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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.)