Randomized Trial Replication Using Observational Data for Comparative Effectiveness of Secukinumab and Ustekinumab in Psoriasis: a study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)

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  • BADBIR Study Group

Abstract

Importance: The effectiveness of treatments for psoriasis in everyday practice may be lower than that found in clinical trials. By designing an analysis plan to emulate an ideal “target” trial, data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) can provide estimates that are robust and inform both clinicians and regulatory bodies.

Objective: 1. To assess the comparative effectiveness of ustekinumab and secukinumab in patients with psoriasis; 2. To test whether the relative effectiveness estimate can replicate that of the CLEAR study, a randomized controlled trial (RCT) which compared secukinumab to ustekinumab for psoriasis.

Design: The prospective cohort study was performed using data from BADBIR between November 2007 and August 2019. Propensity score 1:1 matched analysis and inverse probability treatment weighted analysis were performed.

Setting: Multicenter longitudinal pharmacovigilance register of patients with moderate-to-severe psoriasis in the United Kingdom and Republic of Ireland.

Participants: 1,231 included, 917 on ustekinumab and 314 on secukinumab; 311 included in each cohort in the PS matched analysis.

Main Outcomes and Measures: 1. Risk ratio (RR) and risk difference (RD) for achieving Psoriasis Area and Severity Index (PASI) ≤2 at 12 months for secukinumab compared with ustekinumab. Methods to account for missing outcome included: complete case analysis; non-responder imputation; last observation carried forward; inverse probability of censoring weighting; and multiple imputation. 2. Whether the effect estimates reached regulatory or estimate agreement with CLEAR.

Results: Secukinumab was superior to ustekinumab in all analyses, except non-responder imputation, in the proportion of participants achieving PASI ≤2 (RR 1.28 [95%CI 1.06-1.55]; RD 11.9% [1.6-22.1] in the PS weighted complete case analysis). All analyses, apart from non-responder imputation, reached regulatory agreement in both propensity score approaches.

Conclusions and Relevance: Treatment with secukinumab results in a higher proportion of patients in BADBIR reaching a PASI ≤2 after 12 months of therapy as compared to ustekinumab. Target trial emulation in this comparative effectiveness study in BADBIR resulted in regulatory and estimate agreement with the corresponding RCT. Further such studies may help fill the evidence gap when comparing other systemic therapies for psoriasis.


Bibliographical metadata

Original languageEnglish
JournalJAMA dermatology
DOIs
Publication statusAccepted/In press - 12 Sep 2020