A systematic review of the role of eculizumab in systemic lupus erythematosus-associated thrombotic microangiopathy

Abstract

Background: Lupus nephritis (LN) is a severe consequence of systemic lupus erythematosus (SLE) that affects approximately 40% of patients. Pathogenic immune complexes that are characteristic of LN deposit in the kidney and activate immune mediated pathways including the complement system. Complete remission rates in LN are approximately 44% highlighting the need for new treatment strategies in these patients. Eculizumab is a fully humanised IgG2/IgG4 monoclonal antibody directed at C5 and thus prevents the formation of the terminal complement complex. Eculizumab is successfully used in atypical haemolytic uraemic syndrome (aHUS) and paroxysomal nocturnal haemoglobinuria (PNH) but it is not standardly used in LN. The aim of this project was to determine whether there is any role for eculizumab as adjunctive therapy in LN. Methods: Using a predefined search strategy on Ovid MEDLINE and EMBASE the literature was reviewed systematically to identify studies in which eculizumab had been used to treat patients with SLE. All patients were included that were treated with complement inhibitors. Favourable outcome in this study was defined as resolution of symptoms that led to treatment, discharge from hospital or recovery of renal function. Patients were excluded if there was no outcome data or if complement inhibition was unrelated to their SLE. Results: From 192 abstracts screened, 14 articles were identified, involving 30 patients. All SLE patients administered eculizumab were treated for thrombotic microangiopathy (TMA) secondary to LN diagnosed either histologically (66%) or as part of a diagnosis of aHUS (73%). 93% of patients had a favourable outcome in response to eculizumab treatment, of which 46% had a favourable outcome and successfully stopped treatment without relapse in symptoms during a median follow up of 7 months. Three patients (10%) reported adverse outcomes related to eculizumab therapy.

A Review of Complement Activation in SLE

“…A majority (28/30) of the patients had resolution of symptoms and recovery of renal function or were able to be discharged from the hospital. This underscores the interest in the development of complement inhibitory medications and the need for markers to determine which patients will benefit the most from them [ 34 •].…”

The Use of Glucocorticoids in Lupus Nephritis: New Pathways for an Old Drug

“…Targeting the activated complement system with complement inhibitors may also promote GC-reduced or GC-free regimens. Although complement inhibition in lupus nephritis has been used in a few case reports ( 96 , 97 ), particularly in the context of concomitant thrombotic microangiopathy, the CLEAR ( 98 ) and ADVOCATE ( 99 ) studies in ANCA-associated vasculitis suggest this may be an approach worth investigating in lupus nephritis. In these studies, administration of avacopan (an oral complement C5aR inhibitor) along with cyclophosphamide or rituximab, allowed the administration of a GC-free regimen with higher remission rates at 52 weeks of follow-up in patients with ANCA-associated vasculitis ( 99 ).…”

Eculizumab therapy on a patient with co‐existent lupus nephritis and C3 mutation‐related atypical haemolytic uremic syndrome: a case report

“…Recently, a case series has shown that eculizumab results to favourable outcomes in patients with aHUS and SLE [ 7 , 11 , 16 ]. Eculizumab led to improvement of symptoms, thrombocytopaenia, kidney function, and proteinuria in patients who were refractory to conventional immunosuppressive treatment and plasmapheresis [ 17 ].…”