medwireNews: The first phase III trial of anifrolumab has failed to show a significant overall benefit for patients with systemic lupus erythematosus (SLE) when taken in addition to standard care, but does demonstrate some clinical response improvements that the researchers say deserve further investigation.
The primary endpoint of the study, presented at the 2019 ACR/ARP Annual Meeting in Atlanta, Georgia, USA and simultaneously published in The Lancet Rheumatology, was the proportion of patients achieving an SLE responder index (SRI)-4 response at 1 year.
This was achieved by 36% of the 180 patients randomly assigned to receive 300 mg infusions of anifrolumab, a monoclonal antibody that targets type I interferon alpha receptor subunit 1, every 4 weeks for 48 weeks and 40% of the 184 randomly assigned to receive placebo, a nonsignificant difference.
Anifrolumab was also not superior to placebo for those in the interferon gene signature test–high subgroup, either at week 24 or 52.
“However, several secondary endpoints, including BICLA response, sustained oral corticosteroid dose reduction, and organ-specific measures of skin and joint responses, suggest the possibility of clinical benefit of anifrolumab, although the statistical significance of these differences was not formally assessed,” note Richard Furie (Northwell Health, Great Neck, New York, USA) and co-researchers.
They add: “The optimal SLE trial design has not yet been established, and in a severe disease state with few approved treatments, detailed analyses of data from clinical trials with non-significant outcome results are essential.”
Indeed, BICLA response was achieved by 37% of anifrolumab-treated patients at 1 year, compared with 27% of those treated with placebo.
Furie and colleagues point out: “SRI-4 is based on the SLEDAI-2K, which requires complete resolution of a manifestation before that item’s score will change. Therefore, SRI-4 cannot capture partial resolution within an individual item, even if such improvement is clinically meaningful.
“By contrast, BICLA is based on improvements in BILAG-2004, which registers both graded and complete improvements within an organ domain and, therefore, is more sensitive.”
In a related commentary, Joan Merrill, from Oklahoma Medical Research Foundation in Oklahoma City, USA, says that “the SLE community might be heartened by the BICLA response.”
She points out that the design of the study, which allowed steroid tapering and thereby lessened placebo responses, lent itself to BICLA response as a study outcome, and Furie and team note that TULIP-2, a similarly designed trial that is also to be presented at the 2019 ACR/ARP Annual Meeting, has assessed BICLA as a primary endpoint.
In all, 41% of 103 patients taking at least 10 mg/day of corticosteroids in addition to anifrolumab reduced their oral corticosteroid dose to a sustained 7.5 mg or less versus 32% of 102 patients taking placebo.
And among patients with a baseline cutaneous lupus erythematosus disease area and severity index (CLASI) activity score of at least 10 points, 42% of 58 receiving anifrolumab reduced this score by at least 50% at 12 weeks, compared with 25% of 54 patients receiving placebo.
Together these secondary endpoint findings “suggest anifrolumab might have clinical benefit for patients with active SLE,” the team concludes.
By Lucy Piper
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