Efficacy of Eculizumab Discontinuation in Atypical Hemolytic Uremic Syndrome: A Systematic Review and Meta-analysis Open Access

Atypical hemolytic uremic syndrome (aHUS), a life-threatening complement-mediated disorder, is now treatable with terminal complement inhibitors like eculizumab. Although effective, these therapies are costly and increase susceptibility to infections, notably meningococcal disease, raising concerns about long-term use. The optimal duration of complement inhibition remains unclear, prompting efforts to explore the possibility of treatment discontinuation. We conducted a systematic review and meta-analysis to evaluate the benefits and risks of stopping terminal complement inhibitor therapy in aHUS. We searched PubMed, Scopus, and CINAHL for studies of continuing vs. stopping anti-complement treatment in aHUS. Of 3303 identified studies, 13 observational studies (3 case-control, 10 cohort) comprising 584 patients were included. Overall, continuing treatment was associated with an approximately 76% reduction in the odds of relapse (odds ratio [OR] 0.24, 95% CI: 0.09 to 0.62; p= 0.01.) Study design influenced results: cohort studies showed a more modest effect (OR=0.40 (95% CI: 0.15 to 1.09), while case-control studies reported inflated estimates (OR=0.04 (95%CI: 0.02 to 0.08); subgroup interaction p=0.03). Patients with various genetic variants [CFH, CFHdel, MCP] had decreased relapse with continued therapy when case-control studies were included in the analysis. When the analysis was restricted to cohort studies, the effects became uncertain [statistically non-significant with large confidence intervals]. While current evidence is insufficient to provide personalized guidance on which patients with aHUS can safely discontinue anti-complement therapy, findings from higher-quality studies-which show no statistical difference between continued and discontinued treatment-suggest that discontinuation may be possible for at least some patients.