Complement‐mediated thrombotic microangiopathy treated with anticomplement protein 5 therapy, a retrospective study

Abstract Background Complement‐mediated thrombotic microangiopathy (CM‐TMA), also called atypical hemolytic uremic syndrome (aHUS), is a difficult‐to‐diagnose rare disease that carries severe morbidity and mortality. Anti‐C5 monoclonal antibodies (aC5‐mab) are standard treatments, but large studies and long‐term data are scarce. Here, we report our single institution experience to augment the knowledge of CM‐TMA treated with aC5‐mab therapy. Methods We aimed to assess the short and long‐term effects of aC5‐mab in patients diagnosed with CM‐TMA treated outside of a clinical trial. This was a retrospective study. We included all patients diagnosed with CM‐TMA and treated with aC5‐mab at our institution. There were no exclusion criteria. Endpoints included complete TMA response (CR) defined as normalization of hematological parameters and ≥25% improvement in serum creatinine (Cr) from baseline in patients with renal disease, relapse defined as losing the previously achieved CR, morbidity, adverse events, and survival. Results We found 28 patients with CM‐TMA treated with aC5‐mab. The median age was 50 years. Baseline laboratories: platelet counts 93 × 10 9 /L, hemoglobin 8.6 g/dL, lactate dehydrogenase 1326 U/L, serum Cr 4.7 mg/dL, and estimated glomerular filtration rate 19 mL/min. One individual was on renal replacement therapy (RRT) and 10 initiated RRT within 5 days of the first dose of aC5‐mab. Genetic variants associated with CM‐TMA included mutations in C3, CFB, CFH, CFHR1/3, CFI, and MCP. The mean duration of hospitalization was 24 days. The median time to initiation of aC5‐mab was 10 days. Sixteen subjects received RRT. At the time of hospital discharge, 27 were alive, 14 remained on RRT, and 4 had a CR. At 6 months, 23 patients were alive, 18 continued aC5‐mab, 8 remained on RRT, and 9 had a CR. At the last follow‐up visit past 6 months, 20 were alive, 14 continued aC5‐mab, 5 remained on RRT, 12 had a CR, and 1 was lost to follow‐up. Conclusions Our study provides real‐world experience and insight into the long‐term outcomes of CM‐TMA treated with aC5‐mab. Our findings validate that CM‐TMA is an aggressive disease with significant morbidity and mortality, and confirm that aC5‐mab is a relatively effective therapy for CM‐TMA. Our study adds practical, real‐world experience to the literature, but future research remains imperative.