Discussion

Eculizumab is an excellent drug for treating aHUS, with an overall favorable risk profile [1, 2]. However, several issues remain to be addressed with respect to life-long treatment. There are no firmly established guidelines for treatment duration in patients with aHUS, and we are attempting to establish less aggressive dosing schedules, or to even completely discontinue treatment. Various markers to help guide this decision are being sought, but none has yet been established as an ideal one. Among the possible justifications for its withdrawal are the risk of potentially serious meningococcal infections and rare immune-mediated drug reactions [2, 3, 4]. The fact that it is an intravenous twice-monthly dosing drug, and an extremely expensive one, can make life-long therapy very inconvenient. For this reason, a patient request and economic considerations for its withdrawal have also been cited [1, 2, 5]. On the other hand, there are also several issues that speak against eculizumab withdrawal. The risk of relapse in patients with aHUS who discontinued eculizumab, including evidence from case reports, unpublished cases, and national registries, ranged from 20 to 66%[6]. Children represent a highrisk group in that common events leading to complement activation, such as infection or vaccination, are frequent in this age group. Pediatric guidelines therefore state that the withdrawal of eculizumab should not be considered in children with life-threatening symptoms upon presentation or those who have not fully recovered renal function [7]. It is not very clear whether the presence of a genetic mutation is an important risk factor for relapse or not. It was found to be important for relapse in French aHUS registry data [8], while this was not the case in the aggregate data from prospective trials of eculizumab including 61 patients, where the