INTRODUCTION: The type 1 interferon pathway is known to play a role in the immunopathology of systemic lupus erythematosus (SLE). As a result, biologic agents targeting this pathway have been developed and are currently being investigated in clinical trials. AREAS COVERED: We review the biologic agents which have been developed to antagonize type I interferons in SLE. We focus on anifrolumab, a type I interferon receptor antagonist, and consider the complexities of defining efficacy in SLE clinical trials. EXPERT OPINION: Anifrolumab shows promise as an addition to the SLE therapeutic armamentarium. Despite discordant results between its two phase III studies, there is a convincing suggestion of benefit in both trials to encourage the view that this approach might be effective. Data acquired thus far look particularly useful for cutaneous disease. We await data on its effect on renal, pulmonary, cardiac, and central nervous system involvement, on patient reported outcomes, and its safety and efficacy with long-term use