O03: Effect modification of biologic survival by patient characteristics: a prospective cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register

Zenas Yiu,¹ Gabrielle Becher,² Brian Kirby,³ Philip Laws,⁴ Nick Reynolds,⁵ Catherine Smith,⁶ Mark Lunt,⁷ Richard Warren¹ and Christopher Griffiths¹

¹Centre for Dermatology Research, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, UK; ²West Glasgow Ambulatory Care Hospital, Glasgow, UK; ³Charles Department of Dermatology, St Vincent’s University Hospital, Dublin, Ireland and School of Health Sciences and Charles Institute, University College Dublin, Dublin, Ireland; ⁴Department of Dermatology, The Leeds Teaching Hospitals NHS Trust, Leeds, UK; ⁵Institute of Translational and Clinical Medicine, Newcastle University Medical School and Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; ⁶St John’s Institute of Dermatology, NIHR Biomedical Research Centre, Guy’s & St Thomas’ NHS Foundation Trust, Kings College London, London, UK; and ⁷Versus Arthritis Centre for Epidemiology, The University of Manchester, Manchester, UK

Drug survival is a proxy measure for treatment effectiveness. Effect modification describes whether the effect of a treatment is different in groups of patients with different characteristics. We aimed to assess whether drug survival of the biologics adalimumab, guselkumab, ixekizumab, secukinumab and ustekinumab, used for the treatment of plaque psoriasis, differed between groups defined by patient baseline characteristics. We conducted a prospective cohort study using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2021. We fitted a flexible parametric survival model for drug survival, limited the outcome to discontinuation due to ineffectiveness and allowed for time-varying effects. We included covariates that were known to be associated with biologic survival from our previous and other published studies. We investigated for potential effect modification by categorical covariates that were selected in these models using sequential likelihood ratio tests comparing models with and without an interaction term between the covariate and choice of biologic. In total, 6607 (41.0%) patients started on adalimumab, 5405 (33.5%) on ustekinumab, 2677 (16.6%) on secukinumab, 730 (4.5%) on guselkumab and 703 (4.4%) on ixekizumab. There was evidence of effect modification by psoriatic arthritis (PsA); nail involvement; previous experience with biologics; and ethnicity. People with PsA or nail involvement had a lower drug survival on ustekinumab than those without PsA or nail involvement [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.03–1.35)], while drug survival of adalimumab, guselkumab, ixekizumab or secukinumab did not differ significantly with or without PsA or nail involvement. Asian patients had lower drug survival on adalimumab than white patients (HR 1.59, 95% CI 1.29–1.94), but not to any other biologic assessed here. The drug survival of ixekizumab in biologic-naïve patients was not significantly different from biologic-naïve patients on guselkumab (HR 3.89, 95% CI 0.73–20.73), while biologic-naïve patients on secukinumab had similar drug survival to biologic-naïve patients on ustekinumab (HR 1.22, 95% CI 0.96–1.53). However, patients on either interleukin-17A inhibitor (secukinumab or ixekizumab) as a third- or subsequent-line therapy had lower drug survival than third- or subsequent-line ustekinumab [secukinumab HR 1.85 (95% CI 1.46–2.35); ixekizumab HR 2.07 (95% CI 1.39–3.08)]. We identified PsA, nail involvement, previous biologic exposure and ethnicity as factors that have a differential effect on drug survival dependent on the choice of biological therapy. This information on longer-term treatment effect may help patients and their clinicians to make an informed decision when starting a biological therapy for psoriasis.