NMOSD Relapse Risk Prevalent After Discontinuation of Immunosuppressive Therapy


More than 80% of those with NMOSD experienced disease relapse 6 months after discontinuation of immunosuppressive therapy.

Findings from a retrospective review indicate that immunosuppressive therapy (IST) discontinuation leads to an increased risk of relapse in seropositive patients with neuromyelitis optica spectrum disorder (NMOSD) despite lengthy relapse-free periods. Patients with a history of severe attack before IST may be cautious because of the risk of irreversible disability, even from a single attack.

Lead author Su-Hyun Kim, MD, Department of Neurology, National Cancer Center, Goyang-si, South Korea, and colleagues evaluated the outcomes of IST discontinuation in 17 aquaporin-4 (AQP4) antibody-positive patients with NMOSD who had been relapse-free for at least 3 years. Patient demographics, treatment history, relapse history, and disabilities, as measured by Expanded Disability Status Scale (EDSS) were all collected. Severe relapse was defined as an EDSS score of at least 6, or as new worsening of visual acuity of less than or equal to 0.1 points at the nadir of the attack.

IST was discontinued after a median relapse-free period of 62 months (interquartile range [IQR], 48-73). Patient’s decision (n = 8; 47%) and provider advice (n = 8; 47%) were the most common reasons for discontinuation, while preparing for pregnancy (n = 1; 6%) was also among the reasons. There were no significant safety issues among the 17 patients during the IST period.

Following discontinuation, 14 patients (82%) experienced a relapse at a median interval of 6 months (IQR, 4-34). The median interval was 4 months (IQR, 3-18) for patients (n = 12) who discontinued azathioprine (Imuran; Prometheus Laboratories) or mycophenolate mofetil (CellCept; Genentech). Among the 2 patients who discontinued ritixumab (Rituxan; Genentech/Biogen), the median interval of relapse was 54 and 85 months, respectively.

READ MORE: First Patients Enrolled in SPHERES Registry for Neuromyelitis Optica Spectrum Disorder

"In conclusion, although evaluation of the balance between risk and benefit of maintaining long-term IST should be individualized, this study advocates continuing relapse prevention therapy in seropositive patients with NMOSD, until future studies enable us to determine when and in which patients IST can be safely discontinued and/or until validated biomarkers to predict relapse well in advance are available," the study authors wrote.

Eight patients (47%) experienced severe attacks before IST initiation, whereas 3 (21%) of 14 patients experienced severe attacks after discontinuation of OST. Notably, all 3 patients had a history of severe attack before IST. These 3 patients received steroids followed by plasma exchange for acute treatment, but 2 exhibited poor recovery and EDSS worsening at 6 months after the attacks.

More than 60% of the patients were continuously seropositive. Moreover, among 5 patients with negative seroconversion at the time of discontinuation, all except 1 exhibited positive seroreversion after IST discontinuation, and the time interval from seroreversion to relapse varied between patients. The remaining 11 patients were continuously seropositive for AQP4 antibodies regardless of the treatment, and 2 patients were in a remission state without IST for 65 and 30 months, respectively.

All 14 patients who relapsed after IST discontinuation restarted IST immediately. All but 2 had a stable disease course for a median duration of 29 months (IQR, 13-62) since IST was restarted. These 2 patients attempted IST discontinuation again after 14 and 49 months of treatment with azathioprine and mycophenolate mofetil and relapsed after 3 and 10 months of discontinuation, respectively.

Kim S, Jang H, Park NY, et al. Discontinuation of immunosuppressive therapy in patients with neuromyelitis optica spectrum disorder with aquaporin-4 antibodies. Neurology. 2021;8(2). doi:10.1212/NXI.0000000000000947
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