To compare and rank immunotherapies in MOG-IgG disease for relapse-free survival and reduced ARR using frequentist network meta-analysis. 

MOG-IgG–associated disease is a rare autoimmune disorder with high relapse risk. Optimal immunotherapy for preventing relapses and reducing annualized relapse rates remains unclear.

A systematic search of PubMed, EMBASE, Scopus, and Web of Science (up to September 2025) identified randomized and observational studies evaluating six immunotherapies—IVIG, MMF, Rituximab, Azathioprine, Prednisolone, and Cyclophosphamide in MOGAD. A frequentist graph-theoretical network meta-analysis with a random-effects model using the DerSimonian–Laird estimator (τ²) was applied. Heterogeneity was assessed using I² from Cochran’s Q. Outcomes included relapse-free rate and annualized relapse rate (ARR). Language refinement was assisted by ChatGPT (OpenAI, GPT-5).

A total of 5 studies were included for ARR analysis. Compared with IVIG, Azathioprine showed no significant difference (MD = 0.18, 95% CI: -0.33 to 0.69, p = 0.49), while MMF (MD = 0.19, 95% CI: 0.14–0.24, p < 0.0001), Prednisolone (MD = 0.33, 95% CI: 0.28–0.38, p < 0.0001), and Rituximab (MD = 0.38, 95% CI: 0.33–0.43, p < 0.0001) were associated with significantly higher relapse rates.

In 10 studies analyzing relapse-free survival, all alternatives had lower odds of remaining relapse-free versus IVIG: Azathioprine (OR = 0.23, 95% CI: 0.11-0.46, p < 0.0001), MMF (OR = 0.35, 95% CI: 0.19-0.67, p = 0.0015), Prednisolone (OR = 0.26, 95% CI: 0.13-0.54, p = 0.0003), and Rituximab (OR = 0.27, 95% CI: 0.14-0.51, p < 0.0001). Cyclophosphamide showed a non-significant trend toward worse outcomes (OR = 0.04, 95% CI: 0.001-1.14, p = 0.06)

IVIG is the most effective immunotherapy for both maximizing relapse-free survival and minimizing ARR in MOG-IgG associated disease, with statistically and clinically significant superiority over all alternative