Painstaking research over more than two decades has demonstrated the essential role that activation of the type 1 interferon system plays in a considerable subset of patients with systemic lupus erythematosus (SLE). Based on these observations down-regulation of this system became a logical therapeutic goal. Following limited success with anti-interferon monoclonal antibodies, the monoclonal antibody anifrolumab, which binds the type 1 interferon receptor and thereby interferes with the ligands’ binding to that receptor, was developed successfully in a clinical trial program. The Phase 2 data and subsequent Phase 3 data, taken in aggregate, were accepted by regulators as sufficiently strong evidence for efficacy, and acceptable safety, for the compound to be approved for use in patients with active SLE. Several salient points from these trials include:

• Efficacy was more consistently demonstrated using the BICLA than with the SRI–4

• Efficacy was seen in both skin and joints, the most prevalent manifestations in these trials

• Among adverse events, herpes zoster seemed most clearly elevated for anifrolumab compared with placebo

More learnings from these trials, beyond initial efficacy and safety, have also been reported and will provide additional information in the future.

Learning Objectives

• Describe the scientific rationale and mechanisms of action of anifrolumab

• Explain the main efficacy data from the anifrolumab clinical trials programme

• Explain of the main safety data from the anifrolumab clinical trials programme

• Discuss what additional learnings have emerged and will likely emerge from these clinical trials