01 Targeting type I interferons

Evidence that the type I interferon pathway plays an important role in the pathogenesis of SLE has been mounting over the last several decades.1-3 Therefore, it was only natural that this pathway be the target of therapeutic interventions in systemic lupus erythematosus (SLE). Although rontalizumab and sifalimumab, the first two monoclonal antibodies directed against interferon alpha to be evaluated in clinical trials, yielded negative and modest clinical trial results, respectively, other pursuits were undertaken that initially proved more successful. Phase II SLE clinical trial data were quite robust with anifrolumab, an antibody to the type I interferon receptor that inhibits all five subtypes of type I interferons.4 These results reaffirmed the clinical significance of type I interferons. This presentation will review various strategies being pursued in order to block the interferon pathway.5 Learning objectives Describe the role of the type I interferon pathway in the pathogenesis of SLE Discuss strategies for inhibiting the type I interferon pathway Analyse results of clinical trials in SLE of interferon inhibitors References Bengtsson AA, Rönnblom L. Role of interferons in SLE. Best Practice & Research Clinical Rheumatology 2017;31(3):415–28. Crow MK, Rönnblom L. Report of the inaugural Interferon Research Summit: interferon in inflammatory diseases. Lupus Sci Med 2018;5(1):e000276. Crow MK, Ronnblom L. Type I interferons in host defence and inflammatory diseases. Lupus Sci Med 2019;6(1):e000336. Furie R, Khamashta M, Merrill JT, et al. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis & Rheumatology 2017;69(2):376–86. Furie R, Werth VP, Merola JF, et al. Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus. Journal of Clinical Investigation 2019;129(3):1359–71.