Efficacy and safety of tildrakizumab in patients with early- vs. late-onset psoriasis.

Background: The age of psoriasis onset is bimodally distributed with distinct peaks at < 40 (early onset) and ≥ 40 years (late onset) of age. Although the age of psoriasis onset is associated with distinct disease profiles, few well-controlled studies have reported the efficacy of biologics in patients with early- vs. late-onset disease. The efficacy and safety of tildrakizumab, an interleukin-23 p19 inhibitor, for the treatment of moderate-to-severe plaque psoriasis were investigated in the reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) phase III trials.

Objectives: To determine the efficacy and safety of tildrakizumab in patients with early- vs. late-onset psoriasis through 28 weeks of treatment.

Methods: This was a post hoc subgroup analysis of patients from reSURFACE 1 and reSURFACE 2. Patients aged ≥ 50 years were grouped by age of psoriasis onset (< 40 years vs. ≥ 40 years). Efficacy endpoints included absolute Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), and the proportions of patients who achieved a ≥ 75%, ≥ 90% or 100% improvement from baseline in PASI (PASI 75, PASI 90 and PASI 100, respectively), a Physician Global Assessment score of 0 or 1 (PGA 0/1) and DLQI of 0 or 1 (DLQI 0/1), adjusted for potential confounders. Safety was assessed based on treatment-emergent adverse events (TEAEs).

Results: Higher percentages and adjusted responder rate estimates of patients with late- (n = 130) vs. early-onset (n = 111) psoriasis achieved an absolute PASI < 1 (36.2% vs. 27.9%; estimate was 32.2% vs. 25.0%), PASI 90 (50.8% vs. 39.6%; estimate was 49.4% vs. 40.2%) and PASI 100 (21.5% vs. 8.1%; estimate was 13.7% vs. 7.9%) at week 28 (all P < 0.05). Age of onset did not significantly affect change from baseline in absolute PASI or DLQI, or the achievement of PASI < 5, PASI < 3, PASI 75, DLQI 0/1 or PGA 0/1 (all P > 0.05). Efficacy findings were supported in a subset of patients matched by disease duration. TEAEs and serious TEAEs occurred in 65.8% vs. 66.2% and 3.6% vs. 6.9% of patients with early- vs. late-onset psoriasis, respectively.

Conclusions: Treatment with tildrakizumab was effective with no safety signals found in either of the patient subgroups. Patients with late-onset psoriasis were more likely to achieve complete or near-complete clearance than patients with early-onset psoriasis.