Initiation of Maintenance Therapy After First Attack Improves Long-Term Relapse Risk, Disease Trajectory in MOGAD

Romain Marigner, MD, PhD

A 2024 study published in Neurology using patients with myelin oligonucleotide glycoprotein antibody-associated disease (MOGAD) showed that initiating maintenance treatment after their first attack was associated with a significantly lower relapse risk over patients’ life. In this longitudinal analysis, the highest risk of relapse in MOGAD occurred early, and most patients had favorable motor and visual long-term outcome.

Otherwise known as the MOGADOR2 study, the research included 128 adults with a first event of MOGAD who were in the French nationwide incident cohort from February 2014 and March 2017. Led by senior author Romain Marigner, MD, PhD, a professor in the Neurological Hospital of Lyon, France, the most common phenotype at onset was isolated optic neuritis (ON; 63.3%; unilateral: 37.5%; bilateral: 25.8%) followed by isolated myelitis (19.5%), and ON and myelitis (8.6%). Of note, only 11 patients (8.6%) had neither ON nor myelitis at onset.

The cohort’s median age at onset was 37.5 years, with a median Expanded Disability Status Scale (EDSS) score of 3 (mean, 3.3; range, 0-9) at their disease onset. Over a median follow-up of 77.8 months, 61.7% (n = 79) of patients had no relapse whereas 38.3% (n = 49) experienced at least 1 relapse during follow-up. Of the 80 patients on maintenance therapy, most (72.5%) received one therapy, while 21.25%, 5%, and 1.25% received two, three, or four therapies, respectively. Rituximab was the most common first-line treatment (38.75%), followed by azathioprine (30.0%) and mycophenolate mofetil (21.25%), with others including corticosteroids, mitoxantrone, and multiple sclerosis (MS) disease-modifying drugs.

At the last follow-up, 63.75% (51 of 80) who started maintenance therapy were still treated. Using a multivariate analysis, data showed that older age at onset (OR, 1.07; 95% CI, 1.03-1.12; P = .001), higher EDSS at onset (OR, 1.39; 1.06-1.89; P = .002), the number of attacks (OR, 1.78; 95% CI, 1.13-2.82; P = .001) and initiation of maintenance treatment after second attack (OR, 5.41; 95% C, 1.39-23.05; P = .002) were significantly associated with EDSS at last follow-up. The same could not be said for sex, follow-up duration, phenotype at onset, presence of autoantibodies, CSF pleocytosis, oligoclonal band (OCB) in CSF, MOG antibody-negative seroreversion, maintenance treatment started after onset attack, and a relapsing course.

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"Considering the mostly favorable recovery from disease attacks after acute treatment, the frequent occurrence of a monophasic course and the infectious risks associated with immunosuppressive agents, the decision to initiate maintenance treatment in MOGAD is a complex one," the study authors wrote. "Currently, maintenance immunotherapy is typically initiated at the time of a second attack or if there is no or poor recovery from the first attack. In our study, near 40% of patients started preventive treatment from the onset attack and we found that the relapse risk was significantly lower in these patients. This benefit was related to a significant reduction in relapse risk within the first year."

In multivariate analysis, the initiation of maintenance treatment after first event and before a possible second attack (OR, 0.26; 95% CI, 0.11-0.62; P = .002) was associated with lower risk of relapsing course. In patients who began maintenance therapy after the first attack, the risk of relapse was 11% at 2 years, 15% at 4 years, and 20% at both 6 and 8 years. For those who did not start maintenance therapy after the first attack, the relapse risk was higher: 41% at 2 years, 46% at 4 years, 51% at 6 years, and 56% at 8 years.

The study had some limitations, including the fact that it comprised only patients from French referral centers for neuroinflammatory disorders, which may introduce selection bias, though the geographical distribution of these centers likely minimizes this risk. The focus on cases from 2014–2017 excludes newer phenotypes, such as cortical encephalitis, and patients treated with recently validated therapies like long-term steroids or IVIG. Small subgroup sizes limit statistical analysis, and varying protocols across centers affected consistency in treatment approaches, follow-ups, and documentation of therapy changes.

REFERENCE
1. Deschamps R, Guillaume J, Ciron J, et al. Early Maintenance Treatment Initiation and Relapse Risk Mitigation After a First Event of MOGAD in Adults: The MOGADOR2 Study. Neurology. 2024;103(3). doi:10.1212/WNL.0000000000209624