ACR/ARP 2019

Abstract

Anifrolumab, a human monoclonal antibody targeting the type I IFN receptor subunit 1, is beneficial for patients with moderate to severe systemic lupus erythematosus (SLE) who have active disease despite receiving standard therapy. Richard Furie (Northwell Health, USA) and Eric Morand (Monash University, Australia) presented findings from two phase 3 trials in SLE. In TULIP-1, patients were randomly assigned (2:1:2) to receive placebo (n=184), anifrolumab 150 mg (n=93), or anifrolumab 300 mg (n=180) intravenously every 4 weeks for 48 weeks. In TULIP-2, patients were randomly assigned (1:1) to receive either placebo (n=182) or anifrolumab 300 mg (n=180) on the same schedule. In both trials, standard-of-care treatment continued except for oral corticosteroid tapering for patients receiving 10 mg/day or more prednisone or equivalent at baseline. TULIP-1 did not meet its primary endpoint (SLE responder index-4 at week 52), with 65 (36%) of 180 patients in the 300 mg anifrolumab group achieving SRI-4 versus 74 (40%) of 184 in the placebo group. However, more patients in the anifrolumab group achieved a reduction in oral corticosteroid dose and a BILAG-based composite lupus assessment (BICLA) response, suggesting potential clinical benefit of the drug. In TULIP-2, anifrolumab was superior to placebo for BICLA response at week 52 (the primary endpoint), with 86 (48%) of 180 patients in the anifrolumab group and 57 (31%) of 182 in the placebo group achieving BICLA response. The safety profile of anifrolumab's safety was similar to that observed in phase 2 trials. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trialThe primary endpoint was not reached. However, several secondary endpoints, including reduction in oral corticosteroid dose, CLASI responses, and BICLA responses, suggest clinical benefit of anifrolumab compared with placebo. Conclusive evidence for the efficacy of anifrolumab awaits further phase 3 trial data. Despite the inherent limitations of a 1-year phase 3 study, such as incomplete knowledge of applicability to the general population and scarce detection of rare safety signals, in addition to complications from prespecified restricted medication rules, our results suggest that anifrolumab might have the potential to provide a treatment option for patients who have active SLE while receiving standard therapy. Full-Text PDF