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

Background: Age of psoriasis onset is bimodally distributed with distinct peaks at <40 (early onset) and ≥40 years (late onset). Although age of psoriasis onset is associated with distinct disease profiles, few well-controlled studies report efficacy of biologics in patients with early- vs late-onset disease. Efficacy and safety of tildrakizumab, an interleukin-23 p19 inhibitor, for the treatment of moderate-to-severe plaque psoriasis were investigated in the Phase 3 trials reSURFACE 1 and reSURFACE 2.

Objectives: To determine 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 ≥50 years of age were grouped by age of psoriasis onset at <40 vs ≥40 years. Efficacy endpoints included absolute Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), and proportions of patients who achieved a ≥75%/≥90%/100% improvement from baseline in PASI (PASI 75/90/100), 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 from treatment-emergent adverse events (TEAEs).

Results: Higher percentages and adjusted responder rate estimates of patients with late- (n = 130) vs early-onset psoriasis (n = 111) achieved absolute PASI <1 (36.2% vs 27.9%; estimate, 32.2% vs 25.0%), PASI 90 (50.8% vs 39.6%; estimate, 49.4% vs 40.2%), and PASI 100 (21.5% vs 8.1%; estimate, 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 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. Among patients with early- vs late-onset psoriasis, TEAEs and serious TEAEs occurred in 65.8% vs 66.2% and 3.6% vs 6.9%, respectively.

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

Clinical trial registration: NCT01722331 and NCT01729754.