MO020EFFICACY AND SAFETY OF THE LONG-ACTING C5 INHIBITOR RAVULIZUMAB IN PATIENTS WITH POSTPARTUM ATYPICAL HAEMOLYTIC URAEMIC SYNDROME

Abstract

Background and Aims Atypical haemolytic uraemic syndrome (aHUS) triggered by pregnancy is a rare and under-recognised disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor built on eculizumab, with a maintenance dosing interval of 8 weeks, is efficacious in treating aHUS. In this analysis, we report outcomes in a subgroup of patients with postpartum-aHUS enrolled in the 311 study. Method This was a global, phase 3, single-arm, multicentre trial evaluating the efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete thrombotic microangiopathy (TMA) response (simultaneous platelet count normalisation [≥150 x 109/L], lactate dehydrogenase [LDH] normalisation [≤246 U/L] and ≥25% improvement in serum creatinine at 2 separate assessments ≥28 days apart) through the 183-day initial evaluation period. Additional efficacy endpoints were: time to complete TMA response, haematological normalisation (platelet count and LDH), dialysis requirement status, and change in eGFR. Results Eight patients with postpartum-aHUS (mean age 36 [±8] years) were diagnosed within 12 days of delivery. Seven patients were white and one was Asian. Six patients (75%) had received plasma exchange/infusion before ravulizumab therapy; five (63%) were on dialysis. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 32 days. Haematological normalisation was observed in all patients. By Day 29, all five patients on dialysis at baseline had discontinued dialysis, and by Day 183 all eight patients had improved CKD stage (defined based on eGFR value) by ≥1 category. Three possible treatment-related adverse events (non-serious) were noted in two patients (arthralgia and nasopharyngitis; urinary tract infection). All patients survived and no meningococcal infections occurred. Conclusion This is the first prospective analysis of a C5 inhibitor in postpartum-aHUS. Treatment with ravulizumab resulted in rapidly improved haematological and renal outcomes with no unexpected adverse events identified when administered at 8-weekly dosing intervals through intravenous infusion.