Kathleen McElhone

Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Drug survival reflects a drugs effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09-1.37), being a current smoker (HR 1.19; 95% CI: 1.03-1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00-1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71-0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45-1.84) or infliximab (HR 1.56; 95% CI: 1.16-2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37-0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.

The British Association of Dermatologists’ Biologic Interventions Register (BADBIR): design, methodology and objectives

Background  The British Association of Dermatologists (BAD) established a web‐based pharmacovigilance register to assess the long‐term safety of biologics prescribed for patients with severe psoriasis in September 2007. The BAD Biologic Interventions Register (BADBIR) also participates in the network of European psoriasis biologics registers (Psonet).

Oral liarozole in the treatment of palmoplantar pustular psoriasis: A randomized, double-blind, placebo-controlled study

Background Palmoplantar pustular psoriasis (PPP) is a chronic, relapsing condition often recalcitrant to therapy. Synthetic retinoids have been found to be efficacious in the treatment of PPP, but their use is limited by side‐effects. Liarozole is an imidazole‐like compound that inhibits the retinoic acid (RA) 4‐hydroxylase‐mediated breakdown of all‐trans RA, causing elevation of plasma and cutaneous levels of RA. Thus liarozole acts as a retinoid‐mimetic drug. Liarozole has already been found to be effective in the treatment of retinoid‐responsive conditions such as chronic plaque psoriasis and ichthyoses.

Demographics and disease characteristics of patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register

The British Association of Dermatologists Biologic Interventions Register (BADBIR) is a prospective, observational cohort designed to assess the long‐term safety of biologic and conventional systemic therapies used for adults with moderate‐to‐severe psoriasis in the U.K. and Republic of Ireland.

Patterns of biologic therapy use in the management of psoriasis: cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)

Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the patterns of usage are incompletely defined.

Comparative effectiveness of biological therapies on improvements in quality of life in patients with psoriasis

Evidence of the comparative effectiveness of biological therapies for psoriasis on health‐related quality of life (HRQoL) in routine clinical practice is limited.

Identification of factors that may influence the selection of first-line biological therapy for people with psoriasis: a prospective, multicentre cohort study

The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium has a collective aim to develop a prescribing algorithm to help stratify eligible patients with psoriasis to the most appropriate biological treatment. To facilitate the adoption of a stratified approach, it is necessary to first understand the factors driving the choice of first‐line biological therapy.

Differential Drug Survival of Second-Line Biologic Therapies in Patients with Psoriasis: Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)

Little is known about the drug survival of second-line biologic therapies for psoriasis in routine clinical practice. We assessed drug survival of second-line biologic therapies and estimated the risk of recurrent discontinuation due to adverse events or ineffectiveness in patients with psoriasis who had failed a first biologic therapy and switched to a second in a large, multicenter pharmacovigilance registry (n = 1,239; adalimumab, n = 538; etanercept, n = 104; ustekinumab, n = 597). The overall drug survival rate in the first year after switching was 77% (95% confidence interval = 74–79%), falling to 58% (55–61%) in the third year. Female sex, multiple comorbidities, concomitant therapy with cyclosporine, and a high Psoriasis Area and Severity Index at switching to the second-line biologic therapy were predictors of overall discontinuation (multivariable Cox proportional hazard model). Compared to adalimumab, patients receiving etanercept were more likely to discontinue therapy (hazard ratio = 1.87, 95% confidence interval = 1.24–2.83), whereas patients receiving ustekinumab were more likely to persist (hazard ratio = 0.46; 95% confidence interval = 0.33–0.64). Discontinuation of the first biologic therapy because of adverse events was associated with an increased rate of second drug discontinuation because of adverse events (hazard ratio = 2.55; 95% confidence interval = 1.50–4.32). In conclusion, drug survival rates differed among biologic therapies and decreased over time; second-line discontinuation because of adverse events was more common among those who discontinued first-line treatment for this reason. The results of this study should support clinical decision making when choosing second-line biologic therapy for patients with psoriasis.

Comparison of Drug Discontinuation, Effectiveness, and Safety Between Clinical Trial Eligible and Ineligible Patients in BADBIR

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.

Generating EQ-5D-3L Utility Scores from the Dermatology Life Quality Index: A Mapping Study in Patients with Psoriasis

OBJECTIVES To develop an algorithm to predict the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) utility scores from the Dermatology Life Quality Index (DLQI) in psoriasis. METHODS This mapping study used data from the British Association of Dermatologists Biologic Interventions Register-a pharmacovigilance register comprising patients with moderate to severe psoriasis on systemic therapies. Conceptual overlap between the EQ-5D-3L and DLQI was assessed using Spearman rank correlation coefficients and exploratory factor analysis. Six regression methods to predict the EQ-5D-3L index (direct mapping) and two regression methods to predict EQ-5D-3L domain responses (response mapping) were tested. Random effects models were explored to account for repeated observations from the same individual. Estimated and actual EQ-5D-3L utility scores were compared using 10-fold cross-validation (in-sample) to evaluate predictive performance. Final models were selected using root mean squared error, mean absolute error, and mean error. RESULTS The data set comprised 22,085 observations for which DLQI and EQ-5D-3L were recorded on the same day. A moderate correlation was found between the measures (r = -0.47). Exploratory factor analysis showed that two EQ-5D-3L domains (pain/discomfort and depression/anxiety) were associated with all six DLQI domains. The best-performing model used ordinary least squares with DLQI items, age, and sex as explanatory variables (with squared, cubic, and interaction terms). A tool was produced to allow users to map their data to the EQ-5D-3L, and includes algorithms that require fewer variables (e.g., total DLQI scores). CONCLUSIONS This study produced mapping algorithms that can generate EQ-5D-3L utility scores from DLQI data for economic evaluations of health interventions for patients with psoriasis.