (Y.Z.); (S.L.); (Z.C.)
| | - Shiliang Li
- State Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (S.L.); (Z.F.)
| | - Kun Song
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; (Y.Z.); (K.S.); (J.Y.); (W.L.); (Y.Z.); (S.L.); (Z.C.)
| | - Jiajie Ye
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; (Y.Z.); (K.S.); (J.Y.); (W.L.); (Y.Z.); (S.L.); (Z.C.)
| | - Wenkang Li
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; (Y.Z.); (K.S.); (J.Y.); (W.L.); (Y.Z.); (S.L.); (Z.C.)
| | - Yifan Zhong
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; (Y.Z.); (K.S.); (J.Y.); (W.L.); (Y.Z.); (S.L.); (Z.C.)
| | - Ziyan Feng
- State Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (S.L.); (Z.F.)
| | - Simeng Liang
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; (Y.Z.); (K.S.); (J.Y.); (W.L.); (Y.Z.); (S.L.); (Z.C.)
| | - Zeng Cai
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; (Y.Z.); (K.S.); (J.Y.); (W.L.); (Y.Z.); (S.L.); (Z.C.)
- Institute for Vaccine Research, Animal Biosafety Level 3 Laboratory at Center for Animal Experiments, Wuhan University, Wuhan 430072, China
| | - Ke Xu
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; (Y.Z.); (K.S.); (J.Y.); (W.L.); (Y.Z.); (S.L.); (Z.C.)
- Institute for Vaccine Research, Animal Biosafety Level 3 Laboratory at Center for Animal Experiments, Wuhan University, Wuhan 430072, China
- Correspondence: ; Tel.: +86-27-68756997; Fax: +86-27-68754592
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Hioki T, Komine M, Ohtsuki M. Diagnosis and Intervention in Early Psoriatic Arthritis. J Clin Med 2022; 11:jcm11072051. [PMID: 35407659 PMCID: PMC8999837 DOI: 10.3390/jcm11072051] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/19/2022] [Accepted: 03/29/2022] [Indexed: 02/05/2023] Open
Abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disorder that affects approximately 20–30% of patients with psoriasis. PsA causes deformities and joint damage, impairing quality of life and causing long-term functional disability. Several recent studies demonstrated that early diagnosis and intervention for PsA prevents permanent invalidity. However, the clinical features of PsA vary and are shared with other differential diseases, such as reactive arthritis, osteoarthritis, and ankylosing spondylitis. The common and overlapping features among these diseases complicate the accurate early diagnosis and intervention of PsA. Therefore, this review focuses on the current knowledge of the diagnosis of early PsA and discusses the meaning of early intervention for early PsA.
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Affiliation(s)
- Tomoyuki Hioki
- Department of Dermatology, Central Japan International Medical Center, Minokamo 505-8510, Japan
- Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke 329-0498, Japan;
- Correspondence: (T.H.); (M.K.)
| | - Mayumi Komine
- Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke 329-0498, Japan;
- Correspondence: (T.H.); (M.K.)
| | - Mamitaro Ohtsuki
- Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke 329-0498, Japan;
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25
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Tofacitinib combined with leflunomide for treatment of psoriatic arthritis with IgA nephropathy: a case report with literature review. Clin Rheumatol 2022; 41:2225-2231. [PMID: 35192086 DOI: 10.1007/s10067-022-06113-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 11/03/2022]
Abstract
Psoriasis is a systemic inflammatory disease that is associated with increased risk of several diseases, such as psoriatic arthritis (PsA), inflammatory bowel disease, and cardiovascular diseases. About 20 to 30% patients with psoriasis subsequently develop PsA. IgA nephropathy is the most common primary glomerular disease world-wide. Psoriasis and IgA nephropathy appear to be associated, but the mechanism underlying this connection is unclear. Tofacitinib and leflunomide are common treatments for psoriatic arthritis. We administered tofacitinib combined with leflunomide to a 38-year-old female patient who presented with PsA and IgA nephropathy. After treatment, she experienced significant reductions in the psoriatic lesions, pain in the right knee joint, and proteinuria. Administration of tofacitinib combined with leflunomide for treatment of a patient who had PsA complicated with IgA nephropathy led to significant resolution of the symptoms of both conditions. These results suggest similarities in the pathogenesis of PsA and IgA nephropathy and a possible new treatment for IgA nephropathy.
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26
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Carneiro S, Palominos PE, Anti SMA, Assad RL, Gonçalves RSG, Chiereghin A, Lyrio AM, Ximenes AC, Saad CG, Gonçalves CR, Kohem CL, Marques CDL, Schainberg CG, de Souza Meirelles E, Resende GG, Pieruccetti LB, Keiserman MW, Yazbek MA, Sampaio-Barros PD, da Cruz Lage R, Bonfiglioli R, Oliveira TL, Azevedo VF, Bianchi WA, Bernardo WM, Dos Santos Simões R, de Medeiros Pinheiro M, Campanholo CB. Brazilian Society of Rheumatology 2020 guidelines for psoriatic arthritis. Adv Rheumatol 2021; 61:69. [PMID: 34819174 DOI: 10.1186/s42358-021-00219-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 09/28/2021] [Indexed: 12/29/2022] Open
Abstract
Psoriatic arthritis (PsA) is a chronic and systemic immune disease characterized by inflammation of peripheral and/or axial joints and entheses in patients with psoriasis (PsO). Extra-articular and extracutaneous manifestations and numerous comorbidities can also be present. These recommendations replace the previous version published in May 2013. A systematic review of the literature retrieved 191 articles that were used to formulate 12 recommendations in response to 12 clinical questions, divided into 4 sections: diagnosis, non-pharmacological treatment, conventional drug therapy and biologic therapy. These guidelines provide evidence-based information on the clinical management for PsA patients. For each recommendation, the level of evidence (highest available), degree of strength (Oxford) and degree of expert agreement (interrater reliability) are reported.
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Affiliation(s)
- Sueli Carneiro
- Universidade Federal do Rio de Janeiro (UFRJ), Rua Farme de Amoedo, 140/601. Ipanema, Rio de Janeiro, RJ, CEP 22420-020, Brazil.
| | | | | | | | | | | | - Andre Marun Lyrio
- Pontifícia Universidade Católica de Campinas (PUC), Campinas, Brazil
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Neema S, Sandhu S, Gupta A, Jagadeesan S, Vasudevan B. Unconventional treatment options in psoriasis: A review. Indian J Dermatol Venereol Leprol 2021; 88:137-143. [PMID: 34623042 DOI: 10.25259/ijdvl_22_2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 05/01/2021] [Indexed: 11/04/2022]
Abstract
Psoriasis is a common skin disease that affects 1-3% of the general population. The treatment depends on body surface area involved, quality of life impairment and associated comorbidities. The treatment options include topical therapy, phototherapy, conventional systemic therapy (methotrexate, cyclosporine and acitretin), biologics and oral small molecules (apremilast and tofacitinib). Despite the availability of newer therapies such as biologics and oral small molecules, many a time, there is a paucity of treatment options due to the chronic nature of the disease, end-organ toxicity of the conventional drugs or high cost of newer drugs. In these scenarios, unconventional treatment options may be utilized as stand-alone or adjuvant therapy. In this review, we have discussed these uncommonly used treatment options in the management of psoriasis.
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Affiliation(s)
- Shekhar Neema
- Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India
| | - Sunmeet Sandhu
- Department of Dermatology, Command Hospital Air Force, Bengaluru, Karnataka, India
| | - Ankan Gupta
- Department of Dermatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Soumya Jagadeesan
- Department of Dermatology, Amrita Institute of Medical Sciences, Cochin, Kerala, India
| | - Biju Vasudevan
- Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India
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28
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Brummer T, Ruck T, Meuth SG, Zipp F, Bittner S. Treatment approaches to patients with multiple sclerosis and coexisting autoimmune disorders. Ther Adv Neurol Disord 2021; 14:17562864211035542. [PMID: 34457039 PMCID: PMC8388232 DOI: 10.1177/17562864211035542] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 07/08/2021] [Indexed: 12/30/2022] Open
Abstract
The past decades have yielded major therapeutic advances in many autoimmune conditions - such as multiple sclerosis (MS) - and thus ushered in a new era of more targeted and increasingly potent immunotherapies. Yet this growing arsenal of therapeutic immune interventions has also rendered therapy much more challenging for the attending physician, especially when treating patients with more than one autoimmune condition. Importantly, some therapeutic strategies are either approved for several autoimmune disorders or may be repurposed for other conditions, therefore opening new curative possibilities in related fields. In this article, we especially focus on frequent and therapeutically relevant concomitant autoimmune conditions faced by neurologists when treating patients with MS, namely psoriasis, rheumatoid arthritis and inflammatory bowel diseases. We provide an overview of the available disease-modifying therapies, highlight possible contraindications, show pathophysiological overlaps and finally present which therapeutics can be utilized as a combinatory treatment, in order to 'kill two birds with one stone'.
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Affiliation(s)
- Tobias Brummer
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Tobias Ruck
- Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Sven G. Meuth
- Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Frauke Zipp
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Stefan Bittner
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Rhineland-Palatinate, Mainz 55131, Germany
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Abstract
Psoriatic arthritis (PsA) is a complex inflammatory disease with heterogeneous clinical features, which complicates psoriasis in 30% of patients. There are no diagnostic criteria or tests available. Diagnosis is most commonly made by identifying inflammatory musculoskeletal features in joints, entheses or the spine in the presence of skin and/or nail psoriasis and in the usual absence of rheumatoid factor and anti-cyclic citrullinated peptide. The evolution of psoriasis to PsA may occur in stages, although the mechanisms are unclear. In many patients, there may be little or no relationship between severity of musculoskeletal inflammation and severity of skin or nail psoriasis. The reason for this disease heterogeneity may be explained by differences in genotype, especially in the HLA region. New targeted therapies for PsA have been approved with additional therapies in development. These developments have substantially improved both short-term and long-term outcomes including a reduction in musculoskeletal and skin manifestations and in radiographic damage. With efforts underway aimed at improving our understanding of the molecular basis for the heterogeneity of PsA, a personalized approach to treating PsA may become possible.
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30
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Keeling S, Maksymowych WP. JAK inhibitors, psoriatic arthritis, and axial spondyloarthritis: a critical review of clinical trials. Expert Rev Clin Immunol 2021; 17:701-715. [PMID: 33944642 DOI: 10.1080/1744666x.2021.1925541] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Psoriatic arthritis (PsA) and spondyloarthritis (SpA) are inflammatory arthritides associated with progressive damage, deformity and morbidity. Janus kinase (JAK) inhibitors block JAKs, cytoplasmic protein tyrosine kinases important in signal transduction and immune processes that are currently being studied as synthetic disease modifying anti-rheumatic drugs (tsDMARDs) in psoriatic arthritis and spondyloarthritis. AREAS COVERED This review evaluates published phase 2 and 3 clinical trial data for JAK kinase inhibitors for psoriatic arthritis and spondyloarthritis. A literature search using PubMed was conducted using the following keywords: 'psoriatic arthritis', 'ankylosing spondylitis', 'axial spondyloarthritis', 'non-radiographic axial spondyloarthritis', 'tofacitinib', 'baricitinib', 'filgotinib' and 'upadacitinib'. Mechanism of action, phase 2 and 3 clinical trial data, including efficacy and safety, are discussed. EXPERT OPINION JAK inhibitors are important orally administered agents conferring different degrees of selectivity toward JAK1, JAK2, and JAK3 which may have implications on efficacy and safety in PsA and SpA. Phase 2 and 3 clinical trials in PsA for tofacitinib and upadacitinib and phase 2 for filgotinib confirmed efficacy comparable to biologic DMARDs. In SpA, phase 2 and 2/3 studies confirmed significant efficacy of tofacitinib, filgotinib and upadacitinib compared to placebo. Safety was comparable to clinical trial, long-term extension, and registry data for rheumatoid arthritis.
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Affiliation(s)
- Stephanie Keeling
- Division of Rheumatology, University of Alberta, Edmonton, Alberta, Canada
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31
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Management of particular clinical situations in psoriatic arthritis: an expert's recommendation document based on systematic literature review and extended Delphi process. Rheumatol Int 2021; 41:1549-1565. [PMID: 33934175 PMCID: PMC8316175 DOI: 10.1007/s00296-021-04877-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 04/23/2021] [Indexed: 02/07/2023]
Abstract
To establish practical recommendations for the management of patients with psoriatic arthritis (PsA) with particular clinical situations that might lead to doubts in the pharmacological decision-making. A group of six expert rheumatologists on PsA identified particular clinical situations in PsA. Then, a systematic literature review (SLR) was performed to analyse the efficacy and safety of csDMARDs, b/tsDMARDs in PsA. In a nominal group meeting, the results of the SLR were discussed and a set of recommendations were proposed for a Delphi process. A total of 65 rheumatologists were invited to participate in the Delphi. Agreement was defined if ≥ 70% of the participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grade of recommendation was established based on the Oxford Evidence-Based Medicine categorisation. Particular clinical situations included monoarthritis, axial disease, or non-musculoskeletal manifestations. The SLR finally comprised 131 articles. A total of 16 recommendations were generated, all but 1 reached consensus. According to them, it is crucial to carefully analyse the impact of individual manifestations on patients (disability, quality of life, etc.), but also to recognise the impact of each drug singularities on selected clinical phenotypes to adopt the most appropriate treatment strategy. Early diagnosis and treatment to target approach, along with a close risk management, is also necessary. These recommendations are intended to complement gaps in national and international guidelines by helping health professionals address and manage particular clinical situations in PsA.
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32
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Ayan G, Aydin SZ, Kimyon G, Ozisler C, Tinazzi I, Dogru A, Omma A, Kilic L, Yılmaz S, Kucuksahin O, Gönüllü E, Yıldız F, Can M, Balkarlı A, Solmaz D, Dalkılıc E, Bayindir O, Yıldırım Çetin G, Ergulu Esmen S, Ersozlu ED, Duruoz MT, Akyol L, Kucuk A, Bes C, Cınar M, Erden A, Mercan R, Bakirci S, Kasifoglu T, Yazısız V, Kalyoncu U. PsART-ID inception cohort: clinical characteristics, treatment choices and outcomes of patients with psoriatic arthritis. Rheumatology (Oxford) 2021; 60:1755-1762. [PMID: 33097960 DOI: 10.1093/rheumatology/keaa663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 09/04/2020] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVES Our aim is to understand clinical characteristics, real-life treatment strategies, outcomes of early PsA patients and determine the differences between the inception and established PsA cohorts. METHODS PsArt-ID (Psoriatic Arthritis- International Database) is a multicentre registry. From that registry, patients with a diagnosis of PsA up to 6 months were classified as the inception cohort (n==388). Two periods were identified for the established cohort: Patients with PsA diagnosis within 5-10 years (n = 328), ≥10 years (n = 326). Demographic, clinical characteristics, treatment strategies, outcomes were determined for the inception cohort and compared with the established cohorts. RESULTS The mean (s.d.) age of the inception cohort was 44.7 (13.3) and 167/388 (43.0%) of the patients were male. Polyarticular and mono-oligoarticular presentations were comparable in the inception and established cohorts. Axial involvement rate was higher in the cohort of patients with PsA ≥10 years compared with the inception cohort (34.8% vs 27.7%). As well as dactylitis and nail involvement (P = 0.004, P = 0.001 respectively). Both enthesitis, deformity rates were lower in the inception cohort. Overall, 13% of patients in the inception group had a deformity. MTX was the most commonly prescribed treatment for all cohorts with 10.7% of the early PsA patients were given anti-TNF agents after 16 months. CONCLUSION The real-life experience in PsA patients showed no significant differences in the disease pattern rates except for the axial involvement. The dactylitis, nail involvement rates had increased significantly after 10 years from the diagnosis and the enthesitis, deformity had an increasing trend over time.
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Affiliation(s)
- Gizem Ayan
- Faculty of Medicine, Rheumatology, University of Ottawa, Ottawa, ON, Canada.,Department of Internal Medicine, Division of Rheumatology Ankara, Faculty of Medicine, Hacettepe University, Turkey
| | - Sibel Zehra Aydin
- Faculty of Medicine, Rheumatology, University of Ottawa, Ottawa, ON, Canada.,The Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Gezmis Kimyon
- Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Mustafa Kemal University, Hatay, Turkey
| | - Cem Ozisler
- Department of Internal Medicine, Division of Rheumatology, Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey
| | - Ilaria Tinazzi
- Sacro Cuore Don Calabria Hospital, Unit of Rheumatology, Negrar-Verona, VR, Italy
| | - Atalay Dogru
- Department of Internal Medicine, Division of Rheumatology, Suleyman Demirel University Faculty of Medicine, Isparta, Turkey
| | - Ahmet Omma
- Department of Internal Medicine, Division of Rheumatology, Ankara Numune Education and Research Hospital, Ankara, Turkey
| | - Levent Kilic
- Department of Internal Medicine, Division of Rheumatology Ankara, Faculty of Medicine, Hacettepe University, Turkey
| | - Sema Yılmaz
- Department of Internal Medicine, Division of Rheumatology, Faculty of Medicine, Selcuk University, Konya, Turkey
| | - Orhan Kucuksahin
- Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Ankara Yildirim Beyazit University, Ankara, Turkey
| | - Emel Gönüllü
- Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Sakarya University, Sakarya, Turkey
| | - Fatih Yıldız
- Department of Internal Medicine, Division of Rheumatology, Van Training and Research Hospital, University of Health Sciences, Turkey
| | - Meryem Can
- Department of Internal Medicine, Division of Rheumatology, Faculty of Medicine, Medipol University, Istanbul, Turkey
| | - Ayşe Balkarlı
- Department of Internal Medicine, Division of Rheumatology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Dilek Solmaz
- Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Izmir Katip Celebi University, Izmir, Turkey
| | - Ediz Dalkılıc
- Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Uludag University, Bursa, Turkey
| | - Ozun Bayindir
- Department of Internal Medicine, Division of Rheumatology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Gözde Yıldırım Çetin
- Department of Internal Medicine, Division of Rheumatology, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey
| | - Serpil Ergulu Esmen
- Department of Internal Medicine, Division of Rheumatology, Konya Education and Research Hospital, Konya, Turkey
| | - Emine Duygu Ersozlu
- Department of Internal Medicine, Division of Rheumatology, Adana Numune Training and Research Hospital, Adana, Turkey
| | - Mehmet Tuncay Duruoz
- Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Division of Rheumatology, Marmara University, Istanbul, Turkey
| | - Lütfi Akyol
- Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Ondokuz Mayis University, Samsun, Turkey
| | - Adem Kucuk
- Meram Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Necmettin Erbakan Univeristy, Konya, Turkey
| | - Cemal Bes
- Department of Internal Medicine, Division of Rheumatology, and Research Hospital, University of Health Sciences Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Muhammet Cınar
- Department of Internal Medicine, Division of Rheumatology, Gülhane Training and Research Hospital, Ankara, Turkey
| | - Abdulsamet Erden
- Department of Internal Medicine, Division of Rheumatology Ankara, Faculty of Medicine, Hacettepe University, Turkey
| | - Rıdvan Mercan
- Department of Internal Medicine, Division of Rheumatology Tekirdag, Faculty of Medicine, Namık Kemal University, Turkey
| | - Sibel Bakirci
- Department of Internal Medicine, Division of Rheumatology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Timucin Kasifoglu
- Department of Internal Medicine, Division of Rheumatology, Faculty of Medicine, Osmangazi University, Eskisehir, Turkey
| | - Veli Yazısız
- Department of Internal Medicine, Division of Rheumatology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
| | - Umut Kalyoncu
- Department of Internal Medicine, Division of Rheumatology Ankara, Faculty of Medicine, Hacettepe University, Turkey
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Tsai TF, Hsieh TY, Chi CC, Chou CT, Hsieh LF, Chen HH, Hui RCY, Lee CH, Liu CH, Liu HC, Yeo KJ, Chen CH, Chen HA, Chen YC, Chen YJ, Chiu HY, Ho JC, Huang YH, Lai PJ, Lee WR, Liao HT, Lin SH, Tseng JC, Wang TS, Wu NL, Yang DH, Tsai WC, Wei JCC. Recommendations for psoriatic arthritis management: A joint position paper of the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology. J Formos Med Assoc 2021; 120:926-938. [PMID: 33012636 DOI: 10.1016/j.jfma.2020.08.026] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 05/25/2020] [Accepted: 08/18/2020] [Indexed: 01/14/2023] Open
Abstract
In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.
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Affiliation(s)
- Tsen-Fang Tsai
- Department of Dermatology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Tsu-Yi Hsieh
- Division of Allergy-Immunology-Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan; Program of Business, College of Business, Feng Chia University, Taichung, Taiwan
| | - Ching-Chi Chi
- Department of Dermatology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chung-Tei Chou
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Lin-Fen Hsieh
- Department of Physical Medicine and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Hsin-Hua Chen
- Division of Allergy-Immunology-Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Rosaline Chung-Yee Hui
- Department of Dermatology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital-Keelung, Keelung, Taiwan
| | - Chih-Hung Lee
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chin-Hsiu Liu
- Division of Allergy, Immunology and Rheumatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Hwa-Chang Liu
- Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan; Department of Orthopedics Surgery, Taiwan Adventist Hospital, Taipei, Taiwan
| | - Kai-Jieh Yeo
- Division of Rheumatology and Immunology, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Hsiung Chen
- Division of Allergy, Immunology and Rheumatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Hung-An Chen
- Department of Allergy, Immunology, and Rheumatology, Chi Mei Medical Center, Tainan, Taiwan
| | - Ying-Chou Chen
- Department of Rheumatology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Ju Chen
- Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Hsien-Yi Chiu
- Department of Dermatology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan; Department of Dermatology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Ji-Chen Ho
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital-Chiayi, Chiayi, Taiwan
| | - Yu-Huei Huang
- Department of Dermatology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Po-Ju Lai
- Division of Dermatology, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Woan-Ruoh Lee
- Department of Dermatology, Taipei Medical University Shuang Ho Hospital, Taipei, Taiwan; Department of Dermatology, School of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Science, Taipei Medical University, Taipei, Taiwan
| | - Hsien-Tzung Liao
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Shang-Hung Lin
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jui-Cheng Tseng
- Division of Allergy, Immunology, and Rheumatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ting-Shun Wang
- Department of Dermatology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan; Division of Dermatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Department of Dermatology, Chung Shan Medical University, Taichung, Taiwan
| | - Nan-Lin Wu
- Department of Dermatology, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
| | - Deng-Ho Yang
- Division of Rheumatology/Immunology/Allergy, Department of Internal Medicine, Taichung Armed-Forces General Hospital, Taichung, Taiwan; Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan; Division of Rheumatology/Immunology/Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wen-Chan Tsai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - James Cheng-Chung Wei
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
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Jacobs ME, Pouw JN, Welsing P, Radstake TRDJ, Leijten EFA. First-line csDMARD monotherapy drug retention in psoriatic arthritis: methotrexate outperforms sulfasalazine. Rheumatology (Oxford) 2021; 60:780-784. [PMID: 32797218 PMCID: PMC7850548 DOI: 10.1093/rheumatology/keaa399] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 05/18/2020] [Indexed: 01/06/2023] Open
Abstract
Objectives Conventional synthetic DMARDs (csDMARDs) are the first-line treatment for PsA, but there is conflicting data regarding their efficacy and scarce reports describing the duration of use (drug retention) of csDMARD in this population. Their position in treatment recommendations is a matter of growing debate due to the availability of alternative treatment options with higher levels of evidence. We aimed to study drug retention and predictors for drug retention among PsA patients receiving first-line csDMARD monotherapy. Methods Retrospective cohort study in DMARD-naïve adult PsA patients in whom a first csDMARD was prescribed as monotherapy primarily to treat PsA-related symptoms. The main outcome was time to failure of the csDMARD (i.e. stopping the csDMARD or adding another DMARD). Results A total of 187 patients were included, who were mainly prescribed MTX (n = 163) or SSZ (n = 21). The pooled median drug retention time was 31.8 months (interquartile range 9.04–110). Drug retention was significantly higher in MTX (median 34.5 months; interquartile range 9.60–123) as compared with SSZ-treated patients (median 12.0 months; interquartile range 4.80– 55.7) (P =0.016, log-rank test). In multivariable Cox regression, the use of MTX and older age were associated with increased retention. The main reasons for treatment failure were inefficacy (52%) and side effects (28%). Upon failure, MTX treated patients were more commonly, subsequently treated with a biologic DMARD compared with SSZ (P < 0.05). Conclusion MTX outperforms SSZ as a first-line csDMARD in DMARD-naïve PsA patients with respect to monotherapy drug retention in daily clinical practice.
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Affiliation(s)
- Marleen E Jacobs
- Department of Rheumatology and Clinical Immunology, Utrecht, the Netherlands.,Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Juliëtte N Pouw
- Department of Rheumatology and Clinical Immunology, Utrecht, the Netherlands.,Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Paco Welsing
- Department of Rheumatology and Clinical Immunology, Utrecht, the Netherlands
| | - Timothy R D J Radstake
- Department of Rheumatology and Clinical Immunology, Utrecht, the Netherlands.,Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Emmerik F A Leijten
- Department of Rheumatology and Clinical Immunology, Utrecht, the Netherlands.,Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
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Papagoras C, Voulgari PV, Drosos AA. Cardiovascular Disease in Spondyloarthritides. Curr Vasc Pharmacol 2020; 18:473-487. [PMID: 31330576 DOI: 10.2174/1570161117666190426164306] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 04/13/2019] [Accepted: 04/13/2019] [Indexed: 12/15/2022]
Abstract
The spondyloarthritides are a group of chronic systemic inflammatory joint diseases, the main types being ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Evidence accumulating during the last decades suggests that patients with AS or PsA carry an increased risk for cardiovascular disease and cardiovascular death. This risk appears to be mediated by systemic inflammation over and above classical cardiovascular risk factors. The excess cardiovascular risk in those patients has been formally acknowledged by scientific organizations, which have called physicians' attention to the matter. The application by Rheumatologists of new effective anti-rheumatic treatments and treat-to-target strategies seems to benefit patients from a cardiovascular point of view, as well. However, more data are needed in order to verify whether anti-rheumatic treatments do have an effect on cardiovascular risk and whether there are differences among them in this regard. Most importantly, a higher level of awareness of the cardiovascular risk is needed among patients and healthcare providers, better tools to recognize at-risk patients and, ultimately, commitment to address in parallel both the musculoskeletal and the cardiovascular aspect of the disease.
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Affiliation(s)
- Charalampos Papagoras
- 1st Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Paraskevi V Voulgari
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
| | - Alexandros A Drosos
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
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Bellinato F, Gisondi P, Girolomoni G. A dermatologist perspective in the pharmacological treatment of patients with psoriasis and psoriatic arthritis. Expert Rev Clin Pharmacol 2020; 13:481-491. [PMID: 32320308 DOI: 10.1080/17512433.2020.1759415] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis in 20-30% of patients. PsA presents as a heterogeneous disease involving different domains and burdened by an important impact on function and quality of life. AREAS COVERED Dermatologists play an important role in the early detection of PsA because in most patients PsA develop after cutaneous psoriasis. The ideal goal of treating patients with PsA is to optimize the controls of symptoms, improve quality of life, and prevent structural damage and disability. The choice of treatment in patients with PsA should take into account also the skin signs and symptoms. Treatment options include NSAIDs, synthetic DMARDSs, anti-TNF-α agents, anti-IL-12/IL-23 agents, anti-IL-17 agents, PDE4 inhibitors, JAK inhibitors, and co-stimulatory blockers. A narrative review based on electronic searches on PubMed® database was performed. Original articles assessing either the role of the dermatologist in the management of PsA and the available treatments for PsA were included. EXPERT OPINION Among different treatments, some drugs show more efficacy in joint signs and symptoms, and poor response on the skin and vice versa. The perspective of the dermatologist in a multidisciplinary setting may provide a helpful tool in the management of patients with PsA.
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Affiliation(s)
- Francesco Bellinato
- Section of Dermatology and Venereology, Department of Medicine, University of Verona , Verona, Italy
| | - Paolo Gisondi
- Section of Dermatology and Venereology, Department of Medicine, University of Verona , Verona, Italy
| | - Giampiero Girolomoni
- Section of Dermatology and Venereology, Department of Medicine, University of Verona , Verona, Italy
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Carron P, De Craemer AS, Van den Bosch F. Peripheral spondyloarthritis: a neglected entity-state of the art. RMD Open 2020; 6:e001136. [PMID: 32385142 PMCID: PMC7299516 DOI: 10.1136/rmdopen-2019-001136] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 04/06/2020] [Accepted: 04/07/2020] [Indexed: 02/06/2023] Open
Abstract
Peripheral spondyloarthritis (pSpA) refers to a number of seemingly different spondyloarthritis subsets in which psoriatic arthritis (PsA) is the most common, and symptoms of arthritis, enthesitis or dactylitis predominate the clinical presentation. Although formal classification criteria for pSpA have been introduced in 2011, only a minority of epidemiological and clinical studies addressed this clinical entity as a separate disease. Moreover, research on outcome measures and treatment modalities in pSpA has been mainly focused on PsA. Subsequently, all biological treatments are off-label in patients with non-psoriatic pSpA. Its neglected status has important implications for clinical practice since the emerging group of early-diagnosed non-psoriatic pSpA patients remains poorly characterised and lacks specific treatment recommendations. This review summarises what is currently known regarding pSpA in terms of epidemiology, clinical presentation, diagnosis and therapeutic approach.
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Affiliation(s)
- Philippe Carron
- Rheumatology, University Hospital Ghent, Ghent, Belgium
- VIB Center for Inflammation Research, Ghent, Belgium
| | - Ann-Sophie De Craemer
- Rheumatology, University Hospital Ghent, Ghent, Belgium
- VIB Center for Inflammation Research, Ghent, Belgium
| | - Filip Van den Bosch
- Rheumatology, University Hospital Ghent, Ghent, Belgium
- VIB Center for Inflammation Research, Ghent, Belgium
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Abstract
Psoriatic arthritis (PsA) is a type of chronic inflammatory arthritis which is associated with psoriasis. The early recognition and treatment for PsA are of critical importance. Janus kinase (JAK) inhibitors, as a kind of orally small molecules, have emerged as an encouraging class of drug in PsA treatment. This review provides a discussion of the role and current status of JAK inhibitors in the control of PsA. There are three JAK inhibitors approved for use in autoimmune diseases, for example, tofacitinib, baricitinib, and upadacitinib, and only tofacitinib has been approved in PsA treatment. The clinical trials of upadacitinib and filgotinib in PsA patients are undergoing. The efficacy and safety of these agents were briefly discussed. Although there are still issues in terms of their efficacy and safety currently, JAK inhibitors are expected to benefit more PsA patients in future.
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Affiliation(s)
- Miao Chen
- Department of Rheumatology & Immunology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
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Landewé R, Ritchlin CT, Aletaha D, Zhang Y, Ganz F, Hojnik M, Coates LC. Inhibition of radiographic progression in psoriatic arthritis by adalimumab independent of the control of clinical disease activity. Rheumatology (Oxford) 2020; 58:1025-1033. [PMID: 30608620 PMCID: PMC6532443 DOI: 10.1093/rheumatology/key417] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 11/03/2018] [Indexed: 12/15/2022] Open
Abstract
Objectives To evaluate the relationship between radiographic progression and disease activity in subjects with PsA treated with adalimumab (ADA) or placebo (PBO) and the impact of concomitant MTX. Methods This was a post hoc analysis of the randomized, double-blind, PBO-controlled ADEPT trial. Subjects were categorized according to time-averaged (TA) disease activity (remission, low, moderate or high) based on Disease Activity Score of 28 joints with CRP [DAS28(CRP)], Disease Activity Index for Psoriatic Arthritis (DAPSA) or Psoriatic Arthritis Disease Activity Score (PASDAS), and achievement of minimal disease activity (MDA) at week 24. Radiographic progression was assessed as change in modified total Sharp score (ΔmTSS) from baseline to week 24. The analyses included interaction terms between disease activity and treatment on radiographic progression, comparison of radiographic progression in subjects categorized by disease activity and treatment, and correlation between disease activity and radiographic progression by treatment. Results The interaction terms for TA disease activity and treatment on ΔmTSS were significant (P = 0.002–0.008). Irrespective of concomitant MTX, ΔmTSS was lower with ADA vs PBO in all disease activity categories. Importantly, even in subjects having moderate or high disease activity or not achieving MDA, ΔmTSS was significantly lower on ADA than PBO (P = 0.05–0.001 for TA-DAPSA, TA-PASDAS and MDA). Correlations between TA disease activity scores and ΔmTSS were moderately positive and significant (P < 0.001) with PBO but non-significant with ADA. Conclusion Among subjects with PsA treated with ADA, there was evidence of a ‘disconnect’ between disease activity and radiographic progression: inhibition of radiographic progression was greater than expected based on control of clinical disease activity alone. MTX had no added effect. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT00646386.
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Affiliation(s)
- Robert Landewé
- Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology & Immunology Centre, Amsterdam, The Netherlands
| | - Christopher T Ritchlin
- Allergy, Immunology & Rheumatology Division, University of Rochester Medical Center, Rochester, NY, USA
| | - Daniel Aletaha
- Division of Rheumatology, Department of Internal Medicine, Medical University of Vienna, Vienna, Austria
| | | | | | | | - Laura C Coates
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
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Mulder MLM, Vriezekolk JE, den Broeder N, Mahler EAM, Helliwell PS, van den Hoogen FHJ, den Broeder AA, Wenink MH. Comparing methotrexate monotherapy with methotrexate plus leflunomide combination therapy in psoriatic arthritis: protocol of a randomized, placebo-controlled, double-blind clinical trial (COMPLETE-PsA). Trials 2020; 21:155. [PMID: 32041657 PMCID: PMC7011519 DOI: 10.1186/s13063-020-4097-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 01/20/2020] [Indexed: 11/23/2022] Open
Abstract
Background Both methotrexate (MTX) and leflunomide (LEF) are registered and regularly prescribed as first-line treatments for the use in patients with psoriatic arthritis (PsA) and they are occasionally used in combination. However, evidence about their individual, and especially combined efficacy, in PsA is lacking. The aim of this study is to compare the effectiveness and safety of MTX and LEF combination therapy to MTX monotherapy in patients with PsA. Methods COMPLETE-PsA is a randomized, placebo-controlled, double-blind clinical trial. Disease-modifying antirheumatic drug (DMARD)-untreated patients (n = 78) with clinical diagnosis of active (i.e. ≥2 swollen joints) PsA will be randomized 1:1 (stratified for high disease activity, Psoriatic Arthritis Disease Activity Score [PASDAS] ≥ 5.4) to the combination or monotherapy. The intervention group receives MTX 25 mg (oral or subcutaneous) once weekly plus LEF 20 mg daily, and the control group receives the same but with placebo instead of LEF daily. Primary endpoint is between-group difference in PASDAS at 16 weeks, adjusted for baseline PASDAS. Key secondary parameters include between-group comparisons in change in Disease Activity in Psoriatic Arthritis (DAPSA) score, skin score, enthesitis score, dactylitis score, and swollen/tender joint count, as well as the proportion of patients fulfilling minimal disease activity (MDA), American College of Rheumatology (ACR) 20/50/70 response criteria at week 16. Furthermore, safety, function and quality of life (Health Assessment Questionnaire [HAQ], Psoriatic Arthritic Impact of Disease [PSAID], Short Form 12 [SF-12]) will be assessed. Discussion This is, to our knowledge, the first randomized, placebo-controlled, double-blind clinical trial assessing the effectiveness of MTX and LEF combination therapy in patients with PsA. The study will provide important information for treatment strategies and treatment recommendations. Trial registration Dutch Trial Register NTR7632 (3 December 2018). CMO NL66544.091.18 (19 November 2018).
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Affiliation(s)
- Michelle L M Mulder
- Department of Rheumatology, Sint Maartenskliniek, PO Box 9011, Nijmegen, 6500 GM, The Netherlands. .,Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
| | - Johanna E Vriezekolk
- Department of Rheumatology, Sint Maartenskliniek, PO Box 9011, Nijmegen, 6500 GM, The Netherlands
| | - Nathan den Broeder
- Department of Rheumatology, Sint Maartenskliniek, PO Box 9011, Nijmegen, 6500 GM, The Netherlands
| | - Elien A M Mahler
- Department of Rheumatology, Sint Maartenskliniek, PO Box 9011, Nijmegen, 6500 GM, The Netherlands
| | - Philip S Helliwell
- Leeds Institute of Rheumatology and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Frank H J van den Hoogen
- Department of Rheumatology, Sint Maartenskliniek, PO Box 9011, Nijmegen, 6500 GM, The Netherlands.,Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Alfons A den Broeder
- Department of Rheumatology, Sint Maartenskliniek, PO Box 9011, Nijmegen, 6500 GM, The Netherlands.,Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Mark H Wenink
- Department of Rheumatology, Sint Maartenskliniek, PO Box 9011, Nijmegen, 6500 GM, The Netherlands
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Treatment of Medicare Patients with Moderate-to-Severe Psoriasis who Cannot Afford Biologics or Apremilast. Am J Clin Dermatol 2020; 21:109-117. [PMID: 31452091 DOI: 10.1007/s40257-019-00468-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Elderly patients are a group with a high frequency of psoriasis. Their disease burden has negative impacts on their quality of life. While there is a clear need to treat these patients, there are challenges in doing so. This work seeks to define the challenges that exist in treating elderly Medicare patients, as well as to provide treatment suggestions for providers to follow if they encounter one or more of these challenges. Providers face the following challenges when creating treatment plants for elderly patients with psoriasis: difficulty in obtaining drug coverage through Medicare, increased medical comorbidities, and polypharmacy. Providers aim for regimens that are affordable, safe, and efficacious, but it is not always clear how to achieve this combination, especially in elderly Medicare patients. This work is relevant in that it aims to explain the logistical roadblocks posed by Medicare coverage and provide solutions for commonly encountered issues in the treatment of a disabling and common disease in a high-risk population. Specifically, alternative treatment options to biologics and small-molecule inhibitors are discussed and include topical therapies, phototherapy, methotrexate, acitretin, and cyclosporine and for psoriatic arthritis include corticosteroids and leflunomide. The specific risks and benefits of these therapies in the elderly population are provided, allowing providers to make patient-specific decisions about optimal regimens.
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Mease PJ, Liu C, Siegel E, Richmond H, Wu M, Chen L, Douglas K, Lockshin B. Impact of Clinical Specialty Setting and Geographic Regions on Disease Management in Patients with Psoriatic Arthritis in the United States: A Multicenter Observational Study. Am J Clin Dermatol 2019; 20:873-880. [PMID: 31612380 PMCID: PMC6872709 DOI: 10.1007/s40257-019-00470-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Background Information on the factors that influence treatment management decisions for psoriatic arthritis (PsA) is limited. Objective Our objective was to evaluate the impact of clinical specialty setting and geographic region on the management of patients with PsA in the USA. Methods LOOP was a multicenter, cross-sectional, observational study conducted across 44 sites in the USA. Patients were aged ≥ 18 years with a suspected or established diagnosis of PsA and were routinely visiting a rheumatologist or dermatologist. All patients enrolled in the study were assessed by both a rheumatologist and a dermatologist. Primary outcomes were the times from symptom onset to PsA diagnosis; PsA diagnosis to first conventional synthetic disease-modifying antirheumatic drug (csDMARD); PsA diagnosis to first biologic DMARD (bDMARD); and first csDMARD to first bDMARD. Results Of 681 patients enrolled in the study, 513 had a confirmed diagnosis of PsA and were included in this analysis. More patients were recruited by rheumatologists (71.3%) than by dermatologists (28.7%). The median time from symptom onset to diagnosis of PsA was significantly shorter for patients enrolled by rheumatologists than for those enrolled by dermatologists (1.0 vs. 2.6 years; p < 0.001). Disease activity and burden were generally similar across enrolling specialties. However, patients in western areas of the USA had less severe disease than those in central or eastern areas, including measures of joint involvement, enthesitis, and dactylitis. Conclusions There was a substantial delay in the time from symptom onset to diagnosis in this study population, and this was significantly longer for patients enrolled in the dermatology versus the rheumatology setting. This supports the need for collaboration across specialties to ensure faster recognition and treatment of PsA. Electronic supplementary material The online version of this article (10.1007/s40257-019-00470-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Phillip J Mease
- Swedish Medical Center, Providence St. Joseph Health, and University of Washington, Seattle, WA, USA.
| | - Clive Liu
- Bellevue Dermatology Clinic, Bellevue, WA, USA
| | - Evan Siegel
- Arthritis and Rheumatism Associates and Georgetown University, Rockville, MD, USA
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Khanna I, Kozicky O, Fischer H. Use of FDA-Approved Medications: Biologics for Psoriatic Arthritis in Patients at an Urban Outpatient Rheumatology Clinic. ACR Open Rheumatol 2019; 1:580-584. [PMID: 31777842 PMCID: PMC6857978 DOI: 10.1002/acr2.11077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 08/12/2019] [Indexed: 11/10/2022] Open
Abstract
Objective Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis that manifests as peripheral arthritis, dactylitis, enthesitis, and spondylitis. Biologics, particularly tumor necrosis factor inhibitors (TNFis) and some interleukin 17 (IL‐17) and interleukin 23 (IL‐23) inhibitors, are the only US Food and Drug Administration (FDA)–approved treatments shown to limit joint damage in clinical trials for PsA. Conventional synthetic disease‐modifying antirheumatic drugs have also been adapted to PsA treatment. Current 2018 American College of Rheumatology (ACR) guidelines regard TNFis as first‐line therapy in treatment‐naïve patients. The aim of this project is to review the prescribing practices for patients with PsA at an urban rheumatology office, with a focus on biologic prescribing. Methods A retrospective chart review was performed to search for patients seen from June 1, 2017, to June 1, 2018, using International Classification of Diseases, 10th Revision codes for PsA. A log of prescribing practices listed the use of biologics versus oral small molecules (OSMs) (methotrexate, sulfasalazine, leflunomide, and apremilast) across different ages, sex, and disease severity. Results This study included a total of 97 patients (40 women and 57 men), and 66% were on biologics (60% of women and 70% of men). There was no sex bias in biologic prescribing (P = 0.59). Use of biologics was highest in the 38 to 57 years age group and lowest in the 78 to 97 years age group, although, statistically, there was no age bias in biologic prescribing (P = 0.22). Biologics provided superior disease control (84.37%) compared with nonbiologics (66.6%) (P = 0.0016). OSMs provided slightly better control (69.5%) over apremilast monotherapy (61.5%) (P = 0.016). Conclusion There is no age or sex bias in prescribing practices for PsA. In accordance with the ACR, patients with controlled symptoms on OSMs are being appropriately maintained. Although apremilast is allocated as an add‐on therapy, 13.4% of patients were on apremilast monotherapy. This quality improvement project reveals that in most instances, biologics are being appropriately initiated as the primary mode of therapy for patients with PsA at our outpatient practice; however, treatment modifications can be made regarding patients who are managed with apremilast alone.
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Affiliation(s)
- Ira Khanna
- Medicine at Mount Sinai Beth Israel New York New York
| | | | - Harry Fischer
- Medicine at Mount Sinai Beth Israel New York New York
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Pakchotanon R, Ye JY, Cook RJ, Chandran V, Gladman DD. Liver Abnormalities in Patients with Psoriatic Arthritis. J Rheumatol 2019; 47:847-853. [PMID: 31615918 DOI: 10.3899/jrheum.181312] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2019] [Indexed: 12/17/2022]
Abstract
OBJECTIVE We aimed to determine the prevalence and incidence, and to identify the factors associated with liver abnormalities in patients with psoriatic arthritis (PsA). METHODS From a longitudinal cohort study, we identified PsA patients with either elevated serum transaminase or alkaline phosphatase levels or liver disease after the first visit to the PsA clinic (cases). Controls were subjects from the same cohort who never had such abnormalities or liver disease. Cases and controls were matched 1:1 by sex, age at the first clinic visit, and followup duration; variables at the onset of the first appearance of liver test abnormality associated with liver abnormalities were identified using univariate logistic and multivariate logistic regression analyses. RESULTS Among 1061 patients followed in the PsA clinic, 343 had liver abnormalities. Two hundred fifty-six patients who developed liver abnormalities after the first visit were identified as cases, and 718 patients were identified as controls. The prevalence of liver abnormalities was 32% and the incidence was 39/1000 patient-years where there were 256 cases over 6533 total person-years in the PsA cohort. Liver abnormalities were detected after a mean (SD) followup duration of 8.3 ± 7.8 years. The common causes of liver abnormalities were drug-induced hepatitis and fatty liver. Independent factors associated with liver abnormalities were higher body mass index (BMI), daily alcohol intake, higher damaged joint count, elevated C-reactive protein, and use of methotrexate, leflunomide, or tumor necrosis factor inhibitors. CONCLUSION Liver abnormalities are common among patients with PsA and are associated with higher BMI, more severe disease, and certain therapies.
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Affiliation(s)
- Rattapol Pakchotanon
- From the Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Toronto; Department of Statistics and Actuarial Science, University of Waterloo, Waterloo; University of Toronto, Department of Medicine, Division of Rheumatology, University of Toronto, Toronto; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutlao Hospital and College of Medicine, Bangkok, Thailand.,R. Pakchotanon, MD, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, and Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutlao Hospital and College of Medicine; J.Y. Ye, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; R.J. Cook, PhD, Professor, Department of Statistics and Actuarial Science, University of Waterloo; V. Chandran, MBBS, MD, DM, PhD, Assistant Professor, University of Toronto, Department of Medicine, Division of Rheumatology, University of Toronto, Co-Director, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; D.D. Gladman, MD, FRCPC, Director, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Senior Scientist, Krembil Research Institute, Toronto Western Hospital, University Health Network
| | - Justine Yang Ye
- From the Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Toronto; Department of Statistics and Actuarial Science, University of Waterloo, Waterloo; University of Toronto, Department of Medicine, Division of Rheumatology, University of Toronto, Toronto; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutlao Hospital and College of Medicine, Bangkok, Thailand.,R. Pakchotanon, MD, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, and Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutlao Hospital and College of Medicine; J.Y. Ye, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; R.J. Cook, PhD, Professor, Department of Statistics and Actuarial Science, University of Waterloo; V. Chandran, MBBS, MD, DM, PhD, Assistant Professor, University of Toronto, Department of Medicine, Division of Rheumatology, University of Toronto, Co-Director, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; D.D. Gladman, MD, FRCPC, Director, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Senior Scientist, Krembil Research Institute, Toronto Western Hospital, University Health Network
| | - Richard J Cook
- From the Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Toronto; Department of Statistics and Actuarial Science, University of Waterloo, Waterloo; University of Toronto, Department of Medicine, Division of Rheumatology, University of Toronto, Toronto; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutlao Hospital and College of Medicine, Bangkok, Thailand.,R. Pakchotanon, MD, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, and Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutlao Hospital and College of Medicine; J.Y. Ye, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; R.J. Cook, PhD, Professor, Department of Statistics and Actuarial Science, University of Waterloo; V. Chandran, MBBS, MD, DM, PhD, Assistant Professor, University of Toronto, Department of Medicine, Division of Rheumatology, University of Toronto, Co-Director, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; D.D. Gladman, MD, FRCPC, Director, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Senior Scientist, Krembil Research Institute, Toronto Western Hospital, University Health Network
| | - Vinod Chandran
- From the Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Toronto; Department of Statistics and Actuarial Science, University of Waterloo, Waterloo; University of Toronto, Department of Medicine, Division of Rheumatology, University of Toronto, Toronto; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutlao Hospital and College of Medicine, Bangkok, Thailand.,R. Pakchotanon, MD, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, and Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutlao Hospital and College of Medicine; J.Y. Ye, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; R.J. Cook, PhD, Professor, Department of Statistics and Actuarial Science, University of Waterloo; V. Chandran, MBBS, MD, DM, PhD, Assistant Professor, University of Toronto, Department of Medicine, Division of Rheumatology, University of Toronto, Co-Director, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; D.D. Gladman, MD, FRCPC, Director, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Senior Scientist, Krembil Research Institute, Toronto Western Hospital, University Health Network
| | - Dafna D Gladman
- From the Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Toronto; Department of Statistics and Actuarial Science, University of Waterloo, Waterloo; University of Toronto, Department of Medicine, Division of Rheumatology, University of Toronto, Toronto; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutlao Hospital and College of Medicine, Bangkok, Thailand. .,R. Pakchotanon, MD, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, and Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutlao Hospital and College of Medicine; J.Y. Ye, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; R.J. Cook, PhD, Professor, Department of Statistics and Actuarial Science, University of Waterloo; V. Chandran, MBBS, MD, DM, PhD, Assistant Professor, University of Toronto, Department of Medicine, Division of Rheumatology, University of Toronto, Co-Director, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; D.D. Gladman, MD, FRCPC, Director, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Senior Scientist, Krembil Research Institute, Toronto Western Hospital, University Health Network.
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Abstract
Psoriatic arthritis (PsA) is a very heterogeneous immune-mediated disease that usually involves skin and joints but can also affect entheses and extra-articular structures during the disease course. Furthermore, it can also be linked with other associated diseases. Therefore, the individualized selection of an effective and patient-oriented treatment must be carried out taking the extent of various manifestations of the PsA itself and also of other influencing factors into consideration. Various recommendations for selection and control of the suitable treatment of PsA are available for clinical use. The recommendations of the European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) are the two recommendations that are frequently used and internationally acknowledged. Both recommendations were updated in 2016. Specific German treatment recommendations are currently missing. In analogy to the treat-to-target strategy for rheumatoid arthritis, at least minimal disease activity (MDA) should be achieved in PsA patients with the use of specific therapeutic interventions if remission as the maximum therapeutic goal cannot be reached. New treatment options, which target different specific molecules, offer possibilities for a more differentiated personalized medicinal treatment for improvement of the care of PsA patients. This particularly applies to a focus on personalized strategies for optimal treatment of various manifestation forms and patterns.
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Affiliation(s)
- M Köhm
- Abteilung Rheumatologie, Goethe-Universität Frankfurt/Main, Theodor-Stern-Kai 7, 60596, Frankfurt/Main, Deutschland
- Institutsteil Translationale Medizin und Pharmakologie (TMP), Fraunhofer IME, Frankfurt/Main, Deutschland
| | - F Behrens
- Abteilung Rheumatologie, Goethe-Universität Frankfurt/Main, Theodor-Stern-Kai 7, 60596, Frankfurt/Main, Deutschland.
- Institutsteil Translationale Medizin und Pharmakologie (TMP), Fraunhofer IME, Frankfurt/Main, Deutschland.
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Behrens F, Koehm M, Schwaneck EC, Schmalzing M, Wittig BM, Gnann H, Greger G, Tony HP, Burkhardt H. Addition or removal of concomitant methotrexate alters adalimumab effectiveness in rheumatoid arthritis but not psoriatic arthritis. Scand J Rheumatol 2019; 48:375-382. [DOI: 10.1080/03009742.2019.1600717] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- F Behrens
- Division of Rheumatology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology TMP, Frankfurt am Main, Germany
| | - M Koehm
- Division of Rheumatology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology TMP, Frankfurt am Main, Germany
| | - EC Schwaneck
- Medizinische Klinik und Poliklinik 2, Department of Rheumatology and Clinical Immunology, University Hospital Würzburg, Würzburg, Germany
| | - M Schmalzing
- Medizinische Klinik und Poliklinik 2, Department of Rheumatology and Clinical Immunology, University Hospital Würzburg, Würzburg, Germany
| | - BM Wittig
- AbbVie Germany GmbH & Co. KG, Wiesbaden, Germany
| | - H Gnann
- Department of Biostatistics, GKM, Munich, Germany
| | - G Greger
- AbbVie Germany GmbH & Co. KG, Wiesbaden, Germany
| | - H-P Tony
- Medizinische Klinik und Poliklinik 2, Department of Rheumatology and Clinical Immunology, University Hospital Würzburg, Würzburg, Germany
| | - H Burkhardt
- Division of Rheumatology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology TMP, Frankfurt am Main, Germany
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48
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FitzGerald O, Ritchlin C. Opportunities and challenges in the treatment of psoriatic arthritis. Best Pract Res Clin Rheumatol 2019; 32:440-452. [PMID: 31171314 DOI: 10.1016/j.berh.2019.03.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
In this chapter, we review the opportunities and challenges posed by the treatment options currently available in the treatment of psoriatic arthritis. Both established and new or emerging treatment options are discussed using a domain-based approach. Finally, approaches to how treatment can be optimized together with some clinical pearls are presented and discussed. With the increasing treatment options available, we need a better way of deciding which treatment should be considered for which patient. On the basis of current knowledge, some guidance is provided on how these choices might best be made.
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Affiliation(s)
- Oliver FitzGerald
- St. Vincent's University Hospital, Conway Institute for Biomolecular Research, University College Dublin, Ireland.
| | - Christopher Ritchlin
- Chief, Allergy, Immunology & Rheumatology Division, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA
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49
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Abstract
Peripheral spondyloarthritis refers to spondyloarthritis with predominant peripheral (arthritis, enthesitis or dactylitis) involvement. Diagnosis can be challenging, particularly in the absence of SpA extra-articular manifestations such as uveitis, psoriasis or inflammatory bowel disease. Evaluation of disease activity should always include assessment of objective signs of inflammation, particularly in the presence of enthesitis as the sole peripheral manifestation, mainly due to the potential misdiagnosis with fibromyalgia tender points. Several recommendations for management/treatment of psoriatic arthritis have been published by EULAR and GRAPPA but none for peripheral SpA in general. NSAIDs and glucocorticoids are recommended as the first step of treatment in all peripheral manifestations, while conventional synthetic (cs) DMARDs seem only efficacious in arthritis. Several biologics and targeted synthetic (ts) DMARDs (TNFi, anti-IL17 and JAK-inhibitors) have been proven to be efficacious in peripheral involvement in PsA (arthritis and enthesitis), but studies on peripheral SpA are lacking.
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Affiliation(s)
- Anna Molto
- Rheumatology Department, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; INSERM (U-1153), CRESS, Paris, France.
| | - Joachim Sieper
- Rheumatology, Charité, Campus Benjamin Franklin, Berlin, 12200, Germany
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50
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Abstract
Methotrexate (MTX) is widely used in the treatment of psoriatic arthritis (PsA), despite the evidence base for this being limited. This narrative review summarizes the evidence to date of using MTX within different domains of psoriatic disease, including peripheral arthritis, axial disease, dactylitis, enthesitis, psoriasis, and nail disease. We also explore the role of MTX in combination therapy with tumor necrosis factor inhibitors, in addition to its safety and tolerability, to answer the question: should methotrexate have any place in the treatment of psoriatic arthritis?
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