Optimal management of neuromyelitis optica spectrum disorder with aquaporin-4 antibody by oral prednisolone maintenance therapy

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing neuroinflammatory disease associated with aquaporin-4 antibody. Since disabilities in patients with NMOSD accumulate with attacks, relapse prevention is crucially important for improving long-term outcomes. Corticosteroids are inexpensive and promising drugs for relapse prevention in NMOSD, but few studies have analysed the efficacy of corticosteroids in NMOSD, especially regarding the appropriate dosing and tapering regimens. Methods: A single-center, retrospective analysis of corticosteroid therapy in aquaporin-4 antibody-positive NMOSD patients fulfilling the 2015 international consensus diagnostic criteria was conducted. Results: Medical records of a total of 89 Japanese patients with aquaporin-4 antibody-positive NMOSD seen at Department of Neurology, Tohoku University Hospital (2000 similar to 2016) were reviewed. At the last follow-up, 66% of the patients were treated with prednisolone (PSL) monotherapy, and the percentage of those receiving PSL monotherapy or a combination of PSL and other immunosuppressants increased from 17.5% in 2000 to 94.1% in 2016. On the other hand, annualised relapse rate (ARR) decreased from 0.78 (13 attacks in 200 person-months) in 2000 to 0.07 (5 attacks in 819 person-months) in 2016. Under PSL treatment, the mean ARR significantly decreased, and disabilities stabilized (PSL treatment vs no-medication; ARR: 0.21 vs 0.98, P < 0.01, Expanded Disability Status Scale score change: +0.02 vs +0.89, P < 0.01, observation periods: 60.1 vs 68.2 months, P=0.26). Using Kaplan-Meier curves, the 10-year relapse-free rate was 46.5% with PSL monotherapy and 7.1% with no medication (hazard ratio: 0.069, 95% confidence interval [CI] 0.024-0.199, P < 0.01). Rapid tapering of PSL (10 mg or less in one year and/or 5 mg or less in two years after clinical attacks) was associated with frequent relapses compared to gradual tapering (more than 10 mg in one year and more than 5 mg in two years after clinical attacks) (rapid vs gradual, 36.7% vs 17.7%, odds ratio 2.69, 95% CI 1.12-6.44, P = 0.02). However, even with PSL of 5 mg/day or less, the relapse rate was low after two years of acute treatment (before vs after, 53.8% vs 13.6%, odds ratio 0.12, 95% CI 0.03-0.50, P < 0.01). Nine patients needed additional immunosuppressants due to insufficient relapse prevention by PSL monotherapy. PSL monotherapy was generally well tolerated, but seven patients had severe adverse events, mainly bone fractures (5 with bone fracture, 1 with femoral capital necrosis and 1 with cerebral infarction). Conclusion: Our study suggests that PSL monotherapy is effective to prevent relapses in about half of patients with aquaporin-4 antibody-positive NMOSD if the doses are gradually reduced. Although it is important to have a treatment strategy tailored to each patient, this study provides evidence that PSL monotherapy can be an option for relapse prevention in some patients with NMOSD.