33124 Severe infections, confirmed extended major adverse cardiovascular events, and malignancies over 5 years of treatment with tildrakizumab in terms of number needed to harm: Pooled analyses from the reSURFACE 1 and reSURFACE 2 phase 3 trials

Abstract

Background: Tildrakizumab, a high-affinity anti–interleukin 23p19 monoclonal antibody approved for moderate to severe plaque psoriasis, has demonstrated efficacy and safety up to 5 years. Here, we evaluated number needed to harm (NNH) for treatment with tildrakizumab 100 and 200 mg for severe infections, confirmed extended major adverse cardiovascular events (MACE), or malignancy (excluding nonmelanoma skin cancer [NMSC]) through 5 years in the reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) phase 3 trials. Methods: Methodology for the randomized controlled trials reSURFACE 1 (64 weeks [W]) and reSURFACE 2 (52W) is published. After the base study, select patients entered an optional 4-year extension up to W256 (reSURFACE 1)/W244 (reSURFACE 2). Pooled safety data were included. Malignancies reported excluded NMSC. NNH was calculated as 1/(patients with event/patients treated with tildrakizumab 100 or 200 mg) regardless of causality, including baseline risks of severe infection, MACE, and malignancy, which are higher in psoriasis patients compared with the general population. Results: Overall, 872 and 928 patients receiving tildrakizumab 100 and 200 mg, respectively, were included. For tildrakizumab 100/200 mg, the NNH for a severe infection, MACE, or malignancy (any preferred term) to occur within 5 years was 23.0/20.6, 58.1/42.2, or 41.5/54.6 patients, respectively. The most commonly reported severe events included cellulitis, diverticulitis, and pneumonia (infections); acute myocardial infarction and coronary artery disease (confirmed extended MACE); and malignant melanoma in situ and rectal adenocarcinoma (malignancies). Conclusions: Tildrakizumab demonstrated a favorable safety profile, with high NNH for severe infections, confirmed extended MACE, and malignancies over 5 years.