MO316: Eculizumab for Adult Patients With Atypical Haemolytic-Uremic Syndrome: Full Dataset Analysis of Post-Marketing Surveillance in Japan

Abstract

Abstract BACKGROUND AND AIMS Atypical haemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) associated with dysregulation of the alternative complement pathway [1]. It is characterized by microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney injury [1]. In the USA, two adults per million develop aHUS each year, whereas 1 to 2 patients per million are estimated in Japan [2, 3]. Eculizumab has been approved for aHUS in Japan since 2013. A regulatory-mandated post-marketing surveillance (PMS) was conducted in a real-world setting from September 2013 to July 2018, for which an interim analysis has been published [3]. Here, we report the findings from the full data set analysis of the data from the PMS. METHOD The PMS enrolled adult patients diagnosed with aHUS and treated with at least one dose of eculizumab. The patients without underlying diseases, i.e. autoimmune diseases, drugs, infection, malignant tumours, metabolic disorders or transplantation, were evaluated for serious adverse events (SAE) and clinical effectiveness endpoints, i.e. haematologic normalization, platelet count (PLT) normalization, lactic dehydrogenase (LDH) normalization, a decrease of ≥ 25% in serum creatinine (sCr) levels, TMA event-free status and a complete TMA response (haematologic normalization and a ≥ 25% decrease in sCr that persisted for ≥ 4 weeks during eculizumab treatment). In addition, the difference of baseline (i.e. at treatment initiation of eculizumab) patient characteristics between patients who met and did not meet effectiveness endpoints was evaluated. RESULTS In this analysis, 79 adult patients were included; the median age was 54.0 years. Median eculizumab treatment duration was 30 weeks. The total exposure time of eculizumab was 75.51 person-years and 94 SAEs (1.24 per person-years) were reported in 39 patients. No unexpected safety signals were identified in this population by the end of observation. No meningococcal infection was reported throughout the observation period. Mean PLT (P < .001), LDH (P < .05) and estimated glomerular filtration rate (P < .01) were significantly improved after 7 days. Complete TMA response, haematologic normalization, PLT normalization, LDH normalization, improvement of sCr levels, and TMA event-free status were met by 35.3%, 40.4%, 49.2%, 50.0%, 51.3% and 50.0% of patients, respectively. Median treatment duration was shorter in patients who did not meet complete TMA response than in patients who met (6 weeks versus 114 weeks; P < .001). Multivariate analysis suggested that the time from most recent TMA to eculizumab treatment (OR 0.899; P = .007) and the days of plasma therapy (OR 0.807; P = .008) were negatively associated with improvement of sCr levels. CONCLUSION The percentages of patients who met effectiveness endpoints were similar to the interim analysis [3], yet the percentages of patients who met complete TMA responses were lower than in clinical trials [4]; the disparity in these outcomes could be attributed to the differences between clinical and real-world studies. This PMS analysis further demonstrated the safety and effectiveness of eculizumab in Japanese patients with aHUS in a real-world setting.