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Abstract
Background and Objectives Exit strategies such as de-escalations have not been evaluated for rituximab in patients with neuromyelitis optica spectrum disorder (NMOSD). We hypothesized that they are associated with disease reactivations and aimed to estimate this risk.
Methods We describe a case series of real-world de-escalations from the French NMOSD registry (NOMADMUS). All patients met the 2015 International Panel for NMO Diagnosis (IPND) diagnostic criteria for NMOSD. A computerized screening of the registry extracted patients with rituximab de-escalations and at least 12 months of subsequent follow-up. We searched for 7 de-escalation regimens: scheduled discontinuations or switches to an oral treatment after single infusion cycles, scheduled discontinuations or switches to an oral treatment after periodic infusions, de-escalations before pregnancies, de-escalations after tolerance issues, and increased infusion intervals. Rituximab discontinuations motivated by inefficacy or for unknown purposes were excluded. The primary outcome was the absolute risk of NMOSD reactivation (one or more relapses) at 12 months. AQP4+ and AQP4− serotypes were analyzed separately.
Results We identified 137 rituximab de-escalations between 2006 and 2019 that corresponded to a predefined group: 13 discontinuations after a single infusion cycle, 6 switches to an oral treatment after a single infusion cycle, 9 discontinuations after periodic infusions, 5 switches to an oral treatment after periodic infusions, 4 de-escalations before pregnancies, 9 de-escalations after tolerance issues, and 91 increased infusion intervals. No group remained relapse-free over the whole de-escalation follow-up (mean: 3.2 years; range: 0.79–9.5), except pregnancies in AQP+ patients. In all groups combined and within 12 months, reactivations occurred after 11/119 de-escalations in patients with AQP4+ NMOSD (9.2%, 95% CI [4.7–15.9]), from 0.69 to 10.0 months, and in 5/18 de-escalations in patients with AQP4− NMOSD (27.8%, 95% CI [9.7–53.5]), from 1.1 to 9.9 months.
Discussion There is a risk of NMOSD reactivation whatever the rituximab de-escalation regimen.
Trial Registration Information Registered on ClinicalTrials.gov: NCT02850705.
Classification of Evidence This study provides Class IV evidence that de-escalation of rituximab increases the probability of disease reactivation.
Glossary
- AQP4-IgG=
- aquaporin 4-IgG;
- EDSS=
- Expanded Disability Status Scale;
- MOGAD=
- myelin oligodendrocyte glycoprotein antibody disease;
- MOG-IgG=
- myelin oligodendrocyte glycoprotein antibodies;
- MS=
- multiple sclerosis;
- NMOSD=
- neuromyelitis optica spectrum disorder;
- RCTs=
- randomized clinical trials
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
NOMADMUS Study Group coinvestigators are listed in the appendix at the end of the article.
Submitted and externally peer reviewed. The handling editor was Deputy Editor Olga Ciccarelli, MD, PhD, FRCP.
Editorial, page 153
Class of Evidence: NPub.org/coe
- Received August 21, 2022.
- Accepted in final form April 7, 2023.
- © 2023 American Academy of Neurology
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