The prospective pilot study of cyclophosphamide as an adjunct treatment in patients with adult-onset immunodeficiency associated with anti-interferon-γ autoantibodies

Background: Adult-onset immunodeficiency associated with interferon-gamma autoantibody (IGA) is an emerging disease. The majority of patients require both antimicrobial and immunosuppressive treatments. However, anti-CD20 therapy is not fully accessible in a resource-limited setting to date. Background: The objectives of this work were to study the efficacy of cyclophosphamide treatment and the role of laboratory biomarkers for disease progression monitoring. Methods: A prospective pilot cohort study was conducted among patients with anti-interferon-gamma autoantibodies (IGA) who had recurrent infections and required long-term antimicrobial therapy between 2015 and 2018. The patients were categorized into 2 groups: receipt of intravenous cyclophosphamide (IVCY) and receipt of anti-CD20 therapy (RTX). Clinical and laboratory data were determined. Results: A total of 17 IGA patients were enrolled. Prolonged fever was the most common manifestation, and the most common infection identified was nontuberculous mycobacterial infections. Both were found in 88.24% of all patients.After completion of IVCY, 9/11 patients achieved complete remission and tended to reach remission faster compared with individuals in the RTX group. The median duration from treatment initiation to remission (interquartile range) was 84 (42-154) days in the IVCY group and 99 (51-202) days in the RTX group. In remission patients, the biomarkers of interest had normalized after treatment, except interferon gamma autoantibody titers. There were no differences in adverse events among the 2 groups. Conclusion: IVCY may be considered as alternative therapy in this population, especially in resource-limited countries. A comparable clinical outcome to RTX may support its use on a larger scale. However, further study is encouraged.