Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder

초록

Introduction: The elderly patients with neuromyelitis optica spectrum disorder (NMOSD) consist of both geriatric-onset NMOSD and early-onset NMOSD patients who age naturally into this category. The immunosuppressive treatment (IST) of elderly individuals is challenging due to pre-existing comorbidities, frailty, changes in pharmacokinetics, and immunosenescence. This could frequently result in suboptimal treatment for these individuals, despite reports that late-onset NMOSD is associated with more severe disability. The risk-benefit relationship of IST for elderly patients with NMOSD is not well established. Objectives/Aims: The purpose of this investigation was to assess treatment outcomes in elderly patients with NMOSD. Methods: This retrospective study included 101 patients with NMOSD over the age of 65 who have received IST for at least 3 months from the five centers in Korea. Results: The median age at disease onset was 63 and the female to male ratio was 8:1. The current median age was 69 years (range, 67-73) and 86% of patients had diverse comorbidities, most commonly systemic autoimmune diseases (17%) followed by a history of cancer (13%) and cardiopulmonary disease (10%). The median interval between onset and the initiation of IST was 15 months, and the median Expanded Disability Status Scale score at the initiation of IST was 4.0. Patients were treated with azathioprine (AZA) (n=46), mycophenolate mofetil (MMF) (n=40), and rituximab (n=40) (29 patients received two or more sequential IST). During a median of 44 months of IST (range, 22-68), 58% of patients were relapse-free and the median annualized relapse rate decreased from 1.8 to 0. Patients treated with rituximab had a greater relapse-free rate (63%) than those treated with azathioprine (34%) or MMF (36%). Patients who received AZA (39%) or MMF (39%) discontinued more frequently than those who received rituximab (0%). Most common reason for IST cessation was insufficient efficacy followed by adverse effects. During IST, 20 patients had 24 severe infection events, with two of them dying of pneumonia at ages 79 and 67, respectively, following 3 years of MMF treatment and 4 months of rituximab treatment. Neither new malignancies nor cancer recurrences occurred during IST. Conclusion: In elderly patients with NMOSD, the benefit of IST to prevent relapse appears to outweigh the risk of adverse effects. Rituximab showed a better benefit profile than MMF or AZA in elderly patients with the highest retention rate for clinical response and tolerability. Disclosure of interest: Kim SH, Kim KH, Chung HY, Min JH, Han HJ, Kim SW, Shin HY, Kwon YN, Kim SM, Lee EJ, Lim YM, and Hyun JW: nothing to disclose. Kim HJ received a grant from the National Research Foundation of Korea and research support from Aprilbio and Eisai; received consultancy/speaker fees from Alexion, Aprilbio, Biogen, Celltrion, Daewoong, Eisai, GC Pharma, HanAll BioPharma, MDimune, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva-Handok, UCB, and Viela Bio; is a co-editor for the Multiple Sclerosis Journal and an associated editor for the Journal of Clinical Neurology.