Effect Modification of Biologic Survival by Patient Characteristics: A Step Towards Precision Medicine in the Treatment of Psoriasis

Background: Drug survival, a measure of the time between the initiation and cessation of treatment, is a proxy measure for treatment effectiveness. 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.

Objectives: To Identify baseline patient characteristics that may act as effect modifiers for biologics used for the treatment of psoriasis and their survival.

Methods: We conducted a prospective cohort study using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a large, ongoing pharmacovigilance registry of psoriasis patients in the UK and RoI, 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 previously known to be associated with biologic survival, and investigated for potential effect modification by categorical covariates between biologic and their survival.

Results: 6,607 (41.0%) patients started on adalimumab, 5,405 (33.5%) ustekinumab, 2,677 (16.6%) secukinumab, 730 (4.5%) guselkumab, and 703 (4.4%) on ixekizumab. People with psoriatic arthritis(PsA) or nail involvement had a lower drug survival than those without PsA or nail involvement for ustekinumab only (hazard ratio [HR] 1.18, 95% confidence interval[CI] 1.03-1.35). Asian patients had a lower drug survival compared with white patients for adalimumab only (HR 1.59, 95%CI 1.29-1.94). The drug survival of ixekizumab in biologic-naïve patients was not significantly different from biologic-naïve patients on guselkumab, which had the highest overall drug survival (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 3rd or subsequent-line therapy had a lower drug survival compared with 3rd or subsequent-line ustekinumab (secukinumab HR 1.85, 95%CI 1.46-2.35; ixekizumab HR 2.07, 95%CI 1.39-3.08).

Conclusions: In conclusion, 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 biologic therapy. This information on the longer-term treatment effect may help patients and their clinicians to make an informed decision when starting a biologic therapy for psoriasis, and thus help patients choose the right therapy for them the first time.