Iptacopan/LNP023 and rituximab as rescue therapy in a patient with systemic lupus erythematosus-associated atypical haemolytic uraemic syndrome.

Systemic lupus erythematosus (SLE) is rarely associated with atypical haemolytic uraemic syndrome, leading to a poor prognosis with multi-system involvement. The pathogenesis seems to be driven by hyperactivation of alternate pathways of complement cascade and patients should be treated with prompt administration of complement inhibitors and immunosuppressive therapy. Iptacopan/LNP023, a novel, orally administered C3 convertase inhibitor that has shown efficacy in C3 glomerulopathy and paroxysmal nocturnal haemoglobinuria, is going to be tested in patients with atypical haemolytic syndrome. We present a case of a 59 year-old patient with mild systemic lupus erythematosus developing atypical haemolytic uraemic syndrome with renal, myocardial and neurological involvement, which was refractory to synthetic immunosuppressive, eculizumab and plasma exchange therapies. The syndrome rapidly subsided after iptacopan/LPN023 administration associated with a single rituximab cycle, followed by tapering of glucocorticoids, immunosuppressive therapy and plasma exchange. Unfortunately, kidney failure occurred requiring twice weekly haemodialysis sessions. To the best of our knowledge, this is the first case of SLE-aHUS successfully treated with iptacopan/LPN023, in association with standard SLE immunosuppression.