Safety profile of concizumab: A systematic review and meta-analysis of randomised controlled trials

Introduction Haemophilia, a genetic bleeding disorder caused by deficiencies in clotting factors VIII (haemophilia A) or IX (haemophilia B), impairs coagulation, requiring frequent intravenous clotting factor infusions. Concizumab, a subcutaneous monoclonal antibody targeting tissue factor pathway inhibitor (TFPI), offers a potential alternative for prophylactic treatment. Objective This meta-analysis evaluates the safety of concizumab in people with haemophilia, focusing on adverse events, serious adverse events, upper respiratory tract infections, and joint bleeding episodes. Methodology A systematic search of PubMed, Cochrane Library, Scopus, Google Scholar, and ClinicalTrials.gov (up to February 15, 2025) identified randomised controlled trials comparing concizumab with placebo or standard therapy. Risk ratios (RR) with 95% confidence intervals (CI) were calculated, and heterogeneity was assessed using the I 2 statistic. Results Four studies (137 participants) met inclusion criteria. Concizumab showed a non-significant increase in overall adverse events (RR = 1.17; 95% CI: 0.89–1.54). Serious adverse events were lower in the concizumab group (RR = 0.46; 95% CI: 0.06–3.53) but not statistically significant. Upper respiratory tract infections were similar (RR = 0.75; 95% CI: 0.15–3.85). Joint bleeding was slightly reduced (RR = 0.66; 95% CI: 0.45–0.96). Conclusion Concizumab appeared generally well tolerated in short-term randomised trials. The current evidence base is small and lacks long-term or real-world data; therefore, the comparative safety of concizumab relative to standard therapies remains uncertain. Given the challenges of conducting large randomised trials in rare diseases, long-term registry-based follow-up may provide the most feasible and informative data on concizumab's safety and efficacy.