Eculizumab (Ecu), a terminal complement inhibitor, is the first approved treatment for aHUS. We report long-term follow-up data from a phase 2 trial in which pts with aHUS with a long disease duration and CKD were treated with Ecu.
Pts aged ≥12 yrs with aHUS and receiving chronic plasma exchange/plasma infusion (PE/PI) on a stable regimen were enrolled in an open-label, single-arm, phase 2 trial. PE/PI was discontinued and Ecu initiated (900 mg/wk for 4 wks, 1200 mg at wk 5, then 1200 mg q2 wks thereafter). Primary endpoints (26wks) were TMA event-free status (≥12 consecutive wks with no platelet count change >25% + no PE/PI + no new dialysis) and haematologic normalisation (platelet count ≥150´109/L and lactate dehydrogenase ≤ upper limit of normal sustained ≥4 weeks). Data were also collected up to 2 yrs of treatment in the extension study.
20 pts were enrolled in the 26-wk trial; 19 pts entered the long-term extension. TMA event‑free status was achieved in 16 pts (80%) at 26 wks and in 19 pts (95%) at a median follow-up of 114 wks. Haematologic normalisation was achieved in 18 pts (90%) by 26 wks and was maintained at a median of 114 weeks. At 26 wks haemoglobin (Hb) level and eGFR were significantly improved, and continued to improve during the extension period (Table). Mean platelet count ±SD was 228±77.66x109/L at baseline and did not significantly change during treatment. Ecu was well tolerated and AE rates remained steady or declined with longer duration of Ecu treatment.
Long-term treatment with Ecu in aHUS patients with long disease duration was associated with a sustained suppression of TMA, continued and significant improvement in renal function and was well tolerated. These results support the importance of ongoing Ecu treatment in these aHUS pts.