Five‐year efficacy and safety of tildrakizumab in patients with moderate‐to‐severe psoriasis who respond at week 28: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2)*

Abstract

Summary Background The phase III reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) trials of the anti‐interleukin‐23p19 monoclonal antibody tildrakizumab (TIL) for psoriasis treatment are complete. Objectives We present 5‐year pooled data from reSURFACE 1 and reSURFACE 2. Methods reSURFACE 1 and reSURFACE 2 were double‐blind, randomized, controlled studies with optional long‐term extensions. Adults with moderate‐to‐severe chronic plaque psoriasis were randomized 2 : 2 : 1 to TIL 100 mg (TIL 100) or 200 mg (TIL 200) or placebo at weeks 0 and 4, and every 12 weeks thereafter [reSURFACE 2 included an etanercept (ETN) arm]. Efficacy outcomes included proportions of patients achieving absolute and relative improvement from baseline Psoriasis Area and Severity Index (PASI) score through week 244 in TIL responders (≥ 75% improvement from baseline PASI; PASI 75 response) continuously receiving the same dose and ETN partial responders and nonresponders (PASI < 75 response) switched to TIL 200 at week 28. Safety was assessed from adverse events (AEs) in all patients as treated. Results Efficacy analyses included 329 and 227 week 28 responders to TIL 100 and TIL 200, respectively, and 121 ETN partial responders/nonresponders switched to TIL 200 at week 28. Of TIL 100 or TIL 200 responders and ETN partial responders/nonresponders entering the extensions, 235/302, 176/213 and 85/107, respectively, were evaluated at week 244, and 88·7%, 92·5% and 81·3%, respectively, achieved PASI 75 response. Exposure‐adjusted rates of serious AEs were 6·3 and 6·0 patients with events per 100 patient‐years of TIL 100 and TIL 200, respectively. Conclusions TIL treatment provided sustained disease control over 5 years in week 28 TIL responders and ETN partial responders/nonresponders, with a reassuring safety profile.

Low incidence rate of respiratory and viral infections over 5 years of treatment with tildrakizumab in patients with moderate‐to‐severe psoriasis: pooled analysis from reSURFACE 1 and reSURFACE 2 phase 3 trials

“…Intriguingly, this phenomenon was observed primarily in Moderna vaccine but rarely reported in BNT162b2 COVID-19 vaccine by Pfizer-BioNTech. [2][3][4] Because the reports were limited to mRNA vaccines, a delayed-type hypersensitivity reaction to the excipient polyethylene glycol (PEG) in both mRNA vaccines was suggested as one potential aetiology. 4,5 Unlikely these mRNA vaccines, ChAdOx1 nCoV-19 (AZD1222) is a replication-defective chimpanzee adenovirus-vectored vaccine, and it includes polysorbate 80 as an excipient.…”

A Review of the Efficacy and Safety for Biologic Agents Targeting IL-23 in Treating Psoriasis With the Focus on Tildrakizumab

“…Recently the data became available highlighting 5-year efficacy and safety outcome based on long-term extension of the reSURFACE 1 and 2 trails ( 105 ). The results highlighted that patients who responded to tildrakizumab (i.e., achieved PASI 75 at week 28) 100 mg treatment demonstrated PASI 75/90/100 response at week 244 at the rate of 88.7, 65.9, and 32.8%, respectively.…”

“…Five-year analysis of safety data was comparable to findings of shorter time studies, where the most frequent treatment related AE was nasopharyngitis. Several severe AEs were observed in both tildrakizumab 100 mg and 200 mg groups and were deemed not related to treatment ( 105 ). Hence, long-term continuous dosing or switching from another biologic agent could be part of the psoriasis management regimen using tildrakizumab.…”

“…Furthermore, as mentioned above the long-term safety and tolerability of tildrakizumab has been evaluated using the data from tildrakizumab clinical trials for up to 244 weeks ( 105 ). Consistent with our review, frequencies of treatment-emergent AEs, serious AEs, discontinuations due to AEs, major adverse cardiovascular events, and severe infections were comparable between tildrakizumab 100 mg, tildrakizumab 200 mg, placebo, and etanercept groups in the reSURFACE 1 and 2 trials.…”

“…There were no AEs of inflammatory bowel disease or suicides reported up to 244 weeks of tildrakizumab use. Candida skin infections were infrequent with rates of 0.1, 0.3, 0.0, and 0.0% for the tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept groups, respectively ( 105 , 125 ).…”