Research in context
Evidence before this study
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with manifestations in multiple organs. Evidence supports dysregulation of the type I interferon pathway in SLE pathogenesis. Anifrolumab is a human monoclonal antibody that binds to the type I interferon-α receptor subunit 1 and inhibits the effects of all type I interferon subtypes on gene expression and downstream inflammatory and immunological sequelae. We searched ClinicalTrials.gov and PubMed for all studies registered or published in English, respectively, up to March 29, 2021, with the search terms (“anifrolumab” [All Fields]) AND (“systemic lupus erythematosus” [All Fields]). The search identified one phase 1 trial, two phase 2 trials, one phase 2b trial, one phase 2b long-term extension, one phase 2b exposure–response analysis, and two phase 3 trials of anifrolumab in patients with moderate-to-severe SLE. The search also identified one pooled analysis of safety in the phase 3 TULIP-1 and TULIP-2 trials. Although TULIP-1 did not achieve its primary endpoint, the two phase 3 TULIP trials of anifrolumab 300 mg given intravenously to patients with moderate-to-severe SLE showed that anifrolumab treatment was associated with improved overall disease activity, reduced glucocorticoid use and flares, and improved skin disease.
Added value of this study
This post-hoc analysis of pooled data from the pivotal TULIP-1 and TULIP-2 trials, which were undertaken in patients with moderate-to-severe active SLE, the majority of whom were female and mostly aged 30–50 years, examined the effect of anifrolumab on organ-specific disease manifestations. Anifrolumab, when added to standard SLE therapy, was effective in reducing disease activity across organ systems most commonly affected at trial entry, including the musculoskeletal, mucocutaneous, and immunological domains.
Implications of all the available evidence
Anifrolumab has recently been approved in the USA for the treatment of patients aged 18 years or older with moderate-to-severe SLE, who are receiving standard therapy. Given the clinical heterogeneity of SLE, a particularly important attribute of a new therapy is its ability to reduce disease activity regardless of the pattern of organ system involvement. This post-hoc analysis shows the capacity of anifrolumab to treat diverse SLE manifestations.