Efficacy of Tildrakizumab Across Different Body Weights in Moderate-to-Severe Psoriasis Over 5 Years: Pooled Analyses from the reSURFACE Pivotal Studies

Abstract

Introduction: Tildrakizumab (TIL), a monoclonal antibody that selectively targets interleukin-23p19, has been approved for the treatment of moderate-to-severe plaque psoriasis. According to the European Medicines Agency Summary of Product Characteristics, the recommended dose is 100 mg, but a 200 mg dose can be used in patients with certain characteristics, such as a high disease burden or body weight (BW) ≥ 90 kg. Fixed one-dose biological therapies tend to become less effective in patients with high BW. This post-hoc study describes the long-term efficacy of TIL across different BWs in pivotal clinical trials.

Methods: A 5-year pooled analysis of two double-blind, randomised, controlled phase III trials-reSURFACE 1 and 2-was performed. Efficacy measures were the proportions of the patients with an absolute Psoriasis Area and Severity Index (PASI) of < 3 and < 1 and a Dermatology Life Quality Index (DLQI) of 0/1. The study population included patients randomised to TIL 100 mg or TIL 200 mg who received ≥ 1 TIL dose up to week 12 (part 1 of the trial) or up to week 28 (part 2) and patients who were responders (≥ 75% improvement in PASI) to TIL 100 or TIL 200 mg at week 28 and who were maintained on the same dose up to week 244. Efficacy was evaluated by analysing BW subgroups at weeks 28, 52 and 244. Missing data were analysed using multiple imputation. Safety was assessed in the all-patients-as-treated population.

Results: The proportions of TIL-treated patients with PASI < 3 and < 1 (up to week 244) and DLQI 0/1 (up to week 52) were similar for patients with BW < 90 or ≥ 90 kg, regardless of dose. Patients ≥ 120 kg had greater efficacy outcomes at the 200 mg dose. Safety outcomes were similar regardless of treatment dose and weight (< 120/≥ 120 kg).

Conclusion: In patients with BW ≥ 120 kg, TIL 200 mg is more efficacious than TIL 100 mg, with similar favourable safety profiles obtained regardless of dose and BW group.

Trial registration: ClinicalTrials.gov NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).

Keywords: Body weight; DLQI; PASI; Psoriasis; Tildrakizumab.

© 2022. The Author(s).

Figures

Fig. 1

Study design. White letters represent differences between the reSURFACE 1 and reSURFACE 2 trials. The sample assessed for efficacy in this study is shown in red. D/C discontinued, NR non-responder (< 50% improvement in PASI), PASI Psoriasis Area and Severity Index, PR partial responder (50–75% improvement in PASI), R responder (≥ 75% improvement in PASI), TIL tildrakizumab

Fig. 2

PASI  vertical lines on the bars represent 95% confidence intervals. These analyses were performed using a multiple imputation approach. BW body weight, PASI Psoriasis Area and Severity Index, TIL tildrakizumab

Fig. 3

PASI  vertical lines on the bars represent the 95% confidence intervals. These analyses were performed using a multiple imputation approach. BW body weight, PASI Psoriasis Area and Severity Index

Fig. 4

PASI vertical lines on the bars represent the 95% confidence intervals. These analyses were performed using a multiple imputation approach. BW body weight, PASI Psoriasis Area and Severity Index

Fig. 5

DLQI 0/1 responders over time by BW group and TIL dose. The vertical lines on the bars represent the 95% confidence intervals. These analyses were performed using a multiple imputation approach. BW body weight, DLQI Dermatology Life Quality Index, TIL tildrakizumab

Fig. 6

Sensitivity analysis: correlation between BW and the absolute PASI change from baseline at week 28. BW body weight, PASI Psoriasis Area and Severity Index

Fig. 7

Sensitivity analysis: correlation between BW and the absolute DLQI change from baseline at week 28. BW body weight, DLQI Dermatology Life Quality Index