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) C 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 C 1 TIL dose up to week 12 (part 1 of the trial) or up to week 28 (part 2) and patients who were responders (C 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 C 90 kg, regardless of dose. Patients C 120 kg had greater efficacy outcomes at the 200 mg dose. Safety outcomes were similar regardless of treatment dose and weight (\ 120/C 120 kg). Conclusion: In patients with BW C 120 kg, TIL 200 mg is more efficacious than TIL 100 mg,

Effectiveness and safety of tildrakizumab for the treatment of psoriasis in real‐world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group

“…Conversely, other studies have suggested that tildrakizumab response was not modified by prior BT expossure 12,17,18 . In line with our findings, most RWE studies suggest that effectiveness was not influenced by BMI, 11–13,16 although a pooled analysis form reSURFACE 1/2 pointed to the opposite direction 22,23 . To date, RWE studies have not reported a negative impact of psoriatic arthritis history in tildrakizumab effectiveness 16,17 …”

“…12,17,18 In line with our findings, most RWE studies suggest that effectiveness was not influenced by BMI, [11][12][13]16 although a pooled analysis form re-SURFACE 1/2 pointed to the opposite direction. 22,23 To date, RWE studies have not reported a negative impact of psoriatic arthritis history in tildrakizumab effectiveness. 16,17 Though not included in the SmPC, off-label reduced dose regimens are sometimes used in clinical practice.…”

Tildrakizumab for the Treatment of Moderate-to-Severe Psoriasis: Results from 52 Weeks Real-Life Retrospective Study

“…Interestingly, no significant differences were reported in terms of PASI response rates, and adverse events up to week 244 between patients with and without metabolic syndrome, confirming tildrakizumab efficacy and favorable safety profile even in long-term follow-up also in patients with metabolic syndrome. 29 ReSURFACE studies also showed tildrakizumab as a safe treatment in moderate-to-severe psoriasis. 23,28 Indeed, tildrakizumab, at both 100 and 200 mg dosages, did not raise any safety issues in both reSURFACE trials, resulting comparable to placebo in terms of reported AEs.…”

Safety of IL-23 p19 Inhibitors for the Treatment of Patients With Moderate-to-Severe Plaque Psoriasis: A Narrative Review

“…In post hoc analyses of reSURFACE 1 and reSURFACE 2 data, the long-term (5 years) safety profile of tildrakizumab was similar regardless of body weight [ 62 ] or presence of metabolic syndrome (Table 5 ) [ 63 ]. Five-year rates of AEs and AEs of interest during treatment with tildrakizumab 100 mg and 200 mg were similar between patients with psoriasis weighing < 120 kg and those weighing ≥ 120 kg [ 62 ].…”

“…In post hoc analyses of reSURFACE 1 and reSURFACE 2 data, the long-term (5 years) safety profile of tildrakizumab was similar regardless of body weight [ 62 ] or presence of metabolic syndrome (Table 5 ) [ 63 ]. Five-year rates of AEs and AEs of interest during treatment with tildrakizumab 100 mg and 200 mg were similar between patients with psoriasis weighing < 120 kg and those weighing ≥ 120 kg [ 62 ]. The combined rates (patients with events) of AEs of special interest (drug hypersensitivity, serious infections, malignancies, melanoma, NMSC, MACE, and injection site reactions) for patients without and with metabolic syndrome, respectively, were 2.1 and 2.0 for tildrakizumab 100 mg and 2.6 and 5.2 for tildrakizumab 200 mg [ 63 ].…”