AB0955 Tildrakizumab efficacy over time by week 28 response levels in two phase 3 clinical trials in patients with chronic plaque psoriasis

Abstract

Background: Tildrakizumab (TIL), a humanized, IgG1/kappa monoclonal antibody for IL-23p19, recently demonstrated efficacy in subjects with chronic plaque psoriasis in 2 phase 3 clinical studies. In this analysis, we examined efficacy from baseline to week 52 among TIL patients achieving various Psoriasis Area and Severity Index (PASI) responses at week 28. Method(s): ReSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) were double-blind randomized controlled studies in subjects with moderate-to-severe chronic plaque psoriasis. Part 1 (0-12 weeks) was placebo controlled; part 2 (12-28 weeks) rerandomized placebo patients to TIL; part 3 (28-64 weeks, reSURFACE 1; 28-52 weeks, reSURFACE 2) patients with >=PASI 50 were rerandomized to continue or increase TIL dose or to placebo based on response at week 28. In this pooled analysis, patients consistently on TIL 100 mg and 200 mg from baseline to week 52 were classified in 5 mutually exclusive groups based on their week-28 PASI response: PASI <50, PASI 50-74, PASI 75-89, PASI 90-99, and PASI 100. Baseline characteristics and % PASI improvement from baseline up to week 52 (observed data) were examined for each group. Result(s): This analysis included 575 (TIL 100 mg) and 581 (TIL 200 mg) patients; the overall pooled week 28 PASI 75/90/100 responses were 77%/54%/23% (TIL 100 mg) and 78%/58%/29% (TIL 200 mg). At week 28, 133 (23.1%), 175 (30.4%), 137 (23.8%), 82 (14.3%), and 48 (8.3%) TIL 100 mg patients and 170 (29.3%), 169 (29.1%), 114 (19.6%), 105 (18.1%), and 23 (4.0%) TIL 200 mg achieved PASI 100, PASI 90-99, PASI 75-89, PASI 50-74, and PASI <50, respectively. On average, PASI 100 patients were younger, lighter, and had shorter disease duration at baseline compared with other response groups. For TIL 100 mg, % PASI improvement was highest for PASI 100 and least for PASI <50 patients for all visits up to week 28 (week 4: 53%, 46%, 38%, 30%, and 16%; week 28: 100%, 95%, 83%, 64%, and 33% for PASI 100, PASI 90-99, PASI 75-89, PASI 50-74, and PASI <50, respectively). Among patients achieving PASI >50 at week 28 and continued up to 52 weeks, % PASI improvement remained consistent or improved from week 28 to week 52. Similar results were observed for TIL 200 mg as well as subgroup analysis with bio-naive and bio-experienced patients, respectively. Conclusion(s): The majority of TIL 100 and 200 mg patients achieved PASI >50 response at week 28, and PASI improvement was maintained from week 28 to week 52. Among patients achieving >=PASI 90 at week 28, TIL 100 and 200 mg were associated with rapid improvement by week 4.Copyright © 2018