Efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 64-week phase 3 study (reSURFACE 1)

Abstract

Tildrakizumab is a high-affinity, humanized immunoglobulin G1κ, anti-interleukin-23p19 monoclonal antibody recently approved in Japan for treatment of plaque psoriasis. We report results from Japanese patients treated with tildrakizumab in the multinational, randomized, double-blind, placebo-controlled reSURFACE 1 study (clinicaltrials.gov NCT01722331). Adults with moderate to severe plaque psoriasis were randomized (2:2:1) to receive subcutaneous tildrakizumab 100 or 200 mg or placebo every 12 weeks. Placebo recipients were rerandomized to tildrakizumab 100 or 200 mg at week 12. The global study coprimary endpoints were the proportions of patients achieving 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) and Physician Global Assessment (PGA) response (0/1 with ≥2 grade reduction from baseline) at week 12. Analyses included 158 Japanese patients randomized to tildrakizumab 100 (n = 64) or 200 mg (n = 62) or placebo (n = 32). Japanese patients had higher mean baseline body surface area involvement and PASI versus all reSURFACE 1 patients. At week 12, significantly more Japanese patients receiving tildrakizumab 100 and 200 mg versus placebo achieved PASI 75 (54.7% and 54.8% vs 6.3%, respectively, both nominal p < 0.001) and PGA 0/1 response (54.7% and 56.5% vs 9.4%, respectively, both nominal P < 0.001). Response rates increased over time with maximal efficacy after 22-28 weeks; >80% of patients achieving PASI 75 or PASI 90 at week 28 and continuing tildrakizumab treatment at the same dose maintained response at week 64. From baseline to week 28, absolute PASI decreased from >12 in all patients to ≤2 in >40% and ≤3 in >50% of patients receiving tildrakizumab. Tildrakizumab was generally well tolerated with an adverse event profile similar to that of placebo. Tildrakizumab treatment was associated with durable efficacy in Japanese patients with moderate to severe plaque psoriasis despite greater baseline disease severity versus the global reSURFACE 1 population.

Keywords: Japanese; antibodies; humanized; interleukin-23 subunit p19; monoclonal; psoriasis; randomized controlled trial; tildrakizumab.

Figure 1

Patient disposition

Figure 2

Proportions of patients achieving (a) PASI 75, (b) PGA 1 or 0 with ≥2 grade decrease from baseline, (c) PASI 90, and (d) PASI 100 through week 28. PASI, Psoriasis Area and Severity Index; PBO, placebo; PGA, Physician Global Assessment; TIL, tildrakizumab

Figure 3

Proportions of patients who maintained (a) PASI 75 and (b) PASI 90 responses from week 28 through week 64. PASI, Psoriasis Area and Severity Index; TIL, tildrakizumab

Figure 4

Distribution of PASI scores at baseline and week 28 among patients treated with (a) tildrakizumab 100 mg and (b) tildrakizumab 200 mg, and distributions of PASI scores at baseline and week 64 among patients who were responders or partial responders at week 28 receiving (c) tildrakizumab 100 mg or (d) tildrakizumab 200 mg at week 64. PASI, Psoriasis Area and Severity Index