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Background Few studies have used real-world data to investigate the association between biologic therapy survival and age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. The robustness of these studies is limited by small sample size, short follow-up and diverse safety and effectiveness measures. Objectives To describe biologic survival and explore whether the response to biologics is modified by age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. Methods Data from patients in the UK and the Republic of Ireland registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007 to 2022 on a first course of adalimumab, etanercept, secukinumab or ustekinumab with at least 6 months' follow-up and a subset of BADBIR patients with available HLA-C*06:02 information registered to Biomarkers and Stratification To Optimise outcomes in Psoriasis (BSTOP) were analysed. Patients aged ≥ 50 years at treatment initiation were classified into early-onset psoriasis (EOP) (presenting in patients ≤ 40 years of age) and late-onset psoriasis (LOP) (presenting in patients > 40 years of age). BADBIR patients with available information in BSTOP were categorized as HLA-C*06:02− or HLA-C*06:02 +. Biologic survival was defined as treatment discontinuation associated with ineffectiveness or occurrence of adverse events (AEs). Adjusted survival function and hazard ratio (aHR) with 95% confidence interval (CI) were estimated using a flexible parametric model to compare discontinuing therapy between age at psoriasis onset and HLA-C*06:02 groups. Each model included exposure (biologics), effect modifier (age at onset or HLA-C*06:02 status), interaction terms and several baseline demographic, clinical and disease severity covariates. Results Final analytical cohorts included 4250 patients in the age at psoriasis onset group [2929 EOP (69%) vs. 1321 LOP (31%)] and 3094 patients in the HLA-C*06:02 status group [1603 HLA-C*06:02+ (52%) vs. 1491 HLA-C*06:02− (48%)]. There was no significant difference between EOP and LOP in drug survival associated with ineffectiveness or AEs for any biologics. However, compared with patients who were HLA-C*06:02−, patients who were HLA-C*06:02 + were less likely to discontinue ustekinumab for reasons associated with ineffectiveness (aHR 0.56, 95% CI 0.42–0.75). Conclusions HLA-C*06:02, but not age at psoriasis onset, is a predictive biomarker for biologic survival in patients with psoriasis. Findings from this large cohort provide further, important information to aid clinicians using biologic therapies to manage patients with psoriasis. [ABSTRACT FROM AUTHOR]

Background Tumour necrosis factor-alpha inhibitors (TNFi) have revolutionized the treatment of moderate-to-severe psoriasis. Following patent expiry of the originator biologics, TNFi biosimilars became available, presenting the opportunity for significant reductions in drug costs. Objectives To describe the uptake of TNFi biosimilars for psoriasis treatment in the UK and Ireland. Methods This observational cohort study utilizes data from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR), a national pharmacovigilance study register for patients with psoriasis on systemic treatments. We analysed biosimilar uptake trends over time in nine geographical regions of England along with Wales, Scotland, Northern Ireland and the Republic of Ireland. We assessed the incidence of switching to biosimilars in an originator-user cohort (switchers). Patients on originators infliximab, etanercept and adalimumab at the time originator patents expired, entered the cohort on 1 February 2015, August 2015 and October 2018, respectively, and were followed up until 31 October 2021. Trends in biosimilar initiations were assessed in an adalimumab-naïve cohort who started adalimumab between 1 October 2018 and 31 July 2019 (starters). We assessed the associations between patient factors and originator-to-biosimilar switching and biosimilar initiation using a multivariable Cox regression model and a multivariable logistic regression model, respectively. Results Included in the originator-user cohort were 4202 patients (209 on infliximab, 742 on etanercept and 3251 on adalimumab). For infliximab, etanercept and adalimumab, respectively, the cumulative incidence of originator-to-biosimilar switching increased with time to 14.8%, 23.6% and 66.6% after 3 years. Across geographical regions, 3-year switching rates varied from 0% to 43.7% for infliximab; from 0% to 40.4% for etanercept; and from 12.5% to 84.3% for adalimumab. Out of the 528 patients included in the adalimumab-naïve cohort, 67.8% started on biosimilars. Originator-to-biosimilar switching and biosimilar initiation were more common in men and in patients who had lower Psoriasis Area and Severity Index at cohort entry. Conclusions The uptake of biosimilars increased over time and varied considerably across the UK and Ireland; adalimumab had the highest biosimilar uptake rate compared with that of other TNFi drugs. [ABSTRACT FROM AUTHOR]

Summary: Background: Patients with psoriasis are often concerned about the risk of serious infection associated with systemic psoriasis treatments. Objectives: To develop and externally validate a prediction model for serious infection in patients with psoriasis within 1 year of starting systemic therapies. Methods: The risk prediction model was developed using the British Association of Dermatologists Biologic Interventions Register (BADBIR), and the German Psoriasis Registry PsoBest was used as the validation dataset. Model discrimination and calibration were assessed internally and externally using the C‐statistic, the calibration slope and the calibration in the large. Results: Overall 175 (1·7%) out of 10 033 participants from BADBIR and 41 (1·7%) out of 2423 participants from PsoBest developed a serious infection within 1 year of therapy initiation. Selected predictors in a multiple logistic regression model included nine baseline covariates, and starting infliximab was the strongest predictor. Evaluation of model performance showed a bootstrap optimism‐corrected C‐statistic of 0·64 [95% confidence interval (CI) 0·60–0·69], calibration in the large of 0·02 (95% CI −0·14 to 0·17) and a calibration slope of 0·88 (95% CI 0·70–1·07), while external validation performance was poor, with C‐statistic 0·52 (95% CI 0·42–0·62), calibration in the large 0·06 (95% CI −0·25 to 0·37) and calibration slope 0·36 (95% CI −0·24 to 0·97). Conclusions: We present the first results of the development of a multivariable prediction model. This model may help patients and dermatologists in the U.K. and the Republic of Ireland to identify modifiable risk factors and inform therapy choice in a shared decision‐making process. What's already known about this topic? Patients and their clinicians are often concerned about the risk of serious infection associated with biological therapies for the treatment of psoriasis.However, there are no current tools available to estimate an individual's risk of serious infection when starting a systemic therapy. What does this study add? This study found that the serious infection risk prediction model had good calibration and moderate discriminationThe model included chronic obstructive pulmonary disease, alcohol intake, number of comorbidities and employment status, in addition to age, sex, Psoriasis Area and Severity Index, choice of starting therapy and body mass index.These are the first results of the multivariable prediction model, which may help patients and dermatologists in the U.K. and the Republic of Ireland to identify modifiable risk factors and inform therapy choice in a shared decision‐making process. Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]

Importance: Patients with psoriasis enrolled in clinical trials of biologics may not be representative of the real-world population. There is evidence that patients ineligible for such trials have a greater risk of serious adverse events (SAEs), but the effect on drug discontinuation and effectiveness are unknown., Objective: To determine whether (1) drug discontinuation, (2) effectiveness, and (3) rates of SAEs differ in patients with psoriasis categorized as eligible or ineligible for clinical trials., Design, Setting, and Participants: An observational study using 157 dermatology centers in the United Kingdom and Republic of Ireland was carried out wherein we applied the eligibility criteria of clinical trials of biologic therapies for psoriasis to patients who were being followed up in the British Association of Dermatologists Biologic Interventions Register (BADBIR) and being prescribed biologics as part of standard clinical care. Patients with psoriasis registered to BADBIR who were taking etanercept (enbrel only; n = 1509), adalimumab (n = 4000), and ustekinumab (n = 1627) with at least 1 follow-up visit. Eligibility criteria were extracted from phase 3 licensing trials for etanercept, adalimumab, and ustekinumab for the treatment of moderate to severe psoriasis. Patients in BADBIR with a missing baseline Psoriasis Area and Severity Index (PASI) or baseline PASI value less than 10 (etanercept) or less than 12 (adalimumab; ustekinumab) but who would otherwise be eligible were investigated separately. Eligibility categories applied to BADBIR included: eligible, ineligible, insufficient baseline PASI only, and missing baseline PASI only., Main Outcomes and Measures: (1) Drug discontinuation: cumulative incidence at 12 months by stop reason per eligibility category and drug; (2) effectiveness: linear regression of absolute change in PASI from baseline to 6 and 12 months; and (3) SAEs: incidence rate ratio (IRR) at 12 months between eligibility categories per drug., Results: The mean (SD) age of the 7136 patients included in the analysis was 45 (13) years and 2924 (41%) were women and 4212 (59%) were men. Of 7136 patients, 839 (56%) etanercept, 2219 (56%) adalimumab, and 754 (46%) ustekinumab registrations were categorized as eligible. The most common reasons for ineligibility were diabetes (etanercept, 143 [9%]; ustekinumab, 201 [12%]) and nonchronic plaque psoriasis (adalimumab, 157 [4%]). Patients categorized as ineligible (etanercept, 367 [24%]; adalimumab, 282 [7%]; ustekinumab, 394 [24%]) achieved a smaller absolute change in PASI after 6 and 12 months (adalimumab, ustekinumab), and had significantly higher rates of SAEs compared with the eligible category (etanercept: IRR, 1.9; 95% CI, 1.4-2.6; adalimumab: IRR, 2.0; 95% CI, 1.5-2.6; ustekinumab: IRR, 2.8; 95% CI, 2.1-3.8). No significant differences in drug discontinuation were observed between categories., Conclusions and Relevance: Clinical trial effectiveness and safety outcomes are not representative of real-world patients in BADBIR patients categorized as ineligible for such trials.