Cardiovascular diseases (CVD) are the leading cause of death worldwide. Therefore, it is essential to understand their relationship and prevalence in different diseases that may present specific risk factors for them. The objective of this document is to analyze the specific prevalence of CVD in patients with inflammatory bowel disease (IBD), describing the presence of classical and non-classical cardiovascular risk factors in these patients. Additionally, we will detail the pathophysiology of atherosclerosis in this patient group and the different methods used to assess cardiovascular risk, including the use of risk calculators in clinical practice and different ways to assess subclinical atherosclerosis and endothelial dysfunction. Furthermore, we will describe the potential influence of medication used for managing patients with IBD on cardiovascular risk, as well as the potential influence of commonly used drugs for managing CVD on the course of IBD. The document provides comments and evidence-based recommendations based on available evidence and expert opinion. An interdisciplinary group of gastroenterologists specialized in IBD management, along with a consulting cardiologist for this type of patients, participated in the development of these recommendations by the Spanish Group of Work on Crohn's Disease and Ulcerative Colitis (GETECCU).

To assess safety of ustekinumab (UST) on treatment of patients with psoriasis and psoriatic arthritis (PsA) by analyze UST related adverse drug events (ADEs).

Data on ADEs associated with UST on psoriasis and PsA were collected from the fourth quarter of 2009 through the third quarter of 2024 in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FEARS) database. A variety of signal quantization techniques such as reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS) are used for analysis.

A total of 67,765 ADE reports with UST on psoriasis and PsA as the primary suspected agent covered 25 system organ classes (SOCs). The three most common ADEs are infections and infestations (n = 9698), general disorders and administration site conditions (n = 6336), and injury, poisoning, and procedural complications (n = 6091). Specifically, reproductive system diseases (n = 262) was identified as unique adverse reactions not mentioned in official drug labels. At the preferred term (PT) level, the most common ADEs were psoriasis exacerbation (n = 3486), lower respiratory tract infection (n = 1302) and latent tuberculosis (n = 121). Strong yet rare signals, including notalgia paraesthetica (n = 3, empirical bayesian geometric mean [EBGM] 154.7) and chronic actinic dermatitis (n = 3, EBGM 101.15), were also detected. Compared to patients with PsA, patients with psoriasis treated with UST exhibit significantly stronger associations with hepatobiliary disorders (n = 955, ROR 2.44, PRR 2.4, information component [IC] 1.26, EBGM 2.4) and neoplasms (n = 3150, ROR 2.61, PRR 2.49, IC 1.31, EBGM 2.49). Spontaneous reports consistently demonstrated higher signal strength for infections and skin disorders compared to healthcare professional (HCP) reports. In contrast, at the PT level, HCP reports tended to emphasize stronger signals for rare or specific conditions.

This study highlights a spectrum of UST-associated ADEs covering 25 SOCs in the treatment of patients with psoriasis and PsA, which emphasizes the need for vigilant clinical monitoring, particularly for infections, hepatobiliary disorders, and rare but high-signal events such as notalgia paraesthetica, chronic actinic dermatitis and pure testicular seminoma stage I. Clinicians should combine insights from both spontaneous and HCP reports and pay special attention to infections and reproductive system disorders.

The relationship between psoriasis, immunomodulatory therapies, and the risk of malignancies is complex and still debated. The scarcity of evidence in this field makes clinicians hesitate to prescribe biological therapies for 'difficult-to-treat' patients.

Based on a comprehensive MEDLINE/PUBMED search of articles published up to November 2024, this review synthesizes the current evidence on the association between psoriasis and cancer. This review specifically addresses four key aspects: the overall cancer risk in psoriatic patients, the potential role of cytokines involved in psoriasis pathogenesis in tumor development, the association between biological therapies and the incidence of new malignancies in this population, and the risk of cancer recurrence or progression in patients with a history of malignancy who are treated with biologics.

Biological therapies do not significantly elevate malignancy risk compared to non-biological treatments or the general population. Evidence is also reassuring for patients with prior malignancy, showing no tumor progression or recurrence. These findings support the timely use of biological treatments in 'difficult-to-treat' patients. Regular cancer screenings and risk-factor minimization should always be recommended for psoriatic patients undergoing immunomodulatory therapies. Multidisciplinary management involving oncologists is suggested, particularly for patients with active and advanced oncological disease.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. The safety and efficacy of deucravacitinib in psoriasis has been demonstrated through 3 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials enrolling adults with moderate to severe plaque psoriasis.

To review the effect of deucravacitinib treatment on adverse events of interest (AEIs) over 3 years in POETYK PSO-1, PSO-2, and LTE, cumulative exposure-adjusted incidence rates (EAIRs) of AEIs were recorded through 3 years.

AEIs and 3-year EAIRs of select infections included serious infections (2.5/100 person-years [PY]), COVID-19 (1.6/100 PY), and herpes zoster (0.6/100 PY). Excluding COVID-19, the serious infections EAIR was 0.9/100 PY. Major adverse cardiovascular event (MACE) and venous thromboembolism EAIRs were 0.3/100 PY and 0.1/100 PY, respectively. The EAIRs for malignancies were 0.9/100 PY overall and 0.5/100 PY, excluding nonmelanoma skin cancer (NMSC). Cutaneous events included acne (EAIR, 1.3/100 PY) and folliculitis (EAIR, 1.1/100 PY). Three-year cumulative EAIRs generally remained stable or decreased relative to 1-year rates. EAIRs of non-COVID-19 serious infections, malignancies excluding NMSC, and MACE through 3 years were consistent with rates for other antipsoriatic agents from clinical trials, disease registries, and real-world claims data.

In adults with plaque psoriasis treated with deucravacitinib, the cumulative incidence of AEIs remained comparable or decreased over 3 years of follow-up and aligned with comparison data for other antipsoriatic therapies.

Safe and effective long-term treatments for moderate to severe plaque psoriasis are needed.

To evaluate the long-term safety and efficacy of deucravacitinib through 3 years (week 148) in the randomized POETYK PSO-1, PSO-2, and nonrandomized long-term extension (LTE) trials.

PSO-1/PSO-2 were global, 52-week, randomized, double-blinded phase 3 trials in patients with moderate to severe plaque psoriasis. After completing 52 weeks of treatment in PSO-1/PSO-2, patients could enroll in the prespecified, ongoing, nonrandomized LTE trial. The peak of the global COVID-19 pandemic coincided with the LTE trial. Patient enrollment in the LTE started August 12, 2019; safety and efficacy were assessed through June 15, 2022; and these data were analyzed through June 28, 2024.

The PSO-1/PSO-2 trials randomized patients 1:2:1 to oral placebo, deucravacitinib, 6 mg once daily, or apremilast, 30 mg twice daily. Patients enrolling in the LTE trial received open-label deucravacitinib, 6 mg once daily.

Safety outcomes were evaluated in patients who received 1 or more doses of deucravacitinib. Efficacy outcomes included 75% or greater or 90% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician Global Assessment scores of 0 (clear) or 1 (almost clear) (sPGA 0/1) and were assessed in patients who received deucravacitinib treatment from day 1 of the parent trials who continued in the LTE trial.

Of 1519 patients who received 1 or more doses of deucravacitinib, 513 received continuous deucravacitinib treatment from day 1 and entered the LTE trial. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were decreased or similar in the 1-year vs 3-year cumulative periods, respectively, for adverse events (AEs) (229.2 vs 144.8; 95% CI, 215.4-243.9 vs 137.1-153.0), serious AEs (5.7 vs 5.5; 95% CI, 4.4-7.4 vs 4.7-6.4), discontinuations due to AEs (4.4 vs 2.4; 95% CI, 3.3-5.9 vs 2.0-3.0), and deaths (0.2 vs 0.3; 95% CI, 0.1-0.8 vs 0.2-0.6). Incidence rates of the most common AEs (EAIR per 100 person-years ≥5) during the 1-year and 3-year cumulative periods, respectively, were nasopharyngitis (26.1 vs 11.4; 95% CI, 23.0-29.8 vs 10.2-12.7), COVID-19 (0.5 vs 8.0; 95% CI, 0.2-1.2 vs 7.1-9.1), and upper respiratory tract infection (13.4 vs 6.2; 95% CI, 11.3-16.0 vs 5.4-7.2). EAIRs for AEs of interest, including herpes zoster, major adverse cardiovascular events, and malignant diseases, remained low and were decreased or comparable between the 1-year and 3-year cumulative periods. Clinical response rates were maintained through 3 years.

The findings of this integrated analysis of the phase 3 POETYK PSO-1, PSO-2, and nonrandomized LTE trials demonstrate a consistent safety profile and durable clinical response of continuous treatment with deucravacitinib through 3 years of treatment in patients with psoriasis.

ClinicalTrials.gov Identifiers: NCT03624127, NCT03611751, and NCT04036435.

The association between psoriasis and increased cancer risk is gaining recognition as studies reveal shared inflammatory and immune pathways. This review examines the relationship between psoriasis and neoplasia, focusing on cancer risk factors in psoriasis patients, the biological pathways underlying this connection, and the impact of various psoriasis treatments on cancer development. Psoriasis patients have a heightened incidence of certain cancers, such as lymphomas, skin cancers, and urological malignancies, potentially linked to immune dysregulation and chronic inflammation. Immunomodulatory treatments for psoriasis, including conventional systemic therapies and biologics, present varied cancer risks, with others, such as phototherapy, associated with an elevated risk of skin cancers. For oncologic patients with psoriasis, management necessitates a tailored approach, balancing effective psoriasis control with minimizing cancer progression risks. The emergence of IL-17 inhibitors, IL-23 inhibitors, and small-molecule therapies offers promising therapeutic alternatives with favorable safety profiles for these patients. This review underscores the need for interdisciplinary collaboration to optimize care for patients managing both psoriasis and malignancy.

Psoriasis (PsO), a chronic inflammatory skin disorder affecting a substantial proportion of populations globally, often necessitates systemic treatment including biologics. This 14-year cohort study, based on Danish national register data, aimed to investigate the enduring safety profile of ustekinumab compared to other systemic psoriasis treatments.

Using comprehensive Danish national register data, this study scrutinized patients diagnosed with psoriasis or psoriatic arthritis (PsA) who received ustekinumab. The treatment group comparators were non-biological systemic treatment (non-biologic), tumor necrosis factor α inhibitor medicine groups (TNF-α), interleukin (IL)-17 inhibitors (IL-17), and IL-23 inhibitors (IL-23). The study periods for comparisons were 2009-2022 for non-biologic and TNF-α, 2015-2022 for IL-17, and 2018-2022 for IL-23. Outcomes were malignancies, cardiovascular events, serious infections, and serious hypersensitivity reactions. Cox proportional hazards regression models were employed to analyze two estimands: a standard intention-to-treat (ITT) estimand and a continuous-index-treatment (CIT) estimand, which considered switch and re-initiation of treatments within individuals.

Users of ustekinumab were found to be younger on average, with an average age of 45.1 years compared to 51.6, 47.2, 49.0, and 48.4 years in the non-biologic, TNF-α, IL-17, and IL-23 groups, respectively. Also, 57.3% of the ustekinumab users were male, compared to 46.7%, 48.9%, 50.9%, and 58.3% for the non-biologic, TNF-α, IL-17, and IL-23 groups, respectively. Although the hazard ratio estimates varied across comparators, ustekinumab was found to be safe: regardless of PsA status, no discernible safety signals in terms of malignancy, MACE, severe infections, or severe hypersensitivity reactions were observed for ustekinumab when compared to the treatment comparators.

The present study corroborated the enduring safety of ustekinumab in the context of PsO treatment.

Biologicals targeting interleukin (IL)-17 and IL-23 improve quality of life in psoriasis and other chronic autoimmune disorders with a favorable safety profile. However, current guidelines do not recommend their use in patients with recent oncologic history due to limited evidence.

To understand the impact of IL-17 and IL-23 inhibitors on cancer development, progression, and recurrence by systematically reviewing available literature.

We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Most studies investigating the use of IL-23 and IL-17 blockers did not find a higher incidence of cancer compared to the general population. One study observed no relapse in patients with a history of cancer.

The systematic review is limited due to variations in study designs and outcomes, making it difficult to achieve a comprehensive synthesis and comparison between studies. Furthermore, small sample sizes were notable.

Preclinical studies suggest that treating psoriasis with IL-17 or IL-23 blockers is safe, also in patients witch active cancer or a history of it. Pharmacovigilance data show no increased malignancy rate in patients treated with these treatment modalities. However, data on relapse in patients with a history or active malignancy are limited.

Several studies have described increased risk ratios of certain types of malignancies in patients with severe psoriasis. Among these, the lymphoproliferative disorders, including non-Hodgkin's lymphoma, cutaneous T-cell lymphoma and non-melanoma skin cancer, have been described most frequently. In addition to traditional cancer risk factors, some psoriasis treatments may also be implicated as potential carcinogens. The aim of this study was to perform a review of current literature on the association between psoriasis, the therapies against this disease and skin cancer, focusing on both epidemiology and the potential mechanism involved. Some psoriasis treatments, such as psoralen and ultraviolet A (PUVA) therapy and cyclosporine, have been associated with increased risk of skin cancer. Variable data have been reported for anti-tumour necrosis factor (TNF) drugs, whereas other class of biologics, like anti-IL17 and IL23, as well as ustekinumab, seem not to be related to skin cancer risk, such as the case of currently available small molecules.

Psoriasis is a chronic, immune-mediated, inflammatory skin disease, associated with multiple comorbidities and psychological and psychiatric disorders. The quality of life of patients with this disease is severely compromised, especially in moderate-to-severe plaque psoriasis. Secukinumab, a fully humanized monoclonal antibody, was the first anti-interleukin (IL)-17 biologic approved for treating psoriasis. Secukinumab demonstrated long-lasting efficacy and a good safety profile in individuals with plaque psoriasis, and it is associated with an improvement in health-related quality of life. While there is evidence that early treatment with systemic therapy can affect disease progression and improve long-term outcomes in other autoimmune diseases, evidence is limited in psoriasis, especially in real-world settings. This review provides an overview of studies describing the effectiveness of secukinumab in the treatment of psoriasis summarizing the literature and focusing on real-world evidence and early intervention.

In this debate at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, arguments were made contrasting the first-line use of oral targeted small-molecule drugs vs biologic therapy for the treatment of moderate-to-severe psoriasis (PsO) after failure of conventional therapy. Arguments in favor of small-molecule drugs included good efficacy and safety, patient preference, cost savings, global health equity, and environmental stewardship. Arguments in favor of biologics included superior efficacy, excellent safety, availability of long-term data, pediatric regulatory approvals, and potential benefit for comorbidities. By the end of the debate, there was recognition of significant pros and cons of each approach. Both small-molecule drugs and biologic therapy are valuable options for PsO treatment, and their use can be tailored toward specific individuals or healthcare systems.

Biologic therapies targeting tumor necrosis factor alpha (TNF-α) (infliximab, adalimumab, certolizumab, etanercept), the p40 subunit shared by IL-12 and IL-23 (ustekinumab), the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab), IL-17A (secukinumab, ixekizumab), IL-17-RA (brodalumab) and both IL-17A and IL-17F (bimekizumab) have revolutionized the treatment of psoriasis. In both the short and long term, risankizumab had highest Psoriasis Area and Severity Index 90 scores compared to other oral and injectable biologics. IL-23 inhibitors had lowest rates of short-term and long-term adverse events and most favorable long-term risk-benefit profile compared to IL-17, IL-12/23, and TNF-α inhibitors.

Crohn's disease and ulcerative colitis are lifelong chronic inflammatory conditions, with many patients requiring ongoing immunomodulatory drug therapy for maintenance treatment. Recent therapeutic goals in inflammatory bowel disease (IBD) are not only aimed at symptomatic remission but also at achieving mucosal healing to improve the natural course of the disease. In this context, therapeutic approaches are being applied in clinical settings that involve early and appropriate use of drugs, such as immunomodulators or biologics, that have the potential to induce healing of the inflamed intestine before irreversible intestinal damage occurs. All drugs that continuously control intestinal inflammation in IBD can heal the mucosa and potentially reduce the incidence of colitis-associated bowel cancer; however, the continuous use of immunosuppressants can potentially increase the risk of malignancies. The safety issues of the drugs used in clinical practice are partly confirmed during their development processes or shortly after initial marketing, but in other cases, they are estimated through post-marketing case reports or epidemiological studies, sometimes decades after drug approval. This review explores the risks associated with malignancies related to the treatment of IBD, focusing on drugs currently approved in Republic of Korea.

This study observed the effectiveness of ustekinumab and reactivation risk of concurrent latent tuberculosis infection (LTBI) and inactive hepatitis B virus (HBV) infection in Chinese mainland psoriasis patients on ustekinumab treatment.

This retrospective, multicenter, observational study was conducted in three centers in China. Adult patients with moderate to severe plaque psoriasis were treated with ustekinumab for 28 weeks. The effectiveness endpoint included 75% and 90% improvement in Psoriasis Area Severity Index (PASI75/90) response rate, percentage of PASI improvement, change of absolute PASI score and body surface area involvement (BSA) score, absolute PASI ≤1/3 and Physicians' Global Assessment (PGA)=0/1, as well as Dermatology life quality index (DLQI)=0/1 response rate at week 4, 16 and 28. Screening of tuberculosis and hepatitis were performed at baseline and week 28.

A total of 82 patients were enrolled between March 2021 and May 2023 and the number of patients combined with LTBI and inactive HBV infection was 20 and 21 respectively. The PASI75 and PASI90 response rate at week 28 was 95.1% and 81.7% respectively. The mean PASI score decreased from 14.93 ± 12.07 at baseline to 0.78 ± 1.86 at week 28, and the mean BSA score decreased from 21% ± 18% at baseline to 1% ± 2% at week 28 (both P<0.001 compared with baseline). DLQI 0/1 response rate at week 28 was 73.2%. No reactivation of LTBI and inactive HBV infection and also no new-onset tuberculosis and hepatitis B occurred in patients without LTBI and inactive HBV infection at baseline.

Ustekinumab demonstrated great effectiveness in Chinese plaque psoriasis patients and good safety in psoriasis concurrent with LTBI and inactive HBV infection under the real-world setting.

The management of patients affected by moderate-to-severe psoriasis may be challenging, in particular in patients with serious infectious diseases [tuberculosis (TB), hepatitis B and C, HIV, COVID-19]. Indeed, these infections should be ruled out before starting and during systemic treatment for psoriasis. Currently, four conventional systemic drugs (methotrexate, dimethyl fumarate, acitretin, cyclosporine), four classes of biologics (anti-tumour necrosis factor alpha, anti-interleukin (IL)12/23, anti-IL-17s, and anti-IL-23], and two oral small molecules (apremilast, deucravacitinib) have been licensed for the treatment of moderate-to-severe psoriasis. Each of these drugs is characterized by a unique safety profile which should be considered before starting therapy. Indeed, some comorbidities or risk factors may limit their use. In this context, the aim of this manuscript was to evaluate the management of patients affected by moderate-to-severe psoriasis with serious infectious diseases.

Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. In addition, there may be a link between the use of thiopurines or anti-tumor necrosis factor drugs (anti-TNF) and these pathologies. The treatment of patients with Crohn's disease who have previously been diagnosed with lymphoma is a challenge for gastroenterologists. In this report, we examine important clinical issues related to the treatment of patients with inflammatory bowel disease with active lymphoma, as well as of patients with hematological cancer history. In this discussion, we take into account most of the available treatments for inflammatory bowel disease, as well as the impact of chronic inflammation and viral infections. In addition, we try to find common ground for the development of lymphoproliferative disorders and autoimmune diseases. Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. Chronic inflammatory processes and viral infections play an important role in carcinogenesis. In addition, there may be a link between the use of thiopurines or anti-TNF drugs and these pathologies. A significant risk of the development of lymphoma in people undergoing each therapy should be considered, and it should be estimated how much greater this risk will be in patients with a history of lymphoproliferative disorders. The following review is an attempt to answer which therapy would be the most appropriate for patients with Crohn's disease and a history of lymphoma treatment. A lack of clear guidelines creates great challenges for doctors.

Ustekinumab use in ulcerative colitis had shown low adverse event and high persistence rates to 3 years via the UNIFI long-term extension study. Outcomes beyond 3 years have not been previously described. We describe the safety signals of the entire UNIFI Australian population beyond 3 years.

This retrospective multicenter observational cohort study recruited from all Australian UNIFI centers. The primary outcome was safety via adverse events. Secondary outcomes included the clinical relapse rate on ustekinumab, and the need to switch from ustekinumab to an alternate agent.

There were 14 patients [11 male, mean age 47 (±14) years], with a median diagnosis of 10.8 (±4.5) years prior to UNIFI enrollment. Median follow-up was 298 weeks (5.7 years) (Interquartile range (IQR): 220-311 weeks). Within the long-term extension, there were three serious adverse events and one minor event. 42.9% (6/14) patients had clinical relapses, of which clinical remission was recaptured in 83.3% (5/6). 85.7% (12/14) persisted on ustekinumab in the long-term, with 7.1% (1/14) electively ceasing ustekinumab and 7.1% (1/14) changed from ustekinumab due to clinical relapse.

For moderate-to-severe UC in Australia, ustekinumab maintained efficacy beyond 3 years with a high persistence rate and no new safety signals.

The trial is registered at ANZCTR (identifier: ACTRN12622001332718).

Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.

Ustekinumab (UST), a human monoclonal antibody that binds the p40 subunit of interleukin 12 (IL-12) and IL-23, is licensed for induction and maintenance therapy of moderate to severe inflammatory bowel disease (IBD). To date, there is limited data published on any potential association between ustekinumab serum trough levels and mucosal healing in order to guide treatment strategies and appropriate dosing.

This study aims to identify a relationship between maintenance ustekinumab serum trough levels and mucosal healing and/or response in patients with Crohn's disease in an observational cohort study.

Ustekinumab serum trough levels and antibody titres were analyzed in patients on maintenance drug using an ELISA drug-tolerant assay. Mucosal response (MR) was defined as ≥50% reduction in fecal calprotectin level (FC) and/or ≥50% reduction in the Simple Endoscopic Score for Crohn's Disease (SES-CD score). Mucosal healing (MH) was defined as FC ≤150 µg/mL and/or global SES-CD score ≤5. Median trough levels were analyzed using the Kruskal-Wallis test, and logistic regression was used to determine sensitivity and specificity of levels predicting mucosal response.

Forty-seven patients on maintenance ustekinumab for Crohn's disease were included in this study. The majority were female (66%), with a median age of 40 years (21-78 years). The majority of patients were biologic-experienced (89.4%, n = 42). Patients with histologically confirmed Crohn's disease represented 100% (n = 47) of the cohort. Over one-third of patients (n = 18, 38.3%) were on higher than standard dosing of 90 mg every 8 weeks. Patients with mucosal healing (n = 30) had significantly higher mean serum ustekinumab levels (5.7 µg/mL, SD 6.4) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). A serum ustekinumab trough level greater than 2.3 µg/mL was associated with MH, with a sensitivity of 100% and specificity of 90.6% (likelihood ratio 10.7). Similarly, for patients with MR (n = 40), we observed a higher mean serum ustekinumab trough level (5.1 µg/mL, SD 6.1) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). Furthermore, a serum ustekinumab trough level greater than 2.3 µg/mL was associated with a 10-fold increased likelihood of mucosal response vs mucosal nonresponse (sensitivity 100%, specificity 90.5%, likelihood ratio 10.5).

This study demonstrates that higher ustekinumab serum trough levels are associated with a greater likelihood of achieving mucosal healing and mucosal response in patients with Crohn's disease regardless of prior biologic exposure. Further prospective studies are required to correlate target maintenance trough levels and the optimal time to dose-escalate in order to improve patient outcomes.

There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer biologic and small-molecule treatments.

We performed a systematic search of PubMed and Embase databases to identify studies examining the impact of immunosuppressive therapies on cancer recurrence across several immune-mediated diseases. Studies were pooled together using random-effects meta-analysis and stratified by type of treatment. Primary outcome was occurrence of incident cancers, defined as new or recurrent.

Our meta-analysis included 31 studies (17 inflammatory bowel disease, 14 rheumatoid arthritis, 2 psoriasis, and 1 ankylosing spondylitis) contributing 24,328 persons and 85,784 person-years (p-y) of follow-up evaluation. Rates of cancer recurrence were similar among individuals not on immunosuppression (IS) (1627 incident cancers, 43,765 p-y; 35 per 1000 p-y; 95% CI, 27-43), receiving an anti-tumor necrosis factor (571 incident cancers, 17,772 p-y; 32 per 1000 p-y; 95% CI, 25-38), immunomodulators (1104 incident cancers, 17,018 p-y; 46 per 1000 p-y; 95% CI, 31-61), combination immunosuppression (179 incident cancers, 2659 p-y; 56 per 1000 p-y; 95% CI, 31-81). Patients receiving ustekinumab (5 incident cancers, 213 p-y; 21 per 1000 p-y; 95% CI, 0-44) and vedolizumab (37 incident cancers, 1951 p-y; 16 per 1000 p-y; 95% CI, 5-26) had numerically lower rates of cancer. There were no studies on Janus kinase inhibitors. Stratification of studies by timing of immunosuppression initiation did not reveal a medication effect based on early (<5 years) or delayed treatment initiation.

In patients with immune-mediated diseases and a history of malignancy, we observed similar rates of cancer recurrence in those on no immunosuppression compared with different immunosuppressive treatments.

There have been several reports of dupilumab use and the development of CTCL; however, the risk of CTCL development has not been adequately evaluated at the population level. The objective of this study is to determine whether dupilumab administration for AD is associated with an increased risk of developing CTCL and to identify at-risk populations within this group. This retrospective cohort study used TriNetX, a deidentified medical record database including over 107 million patients, to identify eligible patients. Treatment and control groups were evaluated for the development of CTCL. Patients of any age with a documented diagnosis of AD were included. The treatment cohort included individuals treated with dupilumab, while the control cohort included AD patients treated with alternative therapies. Selected biologics were excluded from both groups. Subgroup analyses were performed to evaluate three age groups and to identify whether the risk of CTCL development was higher within a given time frame after starting dupilumab. We identified a total of 1,181,533 patients with AD. Of these, 19,612 patients were prescribed dupilumab. Both treatment and control groups included 19,612 patients matched for age, race, and sex. The mean age was 32.3 years (P = 0.96), and females accounted for approximately 52% (P = 0.93) in both groups. Patients treated with dupilumab for AD had an increased relative risk (RR) of developing CTCL compared to those never treated with dupilumab (RR = 4.59, 95% confidence interval 2.459-8.567, P < 0.0001). Subgroup analysis revealed that about half of the CTCL cases after dupilumab therapy (54.5%, 30/55) occurred in patients over the age of 60 years. In contrast, all CTCL cases (100%, 12/12) within the untreated cohort were observed in individuals over the age of 60. Of the patients diagnosed with CTCL following dupilumab use, the majority (62%, 34/55) were diagnosed within the first year. Overall, we find that the use of dupilumab for treating AD is associated with an increased relative risk of developing CTCL. This risk is highest in the first year of therapy and in adult patients. These findings suggest exercising caution in treating select groups of patients with dupilumab.

CT-P43 is a candidate ustekinumab biosimilar in clinical development.

This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis.

This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here.

In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI -0.23, 4.32) and 0.94 (95% CI -2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43.

CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles.

ClinicalTrials.gov Identifier: NCT04673786; date of registration: 17 December, 2020.

To assess cancer risks in patients with psoriasis and the effect of TNF-α inhibitor and interleukin (IL)-12/23 inhibitor therapy on those cancer risks.

Using the Korean Health Insurance Review and Assessment Service database, patients with newly diagnosed psoriasis between 2008 to 2019 were included. Standardized incidence ratios (SIRs) of overall and specific cancers were calculated in patients with psoriasis. The effect of TNF-α inhibitor and IL-12/23 inhibitor exposure on the risk of cancers was assessed by multivariable Cox regression models.

In total, 191,678 patients with psoriasis were included in this study. The overall risk of cancer was significantly higher in patients with psoriasis than in the general population (SIR, 1.12; 95% confidence interval (CI), 1.09-1.14). TNF-α inhibitor users had a significantly higher risk for overall cancer (adjusted hazard ratio (aHR), 1.41; 95% CI 1.01-1.97). In contrast, IL-12/23 inhibitor exposure had a significantly lower risk for overall cancer (aHR, 0.57; 95% CI 0.37-0.87). Among specific cancers, the risks of non-Hodgkin lymphoma (aHR, 2.98; 95% CI 1.02-8.69) were increased by TNF-α inhibitor therapy, while the risk of other cancers, including nonmelanoma skin cancer (aHR, 2.31; 95% CI 0.51-10.46), was not significantly altered by TNF-α inhibitor therapy.

TNF-α inhibitor therapy in psoriasis is associated with a significantly increased risk of overall cancer and lymphoma, while the risk of solid organ cancer was not affected by this therapy. The IL-12/23 inhibitor is not associated with an increased risk of any cancer.

Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.

To compare the benefits and harms of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their benefits and harms.

For this update of the living systematic review, we updated our searches of the following databases monthly to October 2022: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase.

Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation).

We conducted duplicate study selection, data extraction, risk of bias assessment, and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety).

This update includes an additional 12 studies, taking the total number of included studies to 179, and randomised participants to 62,339, 67.1% men, mainly recruited from hospitals. Average age was 44.6 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (56%). We assessed a total of 20 treatments. Most (152) trials were multicentric (two to 231 centres). One-third of the studies (65/179) had high risk of bias, 24 unclear risk, and most (90) low risk. Most studies (138/179) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 49.16, 95% CI 20.49 to 117.95), bimekizumab (RR 27.86, 95% CI 23.56 to 32.94), ixekizumab (RR 27.35, 95% CI 23.15 to 32.29), risankizumab (RR 26.16, 95% CI 22.03 to 31.07). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab and ixekizumab were significantly more likely to reach PASI 90 than secukinumab. Bimekizumab, ixekizumab, and risankizumab were significantly more likely to reach PASI 90 than brodalumab and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab, and brodalumab), and anti-IL23 drugs except tildrakizumab were significantly more likely to reach PASI 90 than ustekinumab, three anti-TNF alpha agents, and deucravacitinib. Ustekinumab was superior to certolizumab. Adalimumab, tildrakizumab, and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with very low- to moderate-certainty evidence for all the comparisons. The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.

Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.6 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was very low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Psoriasis is a chronic, inflammatory, non-communicable skin disorder that affects a patient's social and emotional well-being. It is characterized by hyperproliferation of keratinocytes, irregular shedding of skin cells, and abnormal invasion of inflammatory mediators. The treatment strategy is designed based on the severity of the disease condition starting from topical, phototherapy, systemic, and biologics. In recent years, extensive research into the underlying mechanisms of psoriasis has led to significant advancement in treatment options from small molecules to biologics.

This review focuses on intracellular and molecular mechanisms such as AhR, A3AR, RIP1, CGRP, and S1P that serve as novel pharmacological targets for psoriasis. Moreover, new molecules are approved or are under clinical investigation to interfere with these target mechanisms.

A detailed understanding of signaling pathways provides potential targets and molecular mechanisms for the inflammatory cascade in psoriasis. This has led to the development of small molecules targeting specific pathways. Further, the combination of nanotechnology can assist in dose reduction leading to reduced adverse effects in the management of psoriasis.

Limited data exist on skin cancer risk in patients with psoriasis using biologics. Here, we report treatment-emergent adverse events (TEAEs) of skin cancer in patients treated with ixekizumab from psoriasis clinical trials.

Integrated safety databases from 17 clinical trials of adults with moderate-to-severe psoriasis treated with ≥ 1 dose of ixekizumab for ≤ 5 years were used to analyze exposure-adjusted incidence rates (IRs) per 100 patient-years of exposure (PYE) and clinically characterize dermatologist-adjudicated skin cancer TEAEs.

Of 6892 patients, 58 presented with ≥ 1 skin cancer TEAE (IR 0.3) with IRs remaining stable with longer ixekizumab exposure. Non-melanoma skin cancer (NMSC) was the most common event (IR 0.3) affecting 55 patients; of those, 44 had basal cell carcinoma (IR 0.2) and 16 had squamous cell carcinoma (IR 0.1). Two treatment-emergent melanoma events were identified; neither were classified as serious AEs.

Incidence of skin neoplasms in patients with psoriasis treated with ixekizumab for ≤ 5 years was low, and among those events, NMSC was most common. Limitations included that longer exposure may be required to confirm risk of skin cancer and that the study exclusion criteria of several studies, which excluded patients with skin cancer events within 5 years prior to baseline, might limit interpretation of skin cancer risk in this cohort. These findings support the safety profile of ixekizumab for patients requiring long-term psoriasis control.

Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, comprises multiple complex immune-mediated disorders. Early diagnosis and prompt disease control may prevent long-term complications and hospitalization. The therapeutic options have expanded in the last two decades, with the development of biologics and small molecules targeting specific pathways implicated in inflammatory bowel disease pathogenesis. The interleukin (IL)-23/Th-17 axis is one such example. Targeting IL-12/23 is effective for the treatment of both moderate-to-severe Crohn's disease and ulcerative colitis, and ustekinumab (an IL-12/23p40 antagonist) is approved for both indications. In patients with psoriasis, improved clinical outcomes were observed with agents that more selectively targeted IL-23 (IL-23p19 antagonists) compared with those that target both IL-12 and IL-23. Many specific IL-23p19 antagonists are currently being investigated in Crohn's disease and ulcerative colitis, and risankizumab has been recently approved for moderate-to-severely active Crohn's disease. In this review, we summarize the mechanisms of action and the evidence from clinical trials supporting the efficacy and safety of IL-23p19 antagonists for the treatment of inflammatory bowel disease.

Psoriasis is a common chronic, immune-mediated, inflammatory disease with associated comorbidities. Common psoriasis-associated comorbidities include psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory digestive syndromes, and depression. A less studied association is between psoriasis and specific-site cancers. A key cell in the pathophysiology of psoriasis is the myeloid dendritic cell, which links the innate and adaptive immune systems, and therefore is involved in the control of cancer-prevention mechanisms. The relationship between cancer and inflammation is not new, with inflammation being recognized as a key element in the development of neoplastic foci. Infection leads to the development of local chronic inflammation, which further leads to the accumulation of inflammatory cells. Various phagocytes produce reactive oxygen species that cause mutations in cellular DNA and lead to the perpetuation of cells with altered genomes. Therefore, in inflammatory sites, there will be a multiplication of cells with damaged DNA, leading to tumor cells. Over the years, scientists have tried to assess the extent to which psoriasis can increase the risk of developing skin cancer. Our aim is to review the available data and present some information that might help both the patients and the care providers in properly managing psoriatic patients to prevent skin cancer development.

Patients with treated solid tumours (TSTs) are a highly heterogeneous population at an increased risk for malignancy compared with the general population. When treating psoriasis in patients with a history of TSTs, clinicians are concerned about the immunosuppressive nature of psoriasis therapies, the possibility of augmenting cancer recurrence/progression, and infectious complications. No direct, high-level evidence exists to address these concerns.

We aim to provide a structured framework supporting healthcare professional and patient discussions on the risks and benefits of systemic psoriasis therapy in patients with previously TSTs. Our goal was to address the clinically important question, "In patients with TSTs, does therapy with systemic agents used for psoriasis increase the risk of malignancy or malignancy recurrence?"

We implemented an inference-based approach relying on indirect evidence when direct clinical trial and real-world data were absent. We reviewed indirect evidence supporting inferences on the status of immune function in patients with TSTs. Recommendations on systemic psoriasis therapies in patients with TSTs were derived using an inferential heuristic.

We identified five indirect indicators of iatrogenic immunosuppression informed by largely independent bodies of evidence: (1) overall survival, (2) rate of malignancies with psoriasis and systemic psoriasis therapies, (3) rate of infections with psoriasis and systemic psoriasis therapies, (4) common disease biochemical pathways for solid tumours and systemic psoriasis therapies, and (5) solid organ transplant outcomes. On the basis of review of the totality of this data, we provided inference-based conclusions and ascribed level of support for each statement.

Prior to considering new therapies for psoriasis, an understanding of cancer prognosis should be addressed. Patients with TSTs and a good cancer prognosis will have similar outcomes to non-TST patients when treated with systemic psoriasis therapies. For patients with TSTs and a poor cancer prognosis, the quality-of-life benefits of treating psoriasis may outweigh the theoretical risks.

Cutaneous T-cell lymphoma following biologic therapy is extremely rare.

The aim of this systematic review was to investigate the development of cutaneous T-cell lymphoma (CTCL) following treatment with a biologic agent.

A systematic literature review was performed for patients who developed CTCL after exposure to biologic therapy. Works were limited to English language and excluded animal studies, guidelines, and protocols. Potentially eligible titles were identified using controlled vocabulary in tandem with key words. The search strategy was peer-reviewed prior to execution.

Twenty-eight total studies revealed sixty-two patients who developed CTCL following exposure to a biologic agent. Of these, 44% were Caucasian, and the median age at diagnosis was 56 years. Seventy-six percent of patients received biologic therapy for a primary inflammatory skin condition. Dupilumab was the most reported (42%) agent amongst the cohort. The median time from initiation of the biologic agent to diagnosis of CTCL in these cases was 4 months (range: 0-84). Mycosis fungoides (65%) and Sézary syndrome (10%) were the most common subtypes of CTCL diagnosed. Twenty-one (34%) patients were reported to be alive with disease, outcome was not reported in 21 patients (34%), ten patients (16%) were alive and in complete remission, eight patients (13%) died of disease and two patients (3%) died due to other causes.

While biologic agents may have a role in the development of CTCL, in order to definitively elucidate their role, more methodologically robust studies (such as those that utilize population databases) would need to occur.

This is the English version of Japanese guidance for use of biologics for psoriasis (the 2022 version). As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti-tumor necrosis factor-α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti-interleukin (IL)-12/IL-23p40 antibody, which was launched in Japan in 2011. Moreover, after 2015, three IL-17 inhibitors, the IL-17A antibody preparations secukinumab and ixekizumab, and an anti-IL-17 receptor antibody preparation brodalumab were marketed. Furthermore, after 2018, the anti-IL23p19 antibody preparations guselkumab and risankizumab, the TNF inhibitor certolizumab pegol, the IL-23 inhibitor tildrakizumab, and the anti-IL-17A/F antibody bimekizumab were marketed. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors, and patient background factors, sharing such information with patients. The followings can be listed as points to be considered for the selection of biologics: drug effects (e.g., strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g., infections, administration-related reactions, and relationships with other comorbidities), convenience for patients (e.g., hospital visit intervals, self-injection, maintenance therapy at clinics, feasibility of drug discontinuation/re-administration), and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above-mentioned factors.

Psoriasis is a systemic immune-mediated disease associated with an increased risk of comorbidities, such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory bowel disease, psychiatric disorders, and malignancy. In recent years, with the advent of biological agents, the efficacy and safety of psoriasis treatments have dramatically improved. Presently, tumor necrosis factor-α inhibitors, interleukin-17 inhibitors, interleukin-12/23 inhibitors, and interleukin-23 inhibitors are approved to treat moderate-to-severe psoriasis. Small-molecule inhibitors, such as apremilast and deucravacitinib, are also approved for the treatment of psoriasis. Although it is still unclear, systemic agents used to treat psoriasis also have a significant impact on its comorbidities by altering the systemic inflammatory state. Data from clinical trials and studies on the safety and efficacy of biologics and small-molecule inhibitors provide important information for the personalized care and treatment for patients with psoriasis. Notably, treatment with interleukin-17 inhibitors is associated with new-onset or exacerbations of inflammatory bowel disease. In addition, great caution needs to be taken when using tumor necrosis factor-α inhibitors in patients with psoriasis with concomitant congestive heart failure, multiple sclerosis, and malignancy. Apremilast may induce weight loss as an adverse effect, presenting also with some beneficial metabolic actions. A better understanding of the characteristics of biologics and small-molecule inhibitors in the treatment of psoriasis comorbidities can provide more definitive guidance for patients with distinct comorbidities.

Psoriatic arthritis (PsA) is a chronic arthritis typically associated with cutaneous psoriasis (PsO). Its pathogenesis is connected to an innate and acquired immune response, as well as genetic risk alleles. The extent of immunopathogenic mechanisms and the heterogenicity of clinical manifestation make the identification of patient-targeted therapies a critical issue, and the treatment decision challenging in patients' management.

This review includes a brief overview of biological and small-molecule therapies, focusing on evidence from clinical trials and real-world data that support their use in PsA. We summarize novel and future possible therapeutic strategies, the importance that comorbidities have on selection of therapy and discuss the adverse event of each drug. Relevant papers for up to 1 August 2022 (trials, real-life studies, and reviews) regarding biologics and/or small molecules were summarized.

In recent years, the treatment of PsA has been revolutionized by new targeted therapies, which offer the opportunity to perform a tailored-tail management, considering risk factors, comorbidities, and the different PsA phenotypes. Growing experience with these new agents allows novel treatment approaches that may improve clinical outcomes for PsA patients, in terms of remission/low disease activity and quality of life.

Psoriasis is a chronic inflammatory disease that can drastically affect a patient's quality-of-life and is associated with multiple comorbid conditions. The most common form of psoriasis is plaque psoriasis, commonly presenting as sharply demarcated, erythematous plaques with overlying silvery scale on the trunk, extensor surfaces, limbs, and scalp. Although initially limited to oral therapies, the choices in systemic therapies for moderate-to-severe plaque psoriasis have evolved with biologic immunotherapies being the main focus.

In this review, we describe the IL-23/Th17 axis and IL-23 inhibitors as targets for a growing family of biologics. This family includes the FDA-approved medications ustekinumab, guselkumab, tildrakizumab, and risankizumab. We will review the safety and efficacy of these medications throughout various Phase 1,2, and 3, trials for moderate-to-severe psoriasis. A literature search of PubMed was utilized for the following terms: 'psoriasis and IL-23,' 'ustekinumab,' 'guselkumab,' 'tildrakizumab,' and 'risankizumab.' We also searched for clinical trials involving IL-23 inhibitors registered at ClinicalTrials.gov.

Anti-IL 23 therapy, especially anti-p19 monoclonal antibodies, should be considered first-line therapy for moderate-to-severe plaque psoriasis due to their efficacy and relative safety. More research is required to expand the scope of anti-p19 therapy to pediatric populations and additional indications such as psoriatic arthritis.

Psoriatic patients present various infectious risk factors, but there are few studies in the literature evaluating the actual impact of psoriasis in severe staphylococcal skin infections. Our narrative review of the literature suggests that psoriatic patients are at increased risk of both colonization and severe infection, during hospitalization, by S. aureus. The latter also appears to play a role in the pathogenesis of psoriasis through the production of exotoxins. Hospitalized psoriatic patients are also at increased risk of MRSA skin infections. For this reason, new molecules are needed that could both overcome bacterial resistance and inhibit exotoxin production. In our opinion, in the near future, topical quorum sensing inhibitors in combination with current anti-MRSA therapies will be able to overcome the increasing resistance and block exotoxin production. Supplementation with Vitamin E (VE) or derivatives could also enhance the effect of anti-MRSA antibiotics, considering that psoriatic patients with metabolic comorbidities show a low intake of VE and low serum levels, making VE supplementation an interesting new perspective.