Convincingly low levels of infections with long-term tildrakizumab

A post-hoc analysis of data from the reSURFACE 1 and 2 trials confirmed safety with low rates of drug-related infections of tildrakizumab treatment in patients with moderate-to-severe plaque psoriasis over 5 years.

Tildrakizumab is an IL-23 inhibitor that has previously demonstrated efficacy combined with favourable safety data for 3 years in patients with moderate-to-severe plaque psoriasis in phase 3 trials [1,2]. In these randomised, controlled studies, adults were treated with tildrakizumab 100 mg or 200 mg or placebo at weeks 0 and 4, and subsequently every 12 weeks. The reSURFACE 2 (NCT01729754) trial also included an arm with the active comparator etanercept [2]. After the base studies, patients eligible to enter the extension part of the trials were continued on tildrakizumab according to their response or previous study arm within the base trial. Hence, the extension included 506 patients of reSURFACE 1 (NCT01722331) and 730 of reSURFACE 2 [3].

As long-term safety is of major interest in chronic inflammatory diseases such as psoriasis, the new post-hoc analysis of the pivotal large reSURFACE 1 and 2 trials assessed rates of serious and drug-related infections over 5 years of drug exposure. To evaluate safety, all patients who received ≥1 dose in the extension phase of the same medication as in the base study were investigated for infections categorised as serious adverse events (SAE), as well as all infections. The analysed exposure to tildrakizumab equalled over 2,800 patient-years (PY) of 100 mg and over 2,900 PY of 200 mg. Mean age of the participants ranged from 44.2 to 47.1 in the different study arms, mean baseline Psoriasis Area Severity Index (PASI) score varied between 19.3 and 21.3.

The exposure-adjusted incidence rate for SAE infections in reSURFACE on both dosages of tildrakizumab was ≤1/100 PY, whereas exposure-adjusted incidence rate for serious drug-related infections was ≤0.3/100 PY. Most reported serious infections were diverticulitis, appendicitis, and gastroenteritis. Most frequently drug-related infections were nasopharyngitis, upper respiratory tract infections, and bronchitis; in reSURFACE 2 also rhinitis. In conclusion, no indications of new safety issues emerged and the exposure-adjusted incidence rate for drug-related infections over 5 years can be considered overall low and comparable between the 100 mg and 200 mg doses.

1. Reich, K, et al. Br J Dermatol. 2020;182(3):605–17.
2. Reich K, et al. Lancet. 2017;390:276–88.
3. Gebauer K, et al. Serious infections and infections related to study drug and leading to discontinuation through 5 years of tildrakizumab exposure in 2 phase 3 clinical trials. Poster 25363, AAD VMX 2021, 23-25 April.

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Posted on 7 June 202122 February 2024