Efficacy and safety of medications for antihistamine-refractory chronic spontaneous urticaria: a systematic review and network meta-analysis

Abstract

Summary Purpose Most medications for antihistamine-refractory chronic spontaneous urticaria (CSU) have not been compared head-to-head. This systematic review and network meta-analysis evaluates their relative efficacy and safety. Methods Electronic databases were searched until 05 May 2022 for randomized controlled trials investigating systemic medications for antihistamine-refractory CSU. The change in the urticaria activity score over seven days (UAS7) and occurrence of adverse events were compared between treatments using random-effects network meta-analysis models. Results In all, 32 studies with 3641 patients receiving 31 different systemic medical interventions were included. Among currently available drugs, omalizumab 300 mg injected every 4 weeks and cyclosporine 3–5 mg/kg daily per os were most effective in reducing the UAS7 with a reduction of −10.45 (95% confidence interval [CI]: −12.35, −8.55) and of −10.40 (95% CI: −19.4, −1.4) compared to placebo. Similar efficacies were shown by the nonapproved agents ligelizumab 72 mg injected every 4 weeks (−11.67, 95% CI: −16.80, −7.15) and fenebrutinib 400 mg daily per os (−9.50, 95% CI: −17.56, −1.44). The odds ratio for the occurrence of an adverse event with placebo as comparator was 1.09 for omalizumab (95% CI: 0.83, 1.42), 2.16 for cyclosporine (95% CI: 0.77, 6.07: GRADE; moderate certainty), 0.89 for ligelizumab (95% CI: 0.47, 1.69), and 2.14 for fenebrutinib (95% CI: 0.62, 7.38) in the mentioned dosages. Conclusion Omalizumab 300 mg injected every 4 weeks and cyclosporine 3–5 mg/kg daily per os are the most effective currently available drugs for antihistamine-refractory CSU. Cyclosporine shows a relatively less favorable safety profile.