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Background: Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR. Efficacy was generally consistent between TNFi-naïve and TNFi-experienced cohorts; however, in the latter, higher response rates have been observed with the Q4W dosing regimen relative to the Q8W dosing regimen for some endpoints, suggesting the need to evaluate whether more frequent dosing may provide an incremental clinical benefit for TNFi-IR patients., Methods: The phase 3b SOLSTICE study will assess guselkumab efficacy and safety in TNFi-IR PsA patients. Eligibility criteria include a PsA diagnosis for ≥ 6 months; active disease (≥ 3 swollen, ≥ 3 tender joints, C-reactive protein ≥ 0.3 mg/dL); and inadequate efficacy with, and/or intolerance to, one prior TNFi. Participants will be randomized 1:1:1 to guselkumab Q4W or Q8W or placebo→guselkumab Q4W (at Week 24). The primary endpoint is the proportion of patients achieving ≥ 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 24. Major secondary endpoints include ACR50, ACR70; an Investigator's Global Assessment (IGA) of psoriasis score of 0/1 plus ≥ 2-grade reduction and ≥ 90% improvement in Psoriasis Area and Severity Index (both among patients with ≥ 3% body surface area affected by psoriasis and baseline IGA ≥ 2); minimal/very low disease activity; and changes from baseline in Health Assessment Questionnaire-Disability Index, the 36-item Short-Form Health Survey Physical Component Summary, and Functional Assessment of Chronic Illness Therapy-Fatigue scores. The target sample size (N = 450) is estimated to provide > 90% power in detecting differences between each guselkumab group and the placebo group for the primary endpoint assuming a 2-sided α = 0.05. Cochran-Mantel-Haenszel testing and analyses of covariance will be used to compare efficacy for binary and continuous endpoints, respectively., Discussion: Findings from the phase 3b SOLSTICE study, the design of which was informed by results from previously conducted phase 3 studies, is expected to provide important efficacy and safety information on guselkumab therapy in TNFi-IR patients with PsA., Trial Registration: This trial was registered at ClinicalTrials.gov, NCT04936308, on 23 June 2021., (© 2024. The Author(s).)

Background: Patterns of psoriasis characteristics by sex are not fully understood. Objective: Evaluate patient characteristics by sex at enrollment in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods: Two PSOLAR cohorts were evaluated by sex: patients who were biologic-naïve (n = 3329) and patients who were systemic therapy-naïve (n = 1290) at entry. Baseline demographic and disease characteristics, medical history, social activity, and lifestyle risk factors were collected for all patients and were compared between males and females using an independent samples t-test for continuous variables and chi-square tests for categorical variables. Results: In both cohorts, disease duration was similar for males and females; however, disease severity based on baseline Physician Global Assessment and body surface area of psoriasis was greater in males versus females ( P < .05). Baseline Dermatology Life Quality Index scores were higher for biologic-naïve females than for males ( P = .008). In both cohorts, females were significantly more likely than males to have a history of anxiety, depression, and cancer excluding nonmelanoma skin cancer, to have received systemic steroid therapy, and to have health insurance; males were significantly more likely than females to have a history of cardiovascular disease, smoking, and alcohol consumption, and to work full time. Conclusions: Based on patient data obtained at entry into PSOLAR, significant differences in psoriasis disease characteristics, and medical, family, and social history-related variables were observed between males and females. Among systemic therapy-naïve patients, there was a greater negative impact on quality of life for females compared with males, despite generally lower objective disease severity for females., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.G. has nothing to disclose. R.C. has nothing to disclose. W.L. is employed by Janssen Research & Development, LLC and owns stock in Johnson & Johnson, of which Janssen is a subsidiary. K.P.L. is employed by Janssen Scientific Affairs, LLC and owns stock in Johnson & Johnson, of which Janssen is a subsidiary. M.G. has been an investigator, speaker, consultant, or advisory board member for AbbVie, Actelion, Akros, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Galderma, GSK, Eli Lilly, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, UCB, and Valeant/Bausch. E.M.G.J.dJ. has received research grants from AbbVie, Novartis, Janssen Pharmaceutica, Leo Pharma, and UCB, and has acted as consultant and/or paid speaker for and/or participated in research sponsored by companies that manufacture drugs used for the treatment of psoriasis including AbbVie, Almirall, Janssen Pharmaceutica, Novartis, Lilly, Celgene, Leo Pharma, Sanofi, UCB, and Galapagos. Funding received by E.M.G.J.dJ. is not personal but goes to the independent research fund of the Department of Dermatology of the Radboud University Medical Center, Nijmegen, the Netherlands. B.S. serves as a consultant for AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corporation, Dermavant, Eli Lilly, GlaxoSmithKline, Immunic Therapeutics, Janssen, LEO Pharma, Maruho, Meiji Seika Pharma, Mindera, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma, and UCB Pharma; a paid speaker for AbbVie, Eli Lilly, Janssen, and Sanofi-Genzyme/Regeneron; receives a consulting fee as a co-scientific director for the CorEvitas Psoriasis Registry; and an investigator for AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Dermira and Novartis., (© The Author(s) 2022.)

Introduction: Psoriasis Longitudinal Assessment and Registry (PSOLAR) was designed in 2007 as the first disease-based registry for patients with psoriasis., Objective: The aim of this study was to discuss methodological limitations and post hoc analyses in long-term safety registries using learnings from analyses of a potential safety risk for major adverse cardiovascular events (MACE) in PSOLAR., Methods: PSOLAR is an international observational study of over 12,000 psoriasis patients that was conducted to meet postmarketing safety commitments for infliximab and ustekinumab. A recent annual review of registry data indicated a potential MACE risk for ustekinumab vs. non-biologics based on prespecified COX model regression analyses, which yielded an adjusted hazard ratio (HR) of 1.533 (95% confidence interval [CI] 1.103-2.131). Therefore, we conducted a comprehensive review of key statistical methodology and implemented post hoc analytical methods to address specific limitations., Results: The following limiting factors were identified: (1) inclusion of both prevalent and incident (new) users of biologics; (2) unanticipated imbalances in patient characteristics between treatment cohorts at baseline; (3) limited availability of relevant clinical data after enrollment; and (4) divergence of characteristics associated with outcomes among comparator groups over time. The analysis was modified to include only incident users, propensity scores were used to weight HRs, and adalimumab was deemed a more clinically appropriate comparator. The revised HR was 0.820 (95% CI 0.532-1.265), indicating no meaningful increase in MACE risk for ustekinumab., Conclusion: Our results, which do not support a causal association between ustekinumab exposure and MACE risk, underscore the need for ongoing assessment of analytical methods in long-term observational studies.

Importance: Prospective data are limited on pregnancy outcomes among women with psoriasis who may be receiving biologic or conventional systemic therapy., Objective: To report pregnancy outcomes observed in the Psoriasis Longitudinal Assessment and Registry (PSOLAR)., Design, Setting, and Participants: This cohort study used data from PSOLAR, a multicenter, disease-based, observational registry evaluating long-term safety and clinical outcomes for patients receiving or eligible to receive treatment for psoriasis with biologics and/or conventional systemic therapies. Of 12 090 enrollees, 5456 were women (45.1%), and 2224 women were of childbearing age (18-45 years). Participants had a total of 12 929 patient-years of follow-up (median, 7.2 [range, 3.3-8.0] years per patient). Data were collected from June 20, 2007, to August 23, 2019, and analyzed from April 23 to June 23, 2020., Exposures: Exposure to biologics within the prenatal period (≤1 year before birth or ≤6 months before spontaneous abortion) or at any other time., Main Outcomes and Measures: Descriptive summaries of pregnancies and pregnancy-related outcomes were self-reported in PSOLAR, including births, stillbirths, spontaneous abortions, and elective terminations. Live birth characteristics collected in PSOLAR include whether a birth was full-term (≥37 weeks) or premature (<37 weeks) and whether neonatal adverse events or congenital anomalies occurred., Results: A total of 298 pregnancies occurred among 220 women (mean [SD] age, 27.8 [5.2] years), and the general fertility rate was 18.9 per 1000 women aged 18 to 45 years. Of the 298 pregnancies, 244 (81.9%) resulted in birth, 41 (13.8%) ended in spontaneous abortion, and 13 (4.4%) were electively terminated. Gestational age was available for 243 births; 221 infants (90.9%) were full-term, and 22 (9.1%) were born prematurely. Birth outcomes included 231 healthy newborns, 10 infants with a neonatal problem, 2 infants with a congenital anomaly, and 1 stillbirth. Of the 298 pregnancies, 252 were associated with biologic exposure before or during pregnancy. Pregnancy outcomes for women exposed to biologics were similar to those for women exposed to nonbiologics. Among women who became pregnant, mean (SD) age at the time of pregnancy outcome was 30.9 (4.8) years; at enrollment into the registry, 74 of 219 (33.8%) had obesity, and 121 of 220 (55.0%) were past or current smokers., Conclusions and Relevance: The findings of this cohort study suggest that pregnancy outcomes in PSOLAR have remained consistent with previous reports. Overall and live birth outcomes were similar to those for the general population.

Background: The effects of systemic therapy on mortality risk among patients with psoriasis are not fully understood., Objective: To evaluate the impact of systemic treatment on mortality risk in patients enrolled in the Psoriasis Longitudinal Assessment and Registry., Methods: Nested case-control analyses were performed to estimate mortality risk. Cases were defined as patients who died while participating in the Psoriasis Longitudinal Assessment and Registry. Cases were matched (1:4) with controls by age, race, sex, and geographic region. Evaluated treatments included methotrexate, ustekinumab, and tumor necrosis factor α inhibitors. Exposure was defined as at least 1 dose of treatment within 3 months before death and was stratified by duration of therapy., Results: Among 12,090 patients, 341 deaths occurred, matched to 1364 controls. Biologic treatment within the preceding 3 months was protective against mortality versus no exposure: odds ratio (OR) for exposure of less than 1 year, 0.08 (95% confidence interval [CI], 0.03-0.23); OR for exposure of 1 year or longer, 0.09 (95% CI, 0.06-0.13). Methotrexate was protective against mortality only with exposure for 1 year or longer (OR, 0.08; 95% CI, 0.02-0.28)., Limitations: Observational studies are subject to unmeasured confounding., Conclusions: Biologic therapy was associated with reduced mortality risk in patients with moderate to severe psoriasis, regardless of treatment duration; methotrexate reduced risk only with exposure for 1 year or longer., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)