Efficacy and safety of biologic drugs in Still's disease: a systematic review and network meta-analysis of randomized controlled trials

Abstract Objectives Still’s disease is a rare autoinflammatory disorder characterized by systemic inflammation, fever, rash and arthritis. The term ‘Still’s disease’ covers the paediatric subtype systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD), which affects adults. Biologic drugs, including the anti-IL-1 agents anakinra, canakinumab and rilonacept and the IL-6 antagonist tocilizumab, are used in the management of Still’s disease. Methods We conducted a systematic review and network meta-analysis of randomized controlled trials, and the study protocol was registered in PROSPERO (CRD42023450442). MEDLINE, EMBASE and CENTRAL were screened from inception until 17 September 2023. We included patients with Still’s disease who received placebo or biologic drugs: anakinra, canakinumab, rilonacept or tocilizumab. The primary efficacy and safety outcomes were achievement of ACR50 response and occurrence of serious adverse events, respectively. The interventions were ranked using rankograms and SUCRA values. Results Nine trials with 430 patients were included. All biologic drugs were associated with greater odds of ACR50 response compared with placebo. There was no statistically significant association between biologic drugs and serious adverse events. The multivariate meta-analysis found no difference between biologic drugs. As per SUCRA rankings, anakinra was the most effective and safe option with respect to ACR50 response and occurrence of serious adverse events. Conclusion This is the first systematic review and meta-analysis to assess the efficacy and safety of biologic drugs in paediatric and adult patients with Still’s disease. Biologic drugs were effective in achieving ACR response and demonstrated a low adverse event profile in the management of Still’s disease.