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Lopalco G, Cito A, Venerito V, Iannone F, Proft F. The management of axial spondyloarthritis with cutting-edge therapies: advancements and innovations. Expert Opin Biol Ther 2024; 24:835-853. [PMID: 39109494 DOI: 10.1080/14712598.2024.2389987] [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: 05/28/2024] [Accepted: 08/05/2024] [Indexed: 08/28/2024]
Abstract
INTRODUCTION Axial involvement in spondyloarthritis has significantly evolved from the original 1984 New York criteria for ankylosing spondylitis, leading to an improved understanding of axial spondyloarthritis (axSpA) as a disease continuum encompassing non- radiographic axSpA (nr-axSpA) and radiographic axSpA (r-axSpA). A clear definition for early axSpA has been established, underscoring the need for early intervention with biological and targeted synthetic drugs to mitigate pain, reduce functional impairment, and prevent radiographic progression. AREAS COVERED This review explores therapeutic strategies in axSpA management, focusing on biological and targeted synthetic therapies and recent advancements. Biologics targeting TNFα or IL-17 and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) are primary treatment options. These therapies significantly impact clinical outcomes, radiographic progression, and patient-reported functional improvement. EXPERT OPINION AxSpA treatment has evolved significantly, offering various therapeutic options. Biological DMARDs, particularly TNFα inhibitors, have transformed treatment, significantly enhancing patient outcomes. However, challenges persist for patients unresponsive or intolerant to existing therapies. Emerging therapeutic targets promise to address these challenges. Comprehensive management strategies and personalized approaches, considering extra-articular manifestations and individual patient factors, are crucial for achieving optimal outcomes in axSpA management.
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Affiliation(s)
- Giuseppe Lopalco
- Department of Precision Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Bari, Italy
| | - Andrea Cito
- Department of Precision Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Bari, Italy
| | - Vincenzo Venerito
- Department of Precision Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Bari, Italy
| | - Florenzo Iannone
- Department of Precision Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Bari, Italy
| | - Fabian Proft
- Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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Maatallah K, Cherif I, Ferjani H, Ben Nessib D, Boumaiza R, Kaffel D, Hamdi W. Navigating the Factors Affecting Functional Impairment in Spondyloarthritis. Sultan Qaboos Univ Med J 2024; 24:235-242. [PMID: 38828242 PMCID: PMC11139368 DOI: 10.18295/squmj.3.2024.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 01/07/2024] [Accepted: 01/23/2024] [Indexed: 06/05/2024] Open
Abstract
Objectives This study aimed to assess the predictive factors of functional impairment in spondyloarthritis (SpA) patients assessed with bath ankylosing spondylitis functional index (BASFI) and Lequesne Index (LI). Methods This retrospective study was conducted at the Rheumatology Department of Mohamed Kassab Institute of Orthopedics, Manubah, Tunisia, and collected data from 2008 to 2019 over a period of 4 months (August to November 2019). Socio-demographic and disease-related data of SpA patients were collected. Disease activity was assessed using the bath ankylosing spondylitis-global score (BASG-s) and the bath ankylosing spondylitis disease activity index (BASDAI). The spinal mobility was evaluated by the bath ankylosing spondylitis metrology index (BASMI). Structural progression was evaluated with the bath ankylosing spondylitis radiologic index (BASRI) and modified stoke ankylosing spondylitis spine score (mSASSS). A multivariate analysis was done to search for predictive factors associated with BASFI and LI. Results A total of 263 patients were included. The mean age was 38.9 ± 12.7 years and the gender ratio was 2.7. The mean age of onset of SpA was 27.6 ± 10.8 years and disease duration was 11.3 ± 9.5 years. Occupation was significantly associated with BASFI and LI scores. A significant functional impact was notably correlated with a long duration of the disease. The two scores were correlated with a limitation of spinal mobility (BASMI), a greater disease activity (BASDAI and erythrocyte sedimentation rate) and a greater impact of the disease on health status (BASG-s). Significant functional impairment was also correlated with structural impairment (mSASSS, BASRI and sacroiliitis grade). The variables independently related to BASFI were the mSASSS score and the BASDAI. The variables independently related to LI were profession (unemployed subjects had higher scores), the mSASSS score and the BASMI. Conclusion Occupation, disease activity, mobility and structural progression predicted functional impairment in Tunisian SpA patients.
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Affiliation(s)
- Kaouther Maatallah
- University Tunis El Manar, Faculty of Medicine, Tunis, Tunisia; Kassab Institute of Orthopedics, Manubah, Tunisia
| | - Ines Cherif
- University Tunis El Manar, Faculty of Medicine, Tunis, Tunisia; Kassab Institute of Orthopedics, Manubah, Tunisia
| | - Hanen Ferjani
- University Tunis El Manar, Faculty of Medicine, Tunis, Tunisia; Kassab Institute of Orthopedics, Manubah, Tunisia
| | - Dorra Ben Nessib
- University Tunis El Manar, Faculty of Medicine, Tunis, Tunisia; Kassab Institute of Orthopedics, Manubah, Tunisia
| | - Rania Boumaiza
- University Tunis El Manar, Faculty of Medicine, Tunis, Tunisia; Kassab Institute of Orthopedics, Manubah, Tunisia
| | - Dhia Kaffel
- University Tunis El Manar, Faculty of Medicine, Tunis, Tunisia; Kassab Institute of Orthopedics, Manubah, Tunisia
| | - Wafa Hamdi
- University Tunis El Manar, Faculty of Medicine, Tunis, Tunisia; Kassab Institute of Orthopedics, Manubah, Tunisia
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Bautista-Molano W, Fernández-Ávila DG, Brance ML, Ávila Pedretti MG, Burgos-Vargas R, Corbacho I, Cosentino VL, Díaz Coto JF, Giraldo Ho E, Gomes Resende G, Gutiérrez LA, Gutiérrez M, Ibáñez Vodnizza SE, Jáuregui E, Ocampo V, Palleiro Rivero DR, Palominos PE, Pacheco Tena C, Quiceno GA, Saldarriaga-Rivera LM, Sommerfleck FA, Goecke Sariego A, Vera Barrezueta C, Vega Espinoza LE, Vega Hinojosa O, Citera G, Lozada C, Sampaio-Barros PD, Schneeberger E, Soriano ER. Pan American League of Associations for Rheumatology recommendations for the management of axial spondyloarthritis. Nat Rev Rheumatol 2023; 19:724-737. [PMID: 37803079 DOI: 10.1038/s41584-023-01034-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2023] [Indexed: 10/08/2023]
Abstract
Axial spondyloarthritis (axSpA) comprises a spectrum of chronic inflammatory manifestations affecting the axial skeleton and represents a challenge for diagnosis and treatment. Our objective was to generate a set of evidence-based recommendations for the management of axSpA for physicians, health professionals, rheumatologists and policy decision makers in Pan American League of Associations for Rheumatology (PANLAR) countries. Grading of Recommendations, Assessment, Development and Evaluation-ADOLOPMENT methodology was used to adapt existing recommendations after performing an independent systematic search and synthesis of the literature to update the evidence. A working group consisting of rheumatologists, epidemiologists and patient representatives from countries within the Americas prioritized 13 topics relevant to the context of these countries for the management of axSpA. This Evidence-Based Guideline article reports 13 recommendations addressing therapeutic targets, the use of NSAIDs and glucocorticoids, treatment with DMARDs (including conventional synthetic, biologic and targeted synthetic DMARDs), therapeutic failure, optimization of the use of biologic DMARDs, the use of drugs for extra-musculoskeletal manifestations of axSpA, non-pharmacological interventions and the follow-up of patients with axSpA.
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Affiliation(s)
- Wilson Bautista-Molano
- Hospital Universitario Fundación Santafé de Bogotá, Faculty of Medicine, Universidad El Bosque, Universidad Militar Nueva Granada, Bogotá, Colombia
| | | | - María Lorena Brance
- Bone Biology Laboratory, School of Medicine, Rosario National University, Rosario, Argentina
| | | | | | - Inés Corbacho
- Cátedra de Reumatologia, Universidad de la República UDELAR, Montevideo, Uruguay
| | | | | | | | | | | | - Marwin Gutiérrez
- Center of Excellence of Rheumatic and Musculoskeletal Diseases, C.E.R.M, Mexico City, Mexico
| | | | - Edwin Jáuregui
- Gestor de Reumatología de o en Riesgo de fractura S.A, Bogotá, Colombia
| | - Vanessa Ocampo
- Rheumatology, University of Toronto, Toronto, ON, Canada
| | | | | | - Cesar Pacheco Tena
- Facultad de Medicina, Universidad Autónoma de Chihuahua e Investigación y Biomedicina de Chihuahua SC, Chihuahua, Mexico
| | - Guillermo Andrés Quiceno
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Lina María Saldarriaga-Rivera
- Faculty of Medicine, Universidad Tecnológica de Pereira, Hospital Universitario San Jorge de Pereira, Pereira, Risaralda, Colombia
| | | | | | | | | | - Oscar Vega Hinojosa
- Centro Médico Reumacenter y Hospital III Red Asistencial Essalud, Juliaca, Perú
| | - Gustavo Citera
- Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina
| | - Carlos Lozada
- Division of Rheumatology, University of Miami Miller School of Medicine, Miami, FL, USA
| | | | | | - Enrique R Soriano
- Rheumatology Unit, Internal Medicine Services and University Institute, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
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Seo MR, Yeo J, Park JW, Lee YA, Lee JH, Kang EH, Ji SM, Kwon SR, Kim SK, Kim TJ, Kim TH, Kim HW, Park MC, Shin K, Lee SH, Lee EY, Cha HS, Shim SC, Yoon Y, Lee SH, Lim JH, Baek HJ. Korean treatment recommendations for patients with axial spondyloarthritis. Korean J Intern Med 2023; 38:620-640. [PMID: 37482652 PMCID: PMC10493447 DOI: 10.3904/kjim.2023.194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/13/2023] [Accepted: 06/16/2023] [Indexed: 07/25/2023] Open
Abstract
We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5-12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13-16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.
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Affiliation(s)
- Mi Ryoung Seo
- Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon,
Korea
| | - Jina Yeo
- Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon,
Korea
| | - Jun Won Park
- Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
| | - Yeon-Ah Lee
- Division of Rheumatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul,
Korea
| | - Ju Ho Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
Korea
| | - Eun Ha Kang
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
Korea
| | - Seon Mi Ji
- National Health Insurance Service, Wonju,
Korea
| | - Seong-Ryul Kwon
- Division of Rheumatology, Department of Internal Medicine, Inha University College of Medicine. Incheon,
Korea
| | - Seong-Kyu Kim
- Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu,
Korea
| | - Tae-Jong Kim
- Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju,
Korea
| | - Tae-Hwan Kim
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul,
Korea
| | - Hye Won Kim
- Division of General Internal Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
Korea
| | - Min-Chan Park
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea
| | - Kichul Shin
- Division of Rheumatology, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul,
Korea
| | - Sang-Hoon Lee
- Department of Rheumatology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul,
Korea
| | - Eun Young Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
| | - Hoon Suk Cha
- Division of Rheumatology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Seung Cheol Shim
- Division of Rheumatology, Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital. Daejeon,
Korea
| | - Youngim Yoon
- Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
| | - Seung Ho Lee
- Korea Ankylosing Spondylitis Society, Seoul,
Korea
| | - Jun Hong Lim
- Korea Ankylosing Spondylitis Corporation, Daejeon,
Korea
| | - Han Joo Baek
- Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon,
Korea
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Cassinotti A, Batticciotto A, Parravicini M, Lombardo M, Radice P, Cortelezzi CC, Segato S, Zanzi F, Cappelli A, Segato S. Evidence-based efficacy of methotrexate in adult Crohn's disease in different intestinal and extraintestinal indications. Therap Adv Gastroenterol 2022; 15:17562848221085889. [PMID: 35340755 PMCID: PMC8949794 DOI: 10.1177/17562848221085889] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 02/18/2022] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION Methotrexate (MTX) is included in the therapeutic armamentarium of Crohn's disease (CD), although its positioning is currently uncertain in an era in which many effective biological drugs are available. No systematic reviews or meta-analysis have stratified the clinical outcomes of MTX according to the specific clinical scenarios of its use. METHODS Medline, PubMed and Scopus were used to extract eligible studies, from database inception to May 2021. A total of 163 studies were included. A systematic review was performed by stratifying the outcomes of MTX according to formulation, clinical indication and criteria of efficacy. RESULTS The use of MTX is supported by randomized clinical trials only in steroid-dependent CD, with similar outcomes to thiopurines. The use of MTX in patients with steroid-refractoriness, failure of thiopurines or in combination with biologics is not supported by high levels of evidence. Combination therapy with biologics can optimize the immunogenic profile of the biological drug, but the impact on long-term clinical outcomes is described only in small series with anti-TNFα. Other off-label uses, such as fistulizing disease, mucosal healing, postoperative prevention and extraintestinal manifestations, are described in small uncontrolled series. The best performance in most indications was shown by parenteral MTX, favouring higher doses (25 mg/week) in the induction phase. DISCUSSION Evidence from high-quality studies in favour of MTX is scarce and limited to the steroid-dependent disease, in which other drugs are the leading players today. Many limitations on study design have been found, such as the prevalence of retrospective underpowered studies and the lack of stratification of outcomes according to specific types of patients and formulations of MTX. CONCLUSION MTX is a valid option as steroid-sparing agent in steroid-dependent CD. Numerous other clinical scenarios require well-designed clinical studies in terms of patient profile, drug formulation and dosage, and criteria of efficacy.
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Affiliation(s)
| | | | | | | | - Paolo Radice
- Ophtalmology Unit, ASST Sette Laghi, Varese, Italy
| | | | - Simone Segato
- Gastroenterology Unit, ASST Sette Laghi, Varese, Italy
| | | | | | - Sergio Segato
- Gastroenterology Unit, ASST Sette Laghi, Varese, Italy
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Tack M. Problems with the MetaBLIND study: An examination of data on blinding patients in trials with patient-reported outcomes. J Health Psychol 2021:13591053211059391. [PMID: 34875934 DOI: 10.1177/13591053211059391] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
MetaBLIND is the largest meta-epidemiological study on the impact of blinding in randomized trials to date. We examined MetaBLIND data on the impact of blinding patients on patient-reported outcomes. 68 out of 132 included trials tested knowledge recall and had questionable relevance to clinical trials. In 17 out of 18 comparisons, the number of trials in the blinded or nonblinded group was 2 or lower. In several key trials, the blinding status was uncertain. Effect sizes compared in MetaBLIND appear to reflect random differences in study design and setting rather than the impact of blinding trial participants.
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Ebrahimiadib N, Berijani S, Ghahari M, Pahlaviani FG. Ankylosing Spondylitis. J Ophthalmic Vis Res 2021; 16:462-469. [PMID: 34394873 PMCID: PMC8358754 DOI: 10.18502/jovr.v16i3.9440] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 11/21/2020] [Indexed: 01/06/2023] Open
Abstract
The seronegative spondyloarthropathies are a group of autoimmune inflammatory diseases lacking rheumatoid factor or antinuclear antibody in their serum. They include ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, spondylitis associated with Crohn's disease and ulcerative colitis, and undifferentiated spondyloarthropathies. Inflammation mostly affects the axial joints, entheses, and extra-articular structures such as uveal tract, gastrointestinal tract, mucocutaneous tissue, and heart. Uveitis is the most common extra-articular manifestation. Spondyloarthropathies, especially AS, have a strong association with the presence of Human Leukocyte Antigen (HLA)-B27 gene. AS happens earlier in HLA-B27 patients and men are more prone to the disease. Uveitis, typically unilateral non-granulomatous acute anterior uveitis, occurs in up to 50% of the patients with AS. HLA-B27 positivity correlates with more frequent flare-ups. Conjunctivitis and scleritis are rare ocular manifestations of AS. To establish the diagnosis of AS, at least one clinical and one radiologic parameter are required for definitive diagnosis. Magnetic resonance imaging (MRI) or bone scan can help early detection of the axial skeleton inflammation. The course of eye and joint involvement are not correlated. Short-term treatment with topical corticosteroids and cycloplegic agents control the uveitis attack. In resistant cases, local or systemic therapy with corticosteroids are recommended. NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), methotrexate, azathioprine, anti-IL-17A monoclonal antibodies, and TNF-α antagonists are effective treatments for ocular and systemic manifestations of AS. If not treated adequately, uveitis may become recalcitrant and extend posteriorly. Functional impairment due to joint destruction can also occur as a result of under-treatment.
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Affiliation(s)
- Nazanin Ebrahimiadib
- Retina Service, Ocular Immunology and Uveitis Foundation, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Retina Service, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Sahar Berijani
- Retina Service, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Ghahari
- Retina Service, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
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McGonagle D, Aydin SZ, Marzo-Ortega H, Eder L, Ciurtin C. Hidden in plain sight: Is there a crucial role for enthesitis assessment in the treatment and monitoring of axial spondyloarthritis? Semin Arthritis Rheum 2021; 51:1147-1161. [PMID: 34537464 DOI: 10.1016/j.semarthrit.2021.07.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 07/05/2021] [Indexed: 01/06/2023]
Abstract
OBJECTIVE To review the evidence surrounding the pathophysiology of enthesitis in axial spondyloarthritis (axSpA), its prevalence and contribution to the overall disease burden, and response to treatment at axial and peripheral sites. METHODS Literature searches of the Cochrane Library, PubMed, and Embase / Medline using the terms "enthesitis", "enthesopathy", "spondyloarthritis", "axial spondyloarthritis", and "ankylosing spondylitis" were conducted. Publications mentioning enthesitis or enthesopathy in the context of pathophysiology, diagnosis, or treatment were included. RESULTS Enthesitis is a common symptom of axSpA, occurring with high prevalence at axial and several peripheral sites. Inflammation at the site of enthesis is an early key manifestation of axSpA. Clinically evaluable enthesitis contributes significantly to the burden of disease, correlating with worse symptomatology and downstream structural damage. Despite its importance in driving axSpA disease processes, enthesitis is somewhat neglected in current approaches to disease assessment and management. Enthesitis is excluded from some commonly used disease activity measures, is not routinely assessed in clinical practice, and many methods of clinical assessment omit key accessible axial sites, such as the spinous processes. CONCLUSION Enthesitis plays a central role in driving the pathophysiology of axSpA. There is a need for a renewed focus on the early detection, measurement and treatment of enthesitis.
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Affiliation(s)
- Dennis McGonagle
- The Leeds Institute of the Rheumatic and Musculoskeletal Disease, University of Leeds, Chapeltown Road, Leeds LS7 4SA, United Kingdom; National Institute for Health Research, Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds, United Kingdom.
| | - Sibel Z Aydin
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Ottawa, and Ottawa Hospital Research Institute, Ottawa, Canada
| | - Helena Marzo-Ortega
- The Leeds Institute of the Rheumatic and Musculoskeletal Disease, University of Leeds, Chapeltown Road, Leeds LS7 4SA, United Kingdom; National Institute for Health Research, Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds, United Kingdom
| | - Lihi Eder
- Division of Rheumatology, Department of Medicine, Women's College Research Institute, Women's College Hospital, University of Toronto, Canada
| | - Coziana Ciurtin
- Department of Rheumatology, Centre for Adolescent Rheumatology Versus Arthritis, Department of Medicine, University College London, Rayne Building, London, United Kingdom
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9
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Andreasen RA, Kristensen LE, Baraliakos X, Strand V, Mease PJ, de Wit M, Ellingsen T, Hansen IMJ, Kirkham J, Wells GA, Tugwell P, Maxwell L, Boers M, Egstrup K, Christensen R. Assessing the effect of interventions for axial spondyloarthritis according to the endorsed ASAS/OMERACT core outcome set: a meta-research study of trials included in Cochrane reviews. Arthritis Res Ther 2020; 22:177. [PMID: 32711571 PMCID: PMC7382035 DOI: 10.1186/s13075-020-02262-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 07/06/2020] [Indexed: 12/24/2022] Open
Abstract
The Assessment of SpondyloArthritis international Society (ASAS) has defined core sets for (i) symptom-modifying anti-rheumatic drugs (SM-ARD), (ii) clinical record keeping, and (iii) disease-controlling anti-rheumatic therapy (DC-ART). These include the following domains for all three core sets: “physical function,” “pain,” “spinal mobility,” “spinal stiffness,” and “patient’s global assessment” (PGA). The core set for clinical record keeping further includes the domains “peripheral joints/entheses” and “acute phase reactants,” and the core set for DC-ART further includes the domains “fatigue” and “spine radiographs/hip radiographs.” The Outcome Measures in Rheumatology (OMERACT) endorsed the core sets in 1998. Using empirical evidence from axSpA trials, we investigated the efficacy (i.e., net benefit) according to the ASAS/OMERACT core outcome set for axSpA across all interventions tested in trials included in subsequent Cochrane reviews. For all continuous scales, we combined data using the standardized mean difference (SMD) to meta-analyze outcomes involving the same domains. Also, through meta-regression analysis, we examined the effect of the separate SMD measures (independent variables) on the primary endpoint (log [OR], dependent variable) across all trials. Based on 11 eligible Cochrane reviews, from these, 85 articles were screened; we included 43 trials with 63 randomized comparisons. Mean (SD) number of ASAS/OMERACT core outcome domains measured for SM-ARD/physical therapy trials was 4.2 (1.7). Six trials assessed all proposed domains. Mean (SD) for number of core outcome domains for DC-ART trials was 5.8 (1.7). No trials assessed all nine domains. Eight trials (16%) were judged to have inadequate (i.e., high risk of) selective outcome reporting bias. The most responsible core domains for achieving success in meeting the primary objective per trial were pain, OR (95% CI) 5.19 (2.28, 11.77), and PGA, OR (95% CI) 1.87 (1.14, 3.07). In conclusion, selective outcome reporting (and “missing data”) should be reduced by encouraging the use of the endorsed ASAS/OMERACT outcome domains in clinical trials. Overall outcome reporting was good for SM-ARD/physical therapy trials and poor for DC-ART trials. Our findings suggest that both PGA and pain provide a valuable holistic construct for the assessment of improvement beyond more objective measures of spinal inflammation.
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Affiliation(s)
- Rikke A Andreasen
- Department of Medicine, Section of Rheumatology, Odense University Hospital, Svendborg and University of Southern Denmark, Odense, Denmark.,Musculoskeletal Statistics Unit, the Parker Institute, Bispebjerg and Frederiksberg Hospital, University Hospital, Copenhagen F, Denmark
| | - Lars E Kristensen
- Musculoskeletal Statistics Unit, the Parker Institute, Bispebjerg and Frederiksberg Hospital, University Hospital, Copenhagen F, Denmark
| | | | - Vibeke Strand
- Division Immunology/Rheumatology, Stanford University, Palo Alto, CA, USA
| | - Philip J Mease
- Swedish Medical Centre/Providence St. Joseph Health and University of Washington, Seattle, USA
| | | | - Torkell Ellingsen
- Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark
| | - Inger Marie J Hansen
- Department of Medicine, Section of Rheumatology, Odense University Hospital, Svendborg and University of Southern Denmark, Odense, Denmark
| | - Jamie Kirkham
- Centre for Biostatistics, Manchester Academic Health Science, Manchester, UK
| | - George A Wells
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Peter Tugwell
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Lara Maxwell
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Maarten Boers
- Department of Epidemiology & Biostatistics, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, the Netherlands
| | - Kenneth Egstrup
- Cardiovascular Research Unit, Odense University Hospital, Svendborg, Denmark
| | - Robin Christensen
- Musculoskeletal Statistics Unit, the Parker Institute, Bispebjerg and Frederiksberg Hospital, University Hospital, Copenhagen F, Denmark. .,Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.
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Resende GG, Meirelles EDS, Marques CDL, Chiereghin A, Lyrio AM, Ximenes AC, Saad CG, Gonçalves CR, Kohem CL, Schainberg CG, Campanholo CB, Bueno Filho JSDS, Pieruccetti LB, Keiserman MW, Yazbek MA, Palominos PE, Goncalves RSG, Lage RDC, Assad RL, Bonfiglioli R, Anti SMA, Carneiro S, Oliveira TL, Azevedo VF, Bianchi WA, Bernardo WM, Pinheiro MDM, Sampaio-Barros PD. The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis - 2019. Adv Rheumatol 2020; 60:19. [PMID: 32171329 DOI: 10.1186/s42358-020-0116-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Accepted: 01/22/2020] [Indexed: 12/13/2022] Open
Abstract
Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013.A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed.These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.
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Affiliation(s)
- Gustavo Gomes Resende
- Universidade Federal de Minas Gerais (UFMG), Alameda Álvaro Celso, 175 / 2° Andar. Santa Efigênia. CEP 30.150-260, Belo Horizonte, MG, Brazil.
| | | | | | | | - Andre Marun Lyrio
- Pontifície Universidade Católica (PUC) de Campinas, Campinas, Brazil
| | | | | | | | | | | | | | | | | | | | | | | | | | - Ricardo da Cruz Lage
- Universidade Federal de Minas Gerais (UFMG), Alameda Álvaro Celso, 175 / 2° Andar. Santa Efigênia. CEP 30.150-260, Belo Horizonte, MG, Brazil
| | | | | | | | - Sueli Carneiro
- Universidade Federal do Rio De Janeiro (UFRJ), Rio de Janeiro, Brazil
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Poddubnyy D, Amital H, Rubbert-Roth A. Should we combine biologics with methotrexate in axial spondyloarthritis? Autoimmun Rev 2019; 18:102402. [PMID: 31669544 DOI: 10.1016/j.autrev.2019.102402] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 06/30/2019] [Indexed: 01/06/2023]
Affiliation(s)
- Denis Poddubnyy
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Epidemiology, German Rheumatism Research Centre, Berlin, Germany
| | - Howard Amital
- Department of Medicine 'B', Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
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12
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Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, Haroon N, Borenstein D, Wang R, Biehl A, Fang MA, Louie G, Majithia V, Ng B, Bigham R, Pianin M, Shah AA, Sullivan N, Turgunbaev M, Oristaglio J, Turner A, Maksymowych WP, Caplan L. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Care Res (Hoboken) 2019; 71:1285-1299. [PMID: 31436026 PMCID: PMC6764857 DOI: 10.1002/acr.24025] [Citation(s) in RCA: 201] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 07/09/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. RESULTS Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. CONCLUSION These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.
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Affiliation(s)
- Michael M. Ward
- National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, Bethesda, Maryland
| | - Atul Deodhar
- Oregon Health & Science University, Portland, Oregon
| | | | | | - David Yu
- University of California, Los Angeles, Los Angeles, California
| | | | - Nigil Haroon
- Department of Medicine, University of Toronto, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada
| | | | - Runsheng Wang
- Columbia University Medical Center, New York, New York
| | - Ann Biehl
- National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, Bethesda, Maryland
| | - Meika A. Fang
- VA West Los Angeles Medical Center, Los Angeles, California
| | - Grant Louie
- Arthritis and Rheumatism Associates, Wheaton, Maryland
| | - Vikas Majithia
- University of Mississippi Medical Center, Jackson, Mississippi
| | - Bernard Ng
- University of Washington, Seattle, Washington
| | | | | | | | | | | | | | - Amy Turner
- American College of Rheumatology, Atlanta, Georgia
| | | | - Liron Caplan
- Rocky Mountain Regional VA Medical Center, Aurora, Colorado, and University of Colorado, Aurora, Colorado
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13
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Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, Haroon N, Borenstein D, Wang R, Biehl A, Fang MA, Louie G, Majithia V, Ng B, Bigham R, Pianin M, Shah AA, Sullivan N, Turgunbaev M, Oristaglio J, Turner A, Maksymowych WP, Caplan L. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol 2019; 71:1599-1613. [PMID: 31436036 PMCID: PMC6764882 DOI: 10.1002/art.41042] [Citation(s) in RCA: 419] [Impact Index Per Article: 69.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 07/09/2019] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. RESULTS Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. CONCLUSION These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.
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Affiliation(s)
- Michael M. Ward
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland
| | - Atul Deodhar
- Oregon Health & Science University, Portland, Oregon
| | | | | | - David Yu
- University of California, Los Angeles
| | | | - Nigil Haroon
- University of Toronto, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada
| | | | - Runsheng Wang
- Columbia University Medical Center, New York, New York
| | - Ann Biehl
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland
| | - Meika A. Fang
- VA West Los Angeles Medical Center, Los Angeles, California
| | - Grant Louie
- Arthritis and Rheumatism Associates, Wheaton, Maryland
| | - Vikas Majithia
- University of Mississippi Medical Center, Jackson, Mississippi
| | | | | | | | | | | | | | | | - Amy Turner
- American College of Rheumatology, Atlanta, Georgia
| | | | - Liron Caplan
- Rocky Mountain Regional VA Medical Center and University of Colorado, Aurora
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Oral treatment options for AS and PsA: DMARDs and small-molecule inhibitors. Best Pract Res Clin Rheumatol 2018; 32:415-426. [DOI: 10.1016/j.berh.2018.08.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 07/25/2018] [Accepted: 07/28/2018] [Indexed: 12/17/2022]
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Nair AM, Sandhya P, Yadav B, Danda D. TNFα blockers followed by continuation of sulfasalazine and methotrexate combination: a retrospective study on cost saving options of treatment in Spondyloarthritis. Clin Rheumatol 2017. [PMID: 28646368 DOI: 10.1007/s10067-017-3726-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
High cost deters continuous use of tumor necrosis factor α blockers (TNFi) in developing countries. The objective of this study was to evaluate outcome and expenditure incurred in Spondyloarthritis (SpA) patients beyond a year of follow-up after receiving four doses of infliximab (IFX) over and above background therapy of methotrexate (MTX) and sulfasalazine (SSZ) combination. Electronic medical records were screened for patients with SpA satisfying the Assessment of Spondyloarthritis International Society (ASAS) criteria between 2008 and 2014. Patients who completed at least 1 year of follow-up after receiving four doses of IFX (5 mg/kg at 0, 2, 6, and 14 weeks) on a background therapy of MTX (10-25 mg/week) and SSZ (2-3 g/day) combination were enrolled after obtaining an informed consent. Primary outcome assessed was "time to disease flare". Changes in acute phase reactants, patient reported outcomes (BASDAI, BASFI), and cost were also assessed. Forty-five patients were enrolled. Mean (SD) duration of follow up after fourth IFX dose was 28.9 (18.7) months. Disease flare occurred in 33.3% (15/45) after a mean (SD) duration of 14.5 (10.8) months as compared to 4-6 months described in literature on discontinuing TNFi. Reduction in ESR, CRP, BASDAI and BASFI continued to be statistically significant at follow-up as compared to baseline. As compared to continuous IFX therapy, this treatment reduced cost by 57.1% for each patient-month of follow-up. Short course IFX dosing followed by continuation of MTX and SSZ combination can prolong time to disease flare and decrease requirement for additional IFX dose in SpA. This regimen could be a cost saving option for patients with SpA.
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Affiliation(s)
- Aswin M Nair
- Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - P Sandhya
- Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - Bijesh Yadav
- Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India
| | - Debashish Danda
- Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, 632004, India.
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Akkoc N, Can G, D’Angelo S, Padula A, Olivieri I. Therapies of Early, Advanced, and Late Onset Forms of Axial Spondyloarthritis, and the Need for Treat to Target Strategies. Curr Rheumatol Rep 2017; 19:8. [DOI: 10.1007/s11926-017-0633-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Cipriani P, Ruscitti P, Carubbi F, Liakouli V, Giacomelli R. Methotrexate: an old new drug in autoimmune disease. Expert Rev Clin Immunol 2014; 10:1519-30. [PMID: 25245537 DOI: 10.1586/1744666x.2014.962996] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Methotrexate (MTX) is currently considered, among disease-modifying anti-rheumatic drugs (DMARDs), the 'anchor-drug' in the treatment of rheumatoid arthritis. In the last 25 years, there has been a marked expansion in the use of MTX in different inflammatory diseases. Its low cost, associated to a good long-term efficacy and safety profile, justifies the use of MTX as a first-line disease-modifying drug or alternatively, a steroid-sparing medication in this field of medicine. Although new emerging options, including biological treatments, are being established in the therapeutic scenario, the good cost/benefit ratio of MTX supports the choice of this drug in combination with these newer therapies, enhancing the efficacy of these combination therapies and decreasing the risk of potential side effects.
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Affiliation(s)
- Paola Cipriani
- Department of Biotechnological and Applied Clinical Science, Rheumatology Unit, School of Medicine, University of L'Aquila, Delta 6 Building, Via dell'Ospedale, 67100, L'Aquila, Italy
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Relas H, Kautiainen H, Puolakka K, Virta LJ, Leirisalo-Repo M. Survival of disease-modifying antirheumatic drugs used as the first antirheumatic medication in the treatment of ankylosing spondylitis in Finland. A nationwide population-based register study. Clin Rheumatol 2014; 33:1135-8. [PMID: 24907035 DOI: 10.1007/s10067-014-2700-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Revised: 05/08/2014] [Accepted: 05/23/2014] [Indexed: 01/06/2023]
Abstract
The tight national drug reimbursement regulations in the treatment of ankylosing spondylitis (AS) in Finland lead to the practice that at least one traditional disease-modifying antirheumatic drug (DMARD), if not contraindicated, has been tried and has failed before a patient can be eligible for reimbursement of anti-tumour necrosis factor (TNF) treatment. The aim of the present study is to evaluate drug survival of the firstly prescribed DMARDs in patients with AS. All AS patients from January 1, 2000 to December 31, 2007 were collected from the nationwide drug reimbursement registry maintained by the Social Insurance Institution (SII). Data on antirheumatic medication came from the prescription registry of SII. A total of 2,890 AS patients (60 % males) were identified. Sulfasalazine (SSA) monotherapy was the most common first antirheumatic treatment (2,319 patients, 87 %), followed by methotrexate (MTX) monotherapy (230 patients, 9 %) and by hydroxychloroquine monotherapy (77 patients, 3 %). A combination of two or more DMARDs was used by 44 patients (2 %). Only seven patients (0.3 %) had biological (etanercept or adalimumab) started as the first antirheumatic drug. Median survival time of SSA monotherapy was 4.5 years (95 % CI 4.2 to 4.8) and that of MTX was 1.9 years (95 % CI 1.5 to 2.1). SSA is almost the standard as the first antirheumatic treatment of AS in Finland. Although the clinical efficiency of SSA was not evaluable in the present study, these data suggest that the use of SSA can at least postpone the need and start of TNF inhibitors with marked economic consequences.
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Affiliation(s)
- Heikki Relas
- Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, PO BOX 372, FI-00029 HUS, Helsinki, Finland,
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Kohem CL, Bortoluzzo AB, Gonçalves CR, Silva JABD, Ximenes AC, Bértolo MB, Ribeiro SL, Keiserman M, Menin R, Skare TL, Carneiro S, Azevedo VF, Vieira WP, Albuquerque EN, Bianchi WA, Bonfiglioli R, Campanholo C, Carvalho HM, Costa IPD, Duarte ALP, Leite NH, Lima SA, Meirelles ES, Pereira IA, Pinheiro MM, Polito E, Resende GG, Rocha FAC, Santiago MB, Sauma MDFL, Valim V, Sampaio-Barros PD. Perfil do uso de drogas modificadoras de doença no Registro Brasileiro de Espondiloartrites. REVISTA BRASILEIRA DE REUMATOLOGIA 2014. [DOI: 10.1016/j.rbr.2013.06.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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Sieper J, Porter-Brown B, Thompson L, Harari O, Dougados M. Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials. Ann Rheum Dis 2014; 73:95-100. [PMID: 23765873 PMCID: PMC3888605 DOI: 10.1136/annrheumdis-2013-203559] [Citation(s) in RCA: 159] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/12/2013] [Indexed: 12/17/2022]
Abstract
OBJECTIVES BUILDER-1 and BUILDER-2 aimed to assess the efficacy and safety of tocilizumab (TCZ) in patients with ankylosing spondylitis (AS). METHODS BUILDER-1 was a two part, phase II-III parallel-group trial in patients with AS naive to antitumour necrosis factor (aTNF) treatment. Patients in part 1 received TCZ 8 mg/kg or placebo for 12 weeks. In part 2 (beginning after part 1 enrolment ended), newly enrolled patients received TCZ 4 or 8 mg/kg or placebo for 24 weeks. The same treatment arms were used in BUILDER-2, a phase III study in aTNF-inadequate responders. The primary endpoint for both studies was the proportion of patients achieving 20% improvement in the Assessments in Axial SpondyloArthritis international Society (ASAS). Secondary and exploratory endpoints included ASAS40 response rates, Bath Ankylosing Spondylitis Disease Activity Index improvement, changes in joint counts, enthesitis score and C reactive protein (CRP). RESULTS 102 patients were randomised in BUILDER-1 part 1; 99 (48 TCZ, 51 placebo) completed 12 weeks. Week 12 ASAS20 response rates were 37.3% and 27.5% in the TCZ and placebo arms, respectively (p=0.2823). Secondary and exploratory endpoints did not differ between treatment arms. CRP levels declined with TCZ treatment, suggesting adequate IL-6 receptor blockade. As a result, BUILDER-1 part 2 and BUILDER-2 were terminated. TCZ safety results were consistent with previous observations in rheumatoid arthritis, except for a cluster of anaphylactic and hypersensitivity events at Bulgarian study sites. No apparent explanation for this clustering could be found. CONCLUSIONS BUILDER-1 failed to demonstrate TCZ efficacy in treating aTNF-naive patients with AS.
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Affiliation(s)
- Joachim Sieper
- Department of Medicine 1, Rheumatology, Charité Universitätsmedizin, Berlin, Germany
| | | | | | | | - Maxime Dougados
- Department of Rheumatology B, René Descartes University-Paris 5 and Cochin Hospital, Paris, France
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Abstract
BACKGROUND Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterized by sacroiliitis and spondylitis. Methotrexate (MTX), a widely used disease-modifying antirheumatic drug (DMARD), is effective for rheumatoid arthritis (RA), and so might work for AS. This is an update of a Cochrane review first published in 2004, and previously updated in 2006. OBJECTIVES To evaluate the benefits and harms of MTX for treating AS. SEARCH METHODS We searched CENTRAL (The Cochrane Library Issue 6, 2012), MEDLINE (2005 to June 25, 2012), EMBASE (2005 to June 25, 2012), Ovid MEDLINE Scopus, World Health Organization International Clinical Trials Registry Platform and the reference sections of retrieved articles. Trials published in any language were acceptable. SELECTION CRITERIA Randomized controlled trials (RCTs) and quasi-randomized controlled trials (qRCTs) examining the benefits and harms of MTX versus placebo, other medication, or no medication for treatment of AS. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed risk of bias. We resolved any disagreements through discussions with a third review author. In the absence of significant heterogeneity, we combined results for continuous data using mean difference or standardized mean difference values. We calculated the risk ratio for dichotomous data. MAIN RESULTS We identified three RCTs (no additional new studies), which included 116 participants. Of these three trials, one was a 12-month trial that compared naproxen plus MTX with naproxen alone. Also, there were two 24-week trials that compared different doses of MTX with placebo. We included the outcomes of response, physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs, and patient and physician global assessment. We judged only one trial to be at low risk of bias. Across these three trials, we did not identify any statistically significant differences favoring MTX treatment over no MTX treatment apart from one exception. The response rate in one trial showed a statistically significant absolute benefit of 36% and a number to treat for benefit (NNT) of three in the MTX group compared to the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was based on a composite index that included assessments of morning stiffness, physical well-being, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire for spondyloarthropathies (HAQ-S), and physician and patient global assessment. We did not identify any outcome that showed a statistically significant difference between the MTX treated and no MTX treatment groups when endpoint results were compared. Furthermore, no serious side effects were reported in any of the included trials. AUTHORS' CONCLUSIONS There is not enough evidence to support any benefit of MTX in the treatment of AS. High-quality RCTs of larger sample sizes are needed to clarify the effect(s) of MTX on AS.
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Affiliation(s)
- Junmin Chen
- Department of Hematology and Rheumatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
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Non-biologic disease-modifying antirheumatic drugs (DMARDs) improve pain in inflammatory arthritis (IA): a systematic literature review of randomized controlled trials. Rheumatol Int 2013; 33:1105-20. [PMID: 23292213 DOI: 10.1007/s00296-012-2619-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2012] [Accepted: 12/09/2012] [Indexed: 01/06/2023]
Abstract
Evidence supports early use of non-biologic DMARDs to prevent irreversible damage in inflammatory arthritides, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and possibly ankylosing spondylitis (AS). However, there is a paucity of data exploring their effects on pain as a primary outcome in these conditions. This systematic literature review investigated the effect of non-biologic DMARDs on pain levels in IA and examined whether disease duration impacted efficacy. We searched Medline, Embase, Cochrane Central, and Cochrane Database of Systematic Reviews, abstracts from the 2008 to 2010 American College of Rheumatology annual congresses, and citation lists of retrieved publications. Only randomized, double-blind controlled trials were analyzed. Quality was assessed with the Risk of Bias tool. Descriptive statistics were used in meta-analysis. 9,860 articles were identified, with 33 eligible for inclusion: 8 in AS, 6 in PsA, 9 in early RA (ERA), and 10 in established RA. In ERA and established RA, all studies of DMARDs (monotherapy and combination therapies) consistently revealed statistically significant reductions in pain except three oral gold studies. In AS, sulfasalazine studies showed significant pain reduction, whereas use of other DMARDs did not. In PsA, 5 of 6 studies reported VAS-pain improvement. From the studies included, we were unable to assess the influence of disease duration on pain outcomes in these rheumatic conditions. DMARDs improve pain in early and established RA. Sulfasalazine may improve pain in AS and PsA. Further study is needed to assess the relationship between disease duration and DMARD efficacy in reducing pain in these conditions.
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Can M, Aydın SZ, Niğdelioğlu A, Atagündüz P, Direskeneli H. Conventional DMARD therapy (methotrexate-sulphasalazine) may decrease the requirement of biologics in routine practice of ankylosing spondylitis patients: A real-life experience. Int J Rheum Dis 2012; 15:526-30. [DOI: 10.1111/j.1756-185x.2012.01817.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- Meryem Can
- Department of Rheumatology; Pendik Training and Research Hospital; Marmara University; Istanbul; Turkey
| | - Sibel Z. Aydın
- Rheumatology Unit; Istanbul Medeniyet University; Goztepe Training and Research Hospital, Istanbul, Turkey; Istanbul; Turkey
| | - Adil Niğdelioğlu
- Department of Internal Medicine; Pendik Training and Research Hospital; Marmara University; Istanbul; Turkey
| | - Pamir Atagündüz
- Department of Rheumatology; Pendik Training and Research Hospital; Marmara University; Istanbul; Turkey
| | - Haner Direskeneli
- Department of Rheumatology; Pendik Training and Research Hospital; Marmara University; Istanbul; Turkey
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Colebatch AN, Marks JL, Edwards CJ. Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis). Cochrane Database Syst Rev 2011:CD008872. [PMID: 22071858 DOI: 10.1002/14651858.cd008872.pub2] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Methotrexate is routinely used in the treatment of inflammatory arthritis. There have been concerns regarding the safety of using concurrent non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, or paracetamol (acetaminophen), or both, in these people. OBJECTIVES To systematically appraise and summarise the scientific evidence on the safety of using NSAIDs, including aspirin, or paracetamol, or both, with methotrexate in inflammatory arthritis; and to identify gaps in the current evidence, assess the implications of those gaps and to make recommendations for future research to address these deficiencies. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, second quarter 2010); MEDLINE (from 1950); EMBASE (from 1980); the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE). We also handsearched the conference proceedings for the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) (2008 to 2009) and checked the websites of regulatory agencies for reported adverse events, labels and warnings. SELECTION CRITERIA Randomised controlled trials and non-randomised studies comparing the safety of methotrexate alone to methotrexate with concurrent NSAIDs, including aspirin, or paracetamol, or both, in people with inflammatory arthritis. DATA COLLECTION AND ANALYSIS Two authors independently assessed the search results, extracted data and assessed the risk of bias of the included studies. MAIN RESULTS Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis using various NSAIDs, including aspirin. There were no identified studies for other forms of inflammatory arthritis.For NSAIDs, 13 studies were included that used concurrent NSAIDs, of which nine studies examined unspecified NSAIDs. The mean number of participants was 150.4 (range 19 to 315), mean duration 2182.9 (range 183 to 5490) days, although the study duration was not always clearly defined, and the studies were mainly of low to moderate quality. Two of these studies reported no evidence for increased risk of methotrexate-induced pulmonary disease; one study assessed the effect of concurrent NSAIDs on renal function and found no adverse effect; one study identified no adverse effect on liver function; three studies demonstrated no increase in methotrexate withdrawal; and one study showed no increase in all adverse events, including major toxic reactions. However, transient thrombocytopenia was demonstrated in one study, specifically when NSAIDs were taken on the same week day as methotrexate. This study was a retrospective review that involved small numbers only and was of moderate quality; these finding have not been replicated since.Four studies looked at specific NSAIDs (etodolac, piroxicam, celecoxib and etoricoxib), with a mean number of participants of 25.8 (range 14 to 50) and mean study duration of 16.8 (range 14 to 23) days. These studies were mainly of moderate quality. The studies were primarily pharmacokinetic studies but also reported adverse events as secondary outcomes. There were no clinically significant adverse effects with concomitant piroxicam or etodolac; and only mild adverse events with celecoxib or etoricoxib, such as nausea and vomiting, and headaches.For aspirin, seven studies provided data on adverse events with the use of aspirin and methotrexate. These studies included a mean number of participants of 100 (range 11 to 232), had a mean duration of 1325 (range 8 to 2928) days and were mainly of low to moderate quality. Two of the studies reported no evidence for increased risk of methotrexate-induced pulmonary disease and two studies showed no increase in all adverse events including major toxic reactions; however, none of these studies specified the dose of aspirin that was used. One study demonstrated that concurrent aspirin adversely affected liver function at a mean dose of 6.84 tablets of aspirin per day, which is a possible daily dose of 2.1 g presuming that 300 mg aspirin tablets were given. A further study described a partially reversible decline in renal function with 2 g daily of aspirin. One study reported no increase in adverse events with 975 g aspirin daily, however the study duration was only one week.For paracetamol, no studies were identified for inclusion. AUTHORS' CONCLUSIONS In the management of rheumatoid arthritis, the concurrent use of NSAIDs with methotrexate appears to be safe provided appropriate monitoring is performed. The use of anti-inflammatory doses of aspirin should be avoided.
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Affiliation(s)
- Alexandra N Colebatch
- Department of Rheumatology, Southampton General Hospital, Southampton; Consultant Rheumatologist Yeovil District Hospital,Somerset, UK.
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Mulleman D, Lauféron F, Wendling D, Ternant D, Ducourau E, Paintaud G, Goupille P. Infliximab in ankylosing spondylitis: alone or in combination with methotrexate? A pharmacokinetic comparative study. Arthritis Res Ther 2011; 13:R82. [PMID: 21639907 PMCID: PMC3218893 DOI: 10.1186/ar3350] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2011] [Revised: 03/21/2011] [Accepted: 06/03/2011] [Indexed: 12/19/2022] Open
Abstract
INTRODUCTION Methotrexate (MTX) has been shown to modify infliximab pharmacokinetics in rheumatoid arthritis. However, its combination with infliximab in the treatment of ankylosing spondylitis (AS) is not recommended. The objective of this study was to examine the influence of MTX on infliximab exposure in patients with AS. METHODS Patients with AS patients who had predominantly axial symptoms were randomised to receive infliximab alone (infusions of 5 mg/kg at weeks 0, 2, 6, 12 and 18) or infliximab combined with MTX (10 mg/week). Infliximab concentrations were measured before and 2 hours after each infusion and at 1, 3, 4, 5, 8, 10, 14 and 18 weeks. We estimated individual cumulative area under the concentration versus time curves (AUC) for infliximab concentration between baseline and week 18 (AUC(0-18)). Clinical and laboratory evaluations were performed at each visit. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was the primary end point for clinical response. RESULTS Twenty-six patients were included (infliximab group: n = 12, infliximab + MTX group: n = 14), and 507 serum samples were available for measurement of infliximab concentration. The two groups did not differ with regard to AUC(0-18) or evolution of BASDAI scores and biomarkers of inflammation. CONCLUSIONS The combination of MTX and infliximab does not increase the exposure to infliximab over infliximab alone in patients with AS. TRIAL REGISTRATION ClinicalTrials.gov: NCT00507403.
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Affiliation(s)
- Denis Mulleman
- Université François-Rabelais de Tours, Centre National de la Recherche Scientifique UMR 6239 GICC (Génétique Immunothérapie Chimie et Cancer), 3 rue des Tanneurs, F-37041 Tours Cedex 1, France
- Service de Rhumatologie, Centre Hospitalier Régional et Universitaire de Tours, avenue de la République, F-37044 Tours Cedex 9, France
| | - Francine Lauféron
- Université François-Rabelais de Tours, Centre National de la Recherche Scientifique UMR 6239 GICC (Génétique Immunothérapie Chimie et Cancer), 3 rue des Tanneurs, F-37041 Tours Cedex 1, France
- Service de Rhumatologie, Centre Hospitalier Régional et Universitaire de Tours, avenue de la République, F-37044 Tours Cedex 9, France
| | - Daniel Wendling
- Université de Franche-Comté, EA 4266 API (Agents Pathogènes et Inflammation), Hôpital Saint Jacques, 2 place Saint-Jacques, F-25030 Besançon Cedex, Besançon, France
- Service de Rhumatologie, Centre Hospitalier Régional et Universitaire de Besançon, Hôpital Jean Minjoz, 3 boulevard Alexander Fleming, F-25030 Besançon Cedex, Besançon, France
| | - David Ternant
- Université François-Rabelais de Tours, Centre National de la Recherche Scientifique UMR 6239 GICC (Génétique Immunothérapie Chimie et Cancer), 3 rue des Tanneurs, F-37041 Tours Cedex 1, France
- Laboratoire de Pharmacologie-Toxicologie, Centre Hospitalier Régional et Universitaire de Tours, 2 boulevard Tonnellé, F-37044 Tours Cedex 9, France
| | - Emilie Ducourau
- Université François-Rabelais de Tours, Centre National de la Recherche Scientifique UMR 6239 GICC (Génétique Immunothérapie Chimie et Cancer), 3 rue des Tanneurs, F-37041 Tours Cedex 1, France
- Service de Rhumatologie, Centre Hospitalier Régional et Universitaire de Tours, avenue de la République, F-37044 Tours Cedex 9, France
| | - Gilles Paintaud
- Université François-Rabelais de Tours, Centre National de la Recherche Scientifique UMR 6239 GICC (Génétique Immunothérapie Chimie et Cancer), 3 rue des Tanneurs, F-37041 Tours Cedex 1, France
- Laboratoire de Pharmacologie-Toxicologie, Centre Hospitalier Régional et Universitaire de Tours, 2 boulevard Tonnellé, F-37044 Tours Cedex 9, France
| | - Philippe Goupille
- Université François-Rabelais de Tours, Centre National de la Recherche Scientifique UMR 6239 GICC (Génétique Immunothérapie Chimie et Cancer), 3 rue des Tanneurs, F-37041 Tours Cedex 1, France
- Service de Rhumatologie, Centre Hospitalier Régional et Universitaire de Tours, avenue de la République, F-37044 Tours Cedex 9, France
- Institut National de la Santé et de la Recherche Médicale CIC 202, 2 boulevard Tonnellé, F-37044 Tours Cedex 9, Tours, France
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Sieper J. Management of ankylosing spondylitis. Rheumatology (Oxford) 2011. [DOI: 10.1016/b978-0-323-06551-1.00116-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
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Malaviya AN, Shankar S, Arya V, Dhir V, Agarwal V, Pandya S, Shanmuganandan K, Chaturvedi VP, Das CJ. Indian Rheumatology Association consensus statement on the diagnosis and treatment of axial spondyloarthropathies. INDIAN JOURNAL OF RHEUMATOLOGY 2010; 5:16-34. [DOI: 10.1016/s0973-3698(10)60531-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Braun J, Zochling J, Märker-Hermann E, Stucki G, Böhm H, Rudwaleit M, Zeidler H, Sieper J. [Recommendations for the management of ankylosing spodylitis after ASAS/EULAR. Evaluation in the German language area]. Z Rheumatol 2009; 65:728-42. [PMID: 17119900 DOI: 10.1007/s00393-006-0119-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
AIM Our aim was to adapt and implement the evidence based recommendations for the management of ankylosing spodylitis (AS) of the "Assessments in AS" (ASAS) International Working Group together with the European League Against Rheumatism (EULAR) within the framework of a competence network (CN) in rheumatology in the German language area. METHODS The ASAS/EULAR project calculated the effective size (ES), rate ratio, number of patients requiring treatment (number needed to treat, NNT) and the incremental cost-effectiveness ratio (ICER). The strength of the recommendations was determined through the evidence level found in the literature, the risk-benefit trade-off and the clinical experience of the experts. The recommendations were recently published in English. All of the centers taking part in the study area Spondyloarthritis (SpA) CN, as well as an additional 35 experts, were sent the English manuscript. All 35 participants were asked to evaluate the ten main management recommendations on a scale from 0 to 10. RESULTS The recommendations encompass the use of drugs such as non-steroid anti-inflammatories (NSAR), which, along with conventional NSAR include coxibs and the parallel application of gastroprotectives, so called disease-modifying anti-rheumatic drugs, biologicals, simple analgesics, local and systematic glucocorticoids, non-drug therapies (such as patient training, medical training therapy and physiotherapy), in addition to surgical treatment methods. Moreover, three general recommendations were formulated and a therapy scheme created, taking into consideration the various clinical manifestations. The strength of the ASAS/EULAR recommendations was generally high. There was a marked consensus between the German speaking experts and the international proposal: a mean of 9.13 with relatively low variation between the recommendations. SUMMARY Ten key recommendations for the treatment of AS were developed. These were strengthened by a systematic search of the literature and by expert consensus. The large group of German speaking experts were largely in agreement with the proposal. This can be seen as a starting point for the dissemination and implementation of the recommendations.
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Affiliation(s)
- J Braun
- Rheumazentrum-Ruhrgebiet, St. Josefs-Krankenhaus, Landgrafenstrasse 15, 44652, Herne, Deutschland.
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Goh L, Samanta A. A systematic MEDLINE analysis of therapeutic approaches in ankylosing spondylitis. Rheumatol Int 2009; 29:1123-35. [PMID: 19562344 DOI: 10.1007/s00296-009-0973-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2008] [Accepted: 05/20/2009] [Indexed: 12/17/2022]
Abstract
Ankylosing spondylitis (AS) is a chronic inflammatory disorder involving the sacroiliac joints (SIJs), spine and less frequently the peripheral joints. Traditionally, it is well recognised that AS is a challenging disease to manage due to the lack of effective therapeutic options. Current evidence would suggest this has changed and there are now a number of therapies available that provide persistent control of inflammatory symptoms with improvement in daily function. NSAIDs remain the first step in patient treatment. Sulphasalazine may be effective in peripheral arthritis and there are emerging data to support its use in early inflammatory back pain. Studies have shown that pamidronate and steroid injection into SIJ have a symptom-modifying effect in AS. Current data suggest that anti-TNF treatment promises early benefit which is likely to continue in the longer term. Treatment with biologics should be considered sooner rather than later in the management of AS.
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Affiliation(s)
- L Goh
- Department of Rheumatology, Musgrove Park Hospital, Taunton and Somerset NHS Trust, Taunton, TA1 5DA, UK.
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Olivieri I, D'Angelo S, Palazzi C, Padula A. Treatment strategies for early psoriatic arthritis. Expert Opin Pharmacother 2009; 10:271-82. [PMID: 19236198 DOI: 10.1517/14656560802653198] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Until a few years ago, the early diagnosis of psoriatic arthritis (PsA) did not receive much attention, especially in view of the lack of drugs capable of altering the disease course. This changed with the introduction of the TNF-alpha-blocking agents, as a result of which the early diagnosis of PsA is now a topic of great interest. OBJECTIVE The aim of the study was to review the treatment for PsA in order to determine the optimal approach to managing early disease. METHODS The systematic review performed by members of GRAPPA (Group of Research and Assessment of Psoriasis and Psoriatic Arthritis) was integrated with data from more recent studies. RESULTS/CONCLUSION After making the diagnosis of PsA, the next step is to stage of the disease with the aim of establishing the prevalent manifestation (peripheral arthritis, peripheral enthesitis, axial involvement and dactylitis) and degree of severity (mild, moderate or severe) of the disease. Each patient should be treated according to the defined disease status following the suggested treatment algorithms.
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Affiliation(s)
- Ignazio Olivieri
- San Carlo Hospital of Potenza, Rheumatology Department Contrada Macchia Romana, 85100, Potenza, Italy.
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Li EK, Griffith JF, Lee VW, Wang YX, Li TK, Lee KK, Tam LS. Short-term efficacy of combination methotrexate and infliximab in patients with ankylosing spondylitis: a clinical and magnetic resonance imaging correlation. Rheumatology (Oxford) 2008; 47:1358-63. [DOI: 10.1093/rheumatology/ken207] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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Sidiropoulos PI, Hatemi G, Song IH, Avouac J, Collantes E, Hamuryudan V, Herold M, Kvien TK, Mielants H, Mendoza JM, Olivieri I, Østergaard M, Schachna L, Sieper J, Boumpas DT, Dougados M. Evidence-based recommendations for the management of ankylosing spondylitis: systematic literature search of the 3E Initiative in Rheumatology involving a broad panel of experts and practising rheumatologists. Rheumatology (Oxford) 2008; 47:355-61. [PMID: 18276738 DOI: 10.1093/rheumatology/kem348] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
OBJECTIVE Recommendations and/or guidelines represent a popular way of integrating evidence-based medicine into clinical practice. The 3E Initiatives is a multi-national effort to develop recommendations for the management of rheumatic diseases, which involves a large number of experts combined with practising rheumatologists addressing specific questions relevant to clinical practice. METHODS Ten countries participated in three rounds of discussions and votes concerning the management of AS. A set of nine questions was formulated in the domains of diagnosis, monitoring and treatment, after a Delphi procedure. A literature search in MedLine was conducted. Predefined outcome parameters for the domains of diagnosis, monitoring and treatment were assessed. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements by each national group, following which the final international recommendations were formulated. RESULTS A total of 2699 papers were found and 467 were selected for analysis. Twelve key recommendations were developed: three in the domain of diagnosis addressing general diagnostic considerations, early AS diagnosis and general practitioners' referral recommendations; three concerning monitoring of AS disease activity, severity and prognosis; six concerning pharmacological treatment (except biologics): non-steroidal anti-inflammatory drugs/COX-II inhibitors, bisphosphonates and treatment of enthesitis. The compiled agreement among experts ranged from 72% to 93%. CONCLUSION Recommendations for the management of AS were developed using an evidence-based approach followed by expert/physician consensus with high level of agreement. Involvement of a larger and more representative group of rheumatologists may improve their dissemination and implementation in daily clinical practice.
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Affiliation(s)
- P I Sidiropoulos
- Department of Internal Medicine, Division of Rheumatology, Clinical Immunology and Allergy, University of Crete, Medical School, Voutes 71500, Heraklion, Greece.
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Therapy Insight: how the gut talks to the joints—inflammatory bowel disease and the spondyloarthropathies. ACTA ACUST UNITED AC 2007; 3:667-74. [DOI: 10.1038/ncprheum0625] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2007] [Accepted: 07/31/2007] [Indexed: 12/18/2022]
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Konttinen L, Tuompo R, Uusitalo T, Luosujärvi R, Laiho K, Lähteenmäki J, Puurtinen-Vilkki M, Lanteri R, Kortelainen S, Karilainen H, Varjolahti-Lehtinen T, Nordström D. Anti-TNF therapy in the treatment of ankylosing spondylitis: the Finnish experience. Clin Rheumatol 2007; 26:1693-700. [PMID: 17332979 DOI: 10.1007/s10067-007-0574-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2006] [Revised: 01/26/2007] [Accepted: 01/26/2007] [Indexed: 12/12/2022]
Abstract
Biological therapy for ankylosing spondylitis (AS) has led to improved disease control beyond that of conventional treatments. International recommendations encourage clinicians prescribing biological treatments to register patients in national registers to collect information on outcome and toxicity. Patients with AS (n = 229) from the Register of Biological Treatment in Finland (ROB-FIN) with severe disease of long duration were followed-up for up to 24 months. Due to an active disease, one or more concomitant disease-modifying antirheumatic drugs (DMARDs) were used by 86% at commencement of biological therapy. This add-on strategy with infliximab led to a rapid pain relief and improvement of patient's and physician's global assessments, C-reactive protein/erythrocyte sedimentation rate, and swollen and tender joint counts within 6 weeks. Concomitant use of NSAID and oral corticosteroid was reduced. Corresponding results were documented at 3 months with etanercept, which was more recently approved for the treatment of spondyloarthropathies. Seventy-nine percent of the patients were ASAS 20 responders. A subgroup of AS patients with only axial involvement (n = 46) responded correspondingly. The first biological drug was discontinued in only 7% due to lack of efficacy and in 6% due to adverse events. Anti-TNF agents, often used in combination with DMARDs, appeared to have persistent effectiveness and limited toxicity in a real-life clinical setting in a cohort of Finnish AS patients with severe disease and long disease duration.
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Haibel H, Brandt HC, Song IH, Brandt A, Listing J, Rudwaleit M, Sieper J. No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial. Ann Rheum Dis 2007; 66:419-21. [PMID: 16901959 PMCID: PMC1856012 DOI: 10.1136/ard.2006.054098] [Citation(s) in RCA: 141] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/19/2006] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To examine the potential therapeutic effect of methotrexate 20 mg given weekly as subcutaneous injections to 20 patients with ankylosing spondylitis refractory to non-steroidal antirheumatic drugs. PATIENTS AND METHODS 20 patients with ankylosing spondylitis, a mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 5.6 (range 4-9.3) and predominantly axial manifestations were treated with weekly 15 mg methotrexate subcutaneously for 4 weeks, which was then increased to 20 mg subcutaneously for the next 12 weeks. Clinical outcome assessments included, among others, BASDAI score physical function, spinal mobility, patients' and physicians' global assessment (visual analogue scale), peripheral joint assessment, quality of life (Short Form 36) and C reactive protein. The primary end point of the study was a 20% improvement on the ASsessments in Ankylosing Spondylitis (ASAS 20) scale. RESULTS Using an intention-to-treat analysis, ASAS 20 was achieved in only 25% of patients. An ASAS 40 response was achieved in 10% of patients, and no patient reached an ASAS 70 response or the ASAS criteria for partial remission. For the mean BASDAI score, no change was observed between baseline and week 16 (baseline 5.6 v week 16, 5.6). No improvement was observed in any of the clinical parameters or C reactive protein, except a small but non-significant decrease in the number of swollen joints. CONCLUSIONS In this open study, methotrexate did not show any benefit for axial manifestations in patients with active ankylosing spondylitis beyond the expected placebo response.
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Affiliation(s)
- H Haibel
- Medical Department I, Rheumatology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
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Akkoc N, van der Linden S, Khan MA. Ankylosing spondylitis and symptom-modifying vs disease-modifying therapy. Best Pract Res Clin Rheumatol 2006; 20:539-57. [PMID: 16777581 DOI: 10.1016/j.berh.2006.03.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The main objectives of medical therapy in ankylosing spondylitis (AS) are to relieve pain, stiffness and fatigue and to prevent structural damage. The Assessment in Ankylosing Spondylitis Working Group has proposed different domains with specific instruments to assess the efficacy of therapeutic agents classified as symptom-modifying and disease-controlling antirheumatic drugs. Non-steroidal antiinflammatory drugs (NSAIDs) are still the first-line treatment in the management of AS, and they are effective in controlling symptoms such as pain and stiffness and maintaining mobility in many patients. A recent randomized trial suggested that the progression of radiological damage occurs less on continuous use of celecoxib compared with on-demand use. If such findings were confirmed by other studies, the therapeutic value of NSAIDs in AS may extend beyond symptom control. However, for each individual patient, the expected advantages of treatment with NSAIDs should be weighted against any possible gastrointestinal and cardiovascular disadvantages. Disease-modifying antirheumatic drugs (DMARDs) are widely used for second-line therapy in AS, but the evidence for their efficacy is poor. The term 'DMARD' has been borrowed from rheumatoid arthritis, and none of the DMARDs have been shown to prevent or significantly decrease the rate of progression of structural damage which is required to be qualified as a disease-controlling antirheumatic drug for AS. Sulphasalazine is the most extensively studied DMARD and studies suggest some degree of clinical benefit confined to peripheral joint involvement, but no evidence of benefit in axial disease. Methotrexate, which is the gold standard DMARD in rheumatoid arthritis, does not seem to have a substantial therapeutic effect in AS on axial or peripheral joint involvement. Leflunomide appears to exert little beneficial effect, if any, even on peripheral joint involvement. There is also good evidence that local therapy with corticosteroids is effective and may be used in selected patients. Oral corticosteroids may be somewhat effective in relieving the symptoms of AS, but this has not been formally studied. Small studies have reported favourable results with intravenous methylprednisolone pulse therapy, but the effect is temporary. Pamidronate and thalidomide have been used in some preliminary trials but need further studies to assess their potential role in treating AS patients resistant or intolerant to other forms of treatment. Treatment with tumour necrosis factor blockers is not discussed in this review.
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Affiliation(s)
- Nurullah Akkoc
- Department of Internal Medicine, Division of Rheumatology and Immunology, Dokuz Eylul University School of Medicine, Balcova, 35340 Izmir, Turkey.
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Abstract
BACKGROUND Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterised by sacroiliitis and spondylitis. Generally, treatment is limited to the alleviation of symptoms using non-steroidal anti-inflammatory drugs (NSAIDs). Recently, disease-modifying antirheumatic drugs (DMARDs) have been used for patients for whom NSAIDs do not work. Methotrexate (MTX), a widely used DMARD, is effective for rheumatoid arthritis (RA), and so might work for AS too. OBJECTIVES To evaluate the efficacy and toxicity of MTX for treating AS. SEARCH STRATEGY We conducted searches in any language in: CENTRAL (The Cochrane Library Issue 4, 2005); MEDLINE (1966 to November 20, 2005); EMBASE (1980 to November 20, 2005); CINAHL (1982 to November 20, 2005), and the reference sections of retrieved articles. SELECTION CRITERIA Randomised and quasi-randomised trials examining the efficacy of MTX versus placebo, other medication, or no medication, for AS. DATA COLLECTION AND ANALYSIS Two reviewers independently assessed unblinded trial reports for inclusion, assessed methodological quality and entered trial data into RevMan 4.2 using the double-entry facility. Disagreements were resolved by a third reviewer. In the absence of significant heterogeneity, results for continuous data were combined using weighted mean difference or standardised mean difference. Relative risk was used for dichotomous data. MAIN RESULTS Three trials, involving 116 patients, were included. One 12-month trial compared naproxen plus MTX with naproxen alone. Two 24-week trials compared different doses of MTX with placebo. No statistically significant differences were found for the primary outcome measures of physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs and patient and physician global assessment. Only the response rate in one trial showed a statistically significant benefit of 36% in the MTX group compared to the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was a composite index that included assessments of morning stiffness, physical well-being, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire for spondyloarthropathies (HAQ-S), and physician and patient global assessment. However, no single outcome showed a statistically significant difference between the MTX and placebo groups when endpoint results were compared. Therefore, this benefit of MTX is questionable. No serious side effects were reported in these trials. AUTHORS' CONCLUSIONS There is not enough evidence to support any benefit of MTX in the treatment of AS. High-quality randomised controlled trials of longer durations and with larger sample sizes are needed to clarify the effect(s) of MTX on AS.
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Affiliation(s)
- J Chen
- TheFirst Affiliated Hospital of Fujian Medical University, Department of Hematology and Rheumatology, Fuzhou, Fujian Province, China.
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Zochling J, Braun J. Developments and current pharmacotherapeutic recommendations for ankylosing spondylitis. Expert Opin Pharmacother 2006; 7:869-83. [PMID: 16634710 DOI: 10.1517/14656566.7.7.869] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The introduction of anti-TNFalpha therapy into the field of rheumatology has led to dramatic improvements in patient care, perhaps the most remarkable being in the management of ankylosing spondylitis. As experience with these compounds grows, their place in therapeutic strategy is becoming clearer, and it has been possible to develop evidence- and expertise-based recommendations for the management of ankylosing spondylitis to aid the clinician in patient care. This review outlines treatment advances in ankylosing spondylitis, including the use of anti-TNFalpha agents, and how these have been incorporated into clinical recommendations for daily use.
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Affiliation(s)
- Jane Zochling
- Rheumazentrum-Ruhrgebiet, Landgrafenstr. 15, 44652 Herne, Germany.
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Zochling J, van der Heijde D, Dougados M, Braun J. Current evidence for the management of ankylosing spondylitis: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Ann Rheum Dis 2006; 65:423-32. [PMID: 16126792 PMCID: PMC1798100 DOI: 10.1136/ard.2005.041129] [Citation(s) in RCA: 140] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/22/2005] [Indexed: 01/06/2023]
Abstract
OBJECTIVE To assess available management strategies in ankylosing spondylitis (AS) using a systematic approach, as a part of the development of evidence based recommendations for the management of AS. METHODS A systematic search of Medline, Embase, CINAHL, PEDro, and the Cochrane Library was performed to identify relevant interventions for the management of AS. Evidence for each intervention was categorised by study type, and outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, rate ratio, number needed to treat, and incremental cost effectiveness ratio were calculated for each intervention where possible. Results from randomised controlled trials were pooled where appropriate. RESULTS Both pharmacological and non-pharmacological interventions considered to be of interest to clinicians involved in the management of AS were identified. Good evidence (level Ib) exists supporting the use of non-steroidal anti-inflammatory drugs (NSAIDs) and coxibs for symptomatic treatment. Non-pharmacological treatments are also supported for maintaining function in AS. The use of conventional antirheumatoid arthritis drugs is not well supported by high level research evidence. Tumour necrosis factor inhibitors (infliximab and etanercept) have level Ib evidence supporting large treatment effects for spinal pain and function in AS over at least 6 months. Level IV evidence supports surgical interventions in specific patients. CONCLUSION This extensive literature review forms the evidence base considered in the development of the new ASAS/EULAR recommendations for the management of AS.
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Affiliation(s)
- J Zochling
- Rheumazentrum-Ruhrgebiet, St Josefs-Krankenhaus, Landgrafenstr 15, 44652 Herne, Germany
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Zochling J, van der Heijde D, Burgos-Vargas R, Collantes E, Davis JC, Dijkmans B, Dougados M, Géher P, Inman RD, Khan MA, Kvien TK, Leirisalo-Repo M, Olivieri I, Pavelka K, Sieper J, Stucki G, Sturrock RD, van der Linden S, Wendling D, Böhm H, van Royen BJ, Braun J. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2006; 65:442-52. [PMID: 16126791 PMCID: PMC1798102 DOI: 10.1136/ard.2005.041137] [Citation(s) in RCA: 442] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/22/2005] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the 'ASsessment in AS' international working group and the European League Against Rheumatism. METHODS Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. RESULTS The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I-IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. CONCLUSION Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.
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Affiliation(s)
- J Zochling
- Rheumazentrum-Ruhrgebiet, St Josefs-Krankenhaus, Landgrafenstr 15, 44652 Herne, Germany
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Danese S, Semeraro S, Papa A, Roberto I, Scaldaferri F, Fedeli G, Gasbarrini G, Gasbarrini A. Extraintestinal manifestations in inflammatory bowel disease. World J Gastroenterol 2006; 11:7227-36. [PMID: 16437620 PMCID: PMC4725142 DOI: 10.3748/wjg.v11.i46.7227] [Citation(s) in RCA: 225] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) can be really considered to be systemic diseases since they are often associated with extraintestinal manifestations, complications, and other autoimmune disorders. Indeed, physicians who care for patients with ulcerative colitis and Crohn's disease, the two major forms of IBD, face a new clinical challenge every day, worsened by the very frequent rate of extraintestinal complications. The goal of this review is to provide an overview and an update on the extraintestinal complications occurring in IBD. Indeed, this paper highlights how virtually almost every organ system can be involved, principally eyes, skin, joints, kidneys, liver and biliary tracts, and vasculature (or vascular system) are the most common sites of systemic IBD and their involvement is dependent on different mechanisms.
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Affiliation(s)
- Silvio Danese
- Department of Internal Medicine, Catholic University School of Medicine, L.go Vito 1, Rome 00168, Italy.
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Abstract
Inflammatory bowel disease (IBD) is a common medical problem in the United States. There may be a genetic predisposition for the development of IBD. Gastrointestinal (GI) symptoms of IBD are often accompanied by symptoms in other body systems. Joint complaints are commonly noted in IBD patients, and may be the primary presenting complaint in some. The sports medicine physician must keep a high index of suspicion for IBD arthropathy in athletes who present with axial arthropathy or peripheral arthropathy that is not related to injury or overuse. Diagnosis may be difficult and relies on accurate diagnosis of the GI disease. Joint symptoms usually respond to treatment of the bowel disease. Other standard treatments of joint pain include ice, rest, rehabilitation exercises, and analgesics, although nonsteroidal anti-inflammatory drugs should be avoided as they may lead to a worsening of the GI symptoms. Exercise won't likely worsen IBD symptoms but whether exercise prevents IBD is still an area of debate.
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Affiliation(s)
- James L Moeller
- Sports Medicine Associates, PLC, 3121 University Drive, Auburn Hills, MI 48326, USA
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Braun J, Baraliakos X, Godolias G, Böhm H. Therapy of ankylosing spondylitis--a review. Part I: Conventional medical treatment and surgical therapy. Scand J Rheumatol 2005; 34:97-108. [PMID: 16095004 DOI: 10.1080/03009740510018679] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The main outcome parameters in AS and other SpA are pain, disease activity, function, spinal mobility, and structural progression. There are several treatment options, which differ, depending on the localization and severity of the manifestation and the degree of structural changes already present. There is a basic role for physiotherapy to improve and maintain spinal mobility and function and prevent handicap. The basis for drug therapy in AS is NSAIDs, which may also have an influence on structural progression. DMARDs are mainly used in cases with peripheral arthritis. Corticosteroids have a clear role for intra-articular therapy, while the role for systemic use is, in contrast to RA, mainly reserved for subgroups. It is largely unclear whether long-term spinal progression can be prevented by conventional drug therapy. Treatment with biologics such as anti-TNF-alpha therapy is discussed in Part 2 of this review. To be published in the next issue of the Scandinavian Journal of Rheumatology. Surgical treatment of the spine is indicated in cases of severe instability pain, in cases of deformity endangering the patient in daily life by the limited range of vision, and in patients with neurological deficiency. AS-specific problems are spinal fractures and atlantoaxial instability, which need careful management including surgery. Joint replacement therapy is established and beneficial for AS-disturbed joints of the hip and knee.
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Affiliation(s)
- J Braun
- Rheumazentrum Ruhrgebiet, Herne, Germany.
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Abstract
A great deal of progress has occurred in the past few years in elucidating the causes and designing new treatments for ankylosing spondylitis and other types of spondyloarthritis. In addition to the human leukocyte antigen (HLA)-B27 and other major histocompatibility complex (MHC) genes, chromosomal regions and genes elsewhere in the genome are being implicated both in disease susceptibility and severity. The various ways HLA-B27 may function in causing spondyloarthritis now are better understood to encompass not only antigen presentation but also other mechanisms, possibly all being operative in pathogenesis (misfolding of the HLA-B27 molecule, impaired intracellular killing of bacteria, and HLA-B27 itself serving as an autoantigen). Specific enteric and sexually acquired infections can trigger reactive arthritis, though no specific microbe has been identified in other forms of spondyloarthritis. Intestinal inflammation with impairment of the gut:blood barrier may be operative in driving ankylosing spondylitis and enteropathic arthritis. A number of treatments have been tried in spondyloarthritis, including older agents such as methotrexate and sulfasalazine but also newer drugs such as pamindronate. The recent introduction of tumor necrosis factor (TNF) blockers in the treatment of spondyloarthritis has offered the most hope in not only relieving symptoms and signs of both peripheral arthritis and enthesitis but also spinal disease, which often has been refractory to other agents. Their high cost and considerable side effect profile, however, have necessitated the establishment of guidelines for their use in these diseases in order to target the patient in whom they are likely to have the most benefit.
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Affiliation(s)
- John D Reveille
- Division of Rheumatology, Department of Internal Medicine, The University of Texas-Houston Health Science Center, USA.
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Abstract
Ankylosing spondylitis is the prototype of related diseases commonly called spondylarthropathies which include reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel diseases (enteropathic arthritis) and undifferentiated spondylarthropathies. Ankylosing spondylitis and spondylarthropathies are generally observed in young patients but can be observed later in life or in persons >50 years of age. All the spondylarthropathy subgroups are represented in the elderly with some features particular to this age group. Indeed, radiological aspects of ankylosing spondylitis may be difficult to interpret because of the radiological changes induced by aging. Late-onset peripheral spondylarthropathies are characterised by severe disease, marked elevation of laboratory parameters of inflammation, oligoarthritis involving the lower limbs and oedema of the extremities. Psoriatic arthritis is more severe in the elderly and is associated with worse outcomes than in young patients. The clinical presentation of undifferentiated spondylarthropathy is as varied in the elderly as in young and middle-aged adults. Reactive arthritis and enteropathic arthritis are observed in the elderly more rarely. The effects of aging on drug metabolism and pharmacokinetics, together with the existence of co-morbidities and polypharmacy, are responsible for difficulties in the therapeutic management of late-onset ankylosing spondylitis or spondylarthropathies. Indeed, NSAIDs should be used with caution in older patients because of the high risk of serious gastrointestinal complications. Sulfasalazine and methotrexate have been used as disease-controlling drugs but did not prove very effective. Pamidronate and tumour necrosis factor (TNF)-alpha antagonists offer a therapeutic alternative but have not been specifically tested in the elderly. Pamidronate has been tested in young-onset ankylosing spondylitis and spondylarthropathies with conflicting results but can be used in older patients without risk of major adverse effects. TNFalpha antagonists have been adequately evaluated in ankylosing spondylitis and spondylarthropathies and are associated with dramatic improvement in clinical and biological parameters of disease activity. However, the safety profile of these agents in the elderly is not currently known and careful surveillance, in particular for the risk of infection such as tuberculosis, and/or exacerbation of chronic heart failure, is thus required when using these drugs in this age group.
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Affiliation(s)
- Eric Toussirot
- Department of Rheumatology, University Hospital Jean Minjoz, Besançon, France.
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Rejón E, Giménez MD, Mayordomo L, Rodríguez S, González MP, Marenco JL. Therapeutic efficacy and safety of multiple intravenous infusions of infliximab in refractory ankylosing spondylitis patients with axial involvement. Scand J Rheumatol 2004; 33:323-6. [PMID: 15513681 DOI: 10.1080/03009740310004720] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
OBJECTIVE To evaluate the clinical response and safety profile of infliximab in refractory ankylosing spondylitis patients. METHODS Patients with active ankylosing spondylitis, despite methotrexate therapy, were included in an open-label, single-centre study. Patients were given 3-5 mg/kg infliximab infusions at Weeks 0, 2, 6, and q8 etc up to Week 30, together with methotrexate at the dosage taken prior to study inclusion, and were followed-up for a 34-week period. RESULTS Nine patients with mean age 43 years and mean disease duration 7 years, diagnosed with pure axial ankylosing spondylitis were included. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), duration of morning stiffness, physician's global assessment of disease activity (PhGADA), visual analogue scale (VAS) pain, enthesis index, occiput-to-wall test, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI) significantly improved by Week 6. No adverse events related with the drug were recorded during the 34-week follow-up period. CONCLUSION Efficacy results are similar to those previously published. No adverse events were seen during therapy, and antinuclear antibody profiles were negative. The association of methotrexate with infliximab can improve the safety profile.
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Affiliation(s)
- E Rejón
- Rheumatology Unit, Hospital Valme, Seville, Spain.
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Abstract
Peripheral involvement of the joints, including pauciarticular, asymmetrical, transitory and migrating synovitis and enthesiopathy, is observed in 10-20% of affected inflammatory bowel disease patients. Recurrence is common and frequently coincides with a flare-up of intestinal disease. The true prevalence of axial involvement is less well established. Sacroiliitis is a hallmark of spondylitis, but is under-reported due to its insidious onset and sometimes asymptomatic nature. Radiographic evidence of sacroiliitis is present in about 20-25% of patients. Ankylosing spondylitis, as defined by the Rome criteria, is present in 3-10% of inflammatory bowel disease patients, and is thought to have a different genetic predisposition in these patients compared with 'classic' ankylosing spondylitis: whereas the human leucocyte antigen B27 phenotype is present in 90% of patients with 'classic' ankylosing spondylitis, the prevalence decreases to only 30% in patients with ankylosing spondylitis secondary to Crohn's disease. Polymorphisms involving CARD15 appear to be a possible genetic trigger: 78% of patients with Crohn's disease and symptomatic or asymptomatic sacroiliitis carry at least one mutation, compared with only 48% of control Crohn's disease patients. Moreover, in other forms of spondyloarthropathy, a similar association has been reported: 42% of patients with spondyloarthropathy and associated asymptomatic chronic gut inflammation, who are considered likely to develop Crohn's disease and ankylosing spondylitis, are carriers of at least one CARD15 mutation, compared with only 7% of patients with normal histology. In addition to genetic markers, clinical features support the relationship between gut and joint pathophysiology. In cases of spondyloarthropathy, a very rapid, substantial and sustained improvement in symptoms has been reported following treatment with infliximab, suggesting an essential role for tumour necrosis factor-alpha in spondyloarthropathy, similar to that observed in Crohn's disease.
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Affiliation(s)
- M De Vos
- Department of Gastroenterology, Ghent University Hospital, Belgium.
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Abstract
BACKGROUND Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterized by sacroiliitis and spondylitis. To date, treatment of AS has been limited to the alleviation of symptoms, mainly using non-steroidal anti-inflammatory drugs (NSAIDs). For patients refractory or intolerant to NSAIDs, the disease modifying antirheumatic drugs (DMARDs) have been used as a second line approach. Methotrexate (MTX) is currently one of the most widely used DMARDs and its efficacy in rheumatoid arthritis (RA) has been confirmed (Suarez-Almazor 2003). There is uncertainty whether MTX works in the treatment of AS. OBJECTIVES To evaluate the efficacy and toxicity of methotrexate in the treatment of ankylosing spondylitis. SEARCH STRATEGY Relevant randomised and quasi-randomised trials in any language were sought using the following sources: CENTRAL (Cochrane Central Register of Controlled Trials, Issue 2, 2003), MEDLINE (1966 to June Week 4 2003), EMBASE (1980 to 2003 Week 26), CINAHL (1982 to June Week 3 2003) and the reference section of retrieved articles. SELECTION CRITERIA We evaluated randomised and quasi-randomised trials examining the efficacy of methotrexate on AS. DATA COLLECTION AND ANALYSIS Unblinded trial reports were reviewed independently by two reviewers according to the selection criteria. Disagreements on the inclusion of the studies were resolved, where necessary, by recourse to a third reviewer. The methodological quality of included trials were independently assessed by the same reviewers on randomization, concealment, blindness (participants, care providers and outcome investigators), description of withdrawals and drop-outs and intention-to-treat analysis. The same reviewers independently entered the data extracted from the included trials, using RevMan's double entry facility. In the absence of significant heterogeneity, results were combined using weighted mean difference or standardised mean difference for continuous data, and relative risk for dichotomous data. MAIN RESULTS Two trials met the inclusion criteria. Altan 2001compared naproxen plus MTX (7.5 mg/week orally) with naproxen alone and Roychowdhury 2002 compared MTX (10 mg/week orally) with placebo. The duration of the trials were 12 months and 24 weeks, respectively. They assessed different outcomes except for C-reactive protein (CRP). The included trials treated a total of 81 patients and assessed more than 10 outcomes relevant to the review, covering function, pain, peripheral arthritis/enthesitis, morning stiffness, patient and physician global assessment, CRP and erythrocyte sedimentation rate (ESR). No significant difference between intervention groups was found favouring MTX over no MTX. No serious side effect was reported in either trial. REVIEWERS' CONCLUSIONS There was no statistically significant benefit of MTX in the examined outcomes for AS patients. High quality, larger sample and longer period of randomized controlled trials (possibly with higher dosage of MTX) are needed to verify the uncertainty about the efficacy and toxicity of MTX for the treatment of AS.
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Affiliation(s)
- J Chen
- Australasian Cochrane Centre, Level 1, Block E, Locked Bag 29, Monash Medical Centre, Clayton, Melbourne, Vitoria, Australia, 3168.
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Abstract
Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease responsible for back pain, stiffness and loss of functional capacity. The therapeutic management of AS includes regular physical exercise together with the use of NSAIDs. Second-line treatments, such as sulfasalazine, are required in cases of NSAID-refractory AS. Some patients have severe and inadequately controlled disease, explaining the need for the development of new treatments. This therapeutic development in AS involves the assessment of new NSAIDs, namely COX2 selective agents and new second-line treatments, such as methotrexate (MTX), pamidronate and anti-TNFalpha agents. Controlled studies are lacking for MTX. Pamidronate showed to be effective in NSAID refractory AS patients in open and controlled trials. Anti-TNFalpha agents (infliximab and etanercept) gave promising results with dramatic improvement of AS symptoms in open and preliminary controlled trials, but further studies are required to evaluate the real long-term effects and tolerability of these drugs.
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Affiliation(s)
- Eric Toussirot
- Department of Rheumatology, University Hospital Jean Minjoz, Bd Fleming, F-25030 Besançon, France.
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Abstract
Ankylosing spondylitis (AS) is a complex, potentially debilitating disease that is insidious in onset, progressing to radiological sacroiliitis over several years. Patients with symptomatic AS lose productivity owing to work disability and unemployment, have a substantial use of healthcare resources, and reduced quality of life. The pathogenesis of AS is poorly understood. However, immune mediated mechanisms involving human leucocyte antigen (HLA)-B27, inflammatory cellular infiltrates, cytokines (for example, tumour necrosis factor alpha and interleukin 10), and genetic and environmental factors are thought to have key roles. The detection of sacroiliitis by radiography, magnetic resonance imaging, or computed tomography in the presence of clinical manifestations is diagnostic for AS, although the presence of inflammatory back pain plus at least two other typical features of spondyloarthropathy (for example, enthesitis and uveitis) is highly predictive of early AS. Non-steroidal anti-inflammatory drugs (NSAIDs) effectively relieve inflammatory symptoms and are presently first line drug treatment. However, NSAID treatment has only a symptomatic effect and probably does not alter the disease course. For symptoms refractory to NSAIDs, second line treatments, including corticosteroids and various disease modifying antirheumatic drugs, are employed but are of limited benefit. Emerging biological therapies target the inflammatory processes underlying AS, and thus, may favourably alter the disease process, in addition to providing symptom relief.
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Affiliation(s)
- J Sieper
- Department of Gastroenterology and Rheumatology, UKBF, Free University, Hindenburgdamm 30, 12200 Berlin, Germany.
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