Type I interferon antagonists in clinical development for lupus

Systemic lupus erythematosus (SLE) is a severe chronic and incurable autoimmune disease. Treatment includes glucocorticoids and immunosuppressants which typically result in partial responses, and hence there is a great need for new therapies. The type I interferon (IFN) pathway is activated in more than 50% of SLE patients, and it is strongly implicated as a pathogenic factor in SLE.

We searched the literature using 'SLE and interferon antagonists' as search terms. This identified a number of therapeutics that have entered clinical development targeting type I IFN in SLE. These include monoclonal antibodies against type I IFN cytokines and a kinoid vaccination strategy to induce anti-IFN antibodies.

Type I IFN antagonists have had some success, but many molecules have not progressed to phase III. These varied results are likely attributed to the multiple concurrent cytokine abnormalities present in SLE, the imprecise nature of the IFN signature as a readout for type I IFN and difficulties with clinical trials such as background medication use and diffuse composite disease activity measures. Despite these challenges, it seems likely that a type I IFN antagonist will come to clinical utility for SLE given the large unmet need and the recent phase III success with anifrolumab.