Dose Reduction of IL17 and IL23 Inhibitors in Psoriasis (BeNeBio study): An International, Pragmatic, Multicentre, Randomised, Controlled, Non-Inferiority Trial.

内容摘要

Interleukin (IL)17 and IL23 inhibitors (i) for psoriasis are highly effective but not all patients may need the registered dose. Dose reduction (DR) could contribute to prevent unnecessary drug exposure and lower healthcare expenditures. The aim of this study was to evaluate whether DR through stepwise interval prolongation is effective and safe in patients with psoriasis with stable low disease activity. This pragmatic, open-label, controlled, non-inferiority randomised clinical trial was performed in 19 (non-)academic hospitals in the Netherlands and Belgium. Patients were randomised (2:1) to stepwise DR or usual care (UC) by block randomisation with random allocation sequence, stratified by biologic. Patients with stable low disease activity on registered dosages of IL17i (secukinumab, ixekizumab, bimekizumab, brodalumab) or IL23i (guselkumab, risankizumab, tildrakizumab) were eligible. In DR, injection intervals were prolonged stepwise to 67.0% and 50.0% of the original dose if disease activity permitted. The primary aim was to assess non-inferiority of this DR strategy compared to UC regarding the incidence proportion of persistent flares (Psoriasis Area and Severity Index (PASI) > 5 for ≥3 months) after 18 months, with a non-inferiority margin of 15.0%. Patients were analysed by intention-to-treat (ITT) and per-protocol (PP) with imputation of missings. ClinicalTrials.gov Identifier NCT04340076; status: closed. Between June 30, 2020 and September 14, 2023, 244 patients were included (mean age 51 ± 15 years; 67.0% male; DR N = 164, UC N = 80). After 18 months, a difference of 2.4% (95% CI -2.0% to 6.8%) in incidence proportion of persistent flares (DR (4.0%) and UC (1.6%) in ITT) showed non-inferiority of DR. No serious adverse events/deaths related to DR were reported. Disease-activity guided, stepwise interval prolongation of IL17i and IL23i in patients with controlled psoriasis is an effective and safe strategy to reduce unnecessary exposure to these expensive drugs. ZonMw (the Netherlands Organization for Health Research and Development), KCE Trials (the Belgian Health Care Knowledge Centre).