Beneficial effects of intravenous immunoglobulin as an add-on therapy to azathioprine for NMO-IgG-seropositive neuromyelitis optica spectrum disorders

Background: The efficacy of intravenous immunoglobulin (IVIG) in neuromyelitis optica spectrum disorders (NMOSD) has rarely been investigated, despite it being a conceivable therapeutic strategy based on its mode of action. We aimed to evaluate the efficacy of IVIG as an add-on therapy to azathioprine in the prevention of NMOSD relapse.

Methods: We retrospectively reviewed the medical records of NMO-IgG-positive NMOSD patients treated with IVIG infusions (0.4 g/kg/day) every one to three months as a part of combination therapy with azathioprine for more than six months. Treatment efficacy and safety were assessed based on the changes in the pre-IVIG and post-IVIG treatment annualized relapse rates (ARR), and on the proportion of relapse-free and progression-free patients and adverse events.

Results: This study was performed on 20 patients (19 women; median age 52 years). After add-on therapy with IVIG, 19 patients (95%) showed a significant reduction in the median ARR from 1.1 [interquartile range, 0.6‒1.4] to 0.3 [interquartile range, 0‒0.6] (p < 0.001). Seven patients (35%) were relapse-free during 43.5 months (median) of treatment. The median Expanded Disability Status Scale (EDSS) score remained stable at 4.0. In addition, 80% of the patients showed no disability progression, and 25% of the patients experienced an improvement in EDSS. The median NMO-IgG titer decreased from 1:480 (n = 19) to 1:120 (n = 13) after treatment (p = 0.006) and was found to be negative in three patients. Six patients (30%) stopped IVIG due to relapses after 27.5 months (median; interquartile range, 15.3‒43.3) of IVIG initiation. There were no severe side effects that led to discontinuation of IVIG.

Conclusion: IVIG as add-on therapy may be associated with beneficial effects in preventing relapse and disability progression in NMO-IgG-positive NMOSD patients who have breakthrough disease activity despite immunosuppressive treatment with azathioprine. Further randomized controlled trials are necessary to validate the efficacy of IVIG in NMOSD.