#550 Characteristics of patients with aHUS who discontinued dialysis after eculizumab treatment: sub-analysis of post-marketing surveillance in Japan
Authors: Ito Shuichi , Matsumoto Masanori , Shimono Akihiko , Teranishi Hirofumi , Maruyama Shoichi 
Published: May 2024

Abstract

Background and Aims
Atypical haemolytic uraemic syndrome (aHUS), a type of thrombotic microangiopathy (TMA), is a disease accompanied by acute kidney injury which typically requires dialysis in half of the patients. Eculizumab is the first complement C5 inhibitor approved for aHUS in Japan. Early treatment initiation with eculizumab is associated with better renal outcomes, and dialysis withdrawal has been observed in some of patients on dialysis after treatment with eculizumab. However, patient characteristics relating to dialysis continuation or withdrawal after treatment with C5 inhibitors have not been investigated.

Method
Paediatric and adult patients with aHUS who were enrolled in Japanese post-marketing surveillance (PMS) for eculizumab and who were on dialysis at the initiation of eculizumab treatment were included in this analysis. Characteristics and clinical courses were compared in two groups: patients who discontinued dialysis within 26 weeks from initiation of eculizumab (Group A) and those who stayed on dialysis for 26 weeks (Group B).

Results
Among 38 patients included in this analysis, 21 patients (55%) discontinued dialysis (Group A) and 17 patients (45%) stayed on dialysis (Group B). The proportion of paediatrics/adults (7/14 vs. 2/15, P = 0.148), median age (6 vs. 8 years old, P = 0.88 and 54.5 vs. 62 years old, P = 0.47), and the proportion of patients with/without complement-related gene variants or anti-CFH antibody (9/8 vs. 6/5, P = 1.000) were comparable between the two groups. Meanwhile, the proportion of patients with hypertension at baseline was significantly lower in Group A than in Group B (6/21 vs. 11/17, P = 0.022). The median duration of dialysis before initiation of eculizumab (6.0 days vs. 17.0 days, P = 0.011) and the median time from TMA onset to eculizumab initiation (9.0 days vs. 25.0 days, P = 0.008) were significantly shorter in Group A than in Group B, respectively. In contrast, there was no significant difference in the median time from TMA onset to initiation of plasma therapy between the two groups (3.5 days vs. 8.0 days, P = 0.154). No significant difference was also observed in the median (range) duration of eculizumab treatment [75 (13-241) weeks vs. 40 (12-256) weeks, P = 0.167]. Stepwise multivariate logistic regression analysis showed that the time from TMA onset to eculizumab initiation (&lt;15 days/≥15 days) was an independent factor associated with the withdrawal of dialysis (P = 0.013), but the existence of hypertension at baseline as a complication and patients age (paediatrics/adults) were not (P = 0.157 and P = 0.869). No patients in Group A restarted dialysis after dialysis discontinuation. Five out of 17 patients in Group B discontinued dialysis after 27 weeks; their median (range) time to dialysis withdrawal was 63 (27-184) weeks.

Conclusion
These results demonstrate that early initiation of C5 inhibitors can offer the chance of renal recovery and no further need for dialysis. Continuing treatment with C5 inhibitor beyond 26 weeks may also offer the chance to discontinue dialysis for some patients.