Anakinra as a diagnostic challenge and treatment option for systemic autoinflammatory disorders of undefined etiology

Background: Some adult patients presenting with unexplained pyrexia, serositis, skin rashes, arthralgia, myalgia, and other symptoms commonly found in autoinflammatory disorders may not fit a specific diagnosis, either because their clinical phenotype is non-diagnostic or genetic tests are negative. We used the term undifferentiated systemic autoinflammatory disorder (uSAID) to describe such cases. Given that well-defined autoinflammatory diseases show responses to interleukin-1 blockade, we evaluated whether anakinra was useful for both diagnosing and treating uSAID patients. Methods: We performed a retrospective analysis of consecutive patients, presenting with uSAID between 2012-2015, who were treated with the recombinant interleukin-1 (IL-1) receptor antagonist, anakinra. uSAID was diagnosed after excluding malignancy, infection, and pathogenic mutations in known hereditary fever syndromes (HFS) genes, and where clinical criteria for adult onset Still's disease (AOSD) were not met. Results A total of 11 patients presented with uSAID (5 males and 6 females), with a mean time to diagnosis of 3.5 years (1.0-8.0 years). Patients were unresponsive or only partially controlled on DMARD/steroid treatment. Anakinra controlled symptoms within 4-6 weeks of starting treatment in 9/11 cases. Two patients discontinued therapy; one due to incomplete response, and another due to severe injection site reactions. Conclusion: This retrospective case series demonstrates that the spectrum of poorly defined autoinflammatory disorders that show responsiveness to anakinra is considerable. Anakinra seems a viable treatment option for these patients who are unresponsive to standard steroid/DMARD treatments. Moreover, given the mechanisms of action, response to anakinra implicates underlying IL-1 dysregulation in the disease pathogenesis of responding uSAIDs patients.