Clinical Benefit of Adjunctive Rituximab in Anti–Interferon-Gamma Autoantibody-Associated Immunodeficiency: A Retrospective Self-Controlled Cohort Study

Abstract Background Antimicrobial therapy is the cornerstone of treatment for anti–interferon-gamma (IFN-γ) autoantibody-associated immunodeficiency (AOID), but persistent or relapsing infections remain challenging. We evaluated outcomes associated with adjunctive rituximab in patients with AOID. Methods We conducted a retrospective self-controlled cohort study of adult patients with AOID treated at a tertiary care hospital in Northern Thailand between January 2019 and December 2024. Each patient contributed data from two treatment periods: antimicrobial therapy alone and with adjunctive rituximab. Clinical and laboratory outcomes were compared over three-month observation windows. Results Among 14 patients with AOID, the mean age was 61.00 ± 8.84 years, and 6 patients (42.86%) were male. NTM infection was present in all patients. Rapidly growing mycobacteria (RGM) infections were the predominant NTM infections in both treatment periods, occurring in 13 patients (92.86%). Compared with the antimicrobial-only period, adjunctive rituximab was associated with a significantly higher likelihood of successful antimicrobial de-escalation (adjusted odds ratio, 5.38; 95% confidence interval [CI], 1.16–25.00; P = .032). Rituximab exposure was also associated with a greater reduction in absolute lymphocyte count (adjusted β, −379 cells/µL; 95% CI, −725 to −33; P = .032) and a modest increase in alkaline phosphatase (adjusted β, 32.8 U/L; 95% CI, 8.7–56.9; P = .008). No rituximab-associated infusion reactions, hypersensitivity reactions, severe infections related to immunosuppression, or deaths were observed. Conclusion Adjunctive rituximab was associated with a higher likelihood of successful antimicrobial de-escalation without major short-term safety concerns. Further prospective evaluation is warranted.