Azathioprine for remission maintenance in anti-interferon-γ autoantibody-associated immunodeficiency syndrome- a retrospective single-center cohort study

Abstract

Background: Anti-interferon-γ autoantibody (Anti-IFN-γ Aab) disease is associated with frequent recurrent infections. Adjunctive immunosuppressive treatment, including rituximab, can achieve disease remission. However, disease relapses and recurrent infections occur after immunosuppressive drugs are discontinued. Azathioprine (AZA) is used for maintenance therapy in many autoimmune diseases with few adverse effects. This study aimed to assess the effectiveness of AZA in maintaining clinical remission in patients with Anti-IFN-γ Aab disease. Methods: This retrospective observational study was conducted at Ramathibodi Hospital, Thailand, from 2019 to 2023. The study involved two patient groups with Anti-IFN-; Aab disease who received maintenance therapy with AZA and without AZA, respectively. The patients’ demographics, clinical disease courses, and other relevant information were collected. Results: Of the 29 sampled patients, 15 received AZA maintenance therapy, and 14 did not. There were no notable differences between the groups regarding demographics (age and sex), clinical presentation, identified pathogens, and infection episodes before initiating immunosuppressive treatment or the induction regimen. The Kaplan–Meier 50% cumulative survival analysis of disease relapse time was 3.99 years in the AZA group compared to 0.88 years in the group without AZA. The covariate-adjusted survival curve estimations of the durations of antimicrobial treatments, Anti-IFN-γ Aab inhibition titers before AZA initiation, and induction regimens showed a hazard ratio of 0.096 (p=0.006, 95%CI: 0.018–0.507) in the AZA group. Conclusion: AZA was generally safe and associated with prolonged remission in Anti-IFN-; Aab disease and reducing relapse rates, despite the occurrence of some breakthrough infections. Clinical trial number: Not applicable