Disability in NMOSD patients may worsen even without relapses
Study also finds immunosuppressive therapy lowers progression risk
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Disability worsening in people with neuromyelitis optica spectrum disorder (NMOSD) is largely driven by relapses, or episodes when new symptoms emerge or existing symptoms worsen, but it may also occur in the absence of such episodes.
That’s according to a study analyzing international data from 261 NMOSD patients, which showed that nearly one in five worsening events occurred without a recorded relapse or another identifiable medical explanation.
“Our findings support relapses as the principal driver of disability in neuromyelitis optica spectrum disease while also providing evidence of relapse-independent disability worsening beyond identifiable [other medical conditions],” researchers wrote.
Longer exposure to immunosuppressive treatments, which are used in NMOSD to reduce the risk of relapses, was associated with a lower risk of disability worsening, reinforcing the importance of preventing relapses to limit lasting disability.
The study, “How patients with neuromyelitis optica spectrum disease accumulate disability,” was published in the Multiple Sclerosis Journal.
NMOSD typically follows a relapsing-remitting course
NMOSD occurs when the immune system mistakenly targets healthy cells in the nervous system, causing inflammation and damage, particularly in the spinal cord and optic nerves, which carry visual signals from the eyes to the brain. This results in symptoms like vision loss, muscle weakness, and difficulty walking.
The disease typically follows a relapsing-remitting course, in which relapses are followed by periods of remission when symptoms ease. NMOSD has traditionally been considered a disease in which worsening disability develops almost entirely because of irreversible nerve damage caused by relapses.
Growing evidence, however, suggests that some patients may experience nerve damage and disability worsening even without obvious relapses, which “warrants an in-depth investigation into the intricate interplay between relapses and disability over time,” the researchers wrote.
To investigate, an international team of researchers analyzed data collected through May 2023 from 261 people with NMOSD enrolled in the MSBase registry, an international registry tracking people with inflammatory neurological diseases.
Most disability worsening was associated with relapses
Most participants were women (83.9%), and their median age at symptom onset was 32 years. All had self-reactive antibodies against the AQP4 protein, the most common type of disease-driving antibodies in NMOSD.
At their first visit, participants had been living with NMOSD for a median of 1.5 years. Their median score on the validated Expanded Disability Status Scale (EDSS) was three, indicating moderate disability without walking problems. Participants were followed for a median of nearly 2.5 years.
During follow-up, participants received various immunosuppressive treatments, most commonly azathioprine and rituximab (sold as Rituxan and others) — both used off-label for NMOSD — with each received by 116 patients (44.4%).
The researchers first tracked relapses, defined as new or worsening symptoms lasting at least 24 hours, occurring at least 30 days after a previous relapse, and not explained by fever or another illness. During follow-up, 279 relapses were recorded in 120 participants.
To understand how disability accumulated over time, the team examined increases in EDSS scores, indicating disability worsening, that persisted through the end of follow-up. Worsening was classified as relapse-associated if it occurred within 12 months of a relapse, or relapse-independent if it occurred more than 12 months afterward.
Most disability worsening was associated with relapses, particularly earlier in the disease course. Relapse-independent worsening appeared to account for a greater share over time, although the researchers cautioned that this pattern should be interpreted carefully because the group of patients contributing data changed over time.
Almost 19% of worsening occurred in the absence of relapses
The team also examined confirmed disability-worsening events, defined as increases in EDSS scores that met a minimum threshold based on a person’s previous disability level, were confirmed at least six months later, and persisted through the end of follow-up.
Overall, 32 such events were identified in 31 participants (11.9%), most of which (81.3%) were associated with relapses. Relapses were also significantly associated with a twofold higher chance of confirmed disability worsening.
However, six events (18.7%), affecting five patients (1.9%), occurred in the absence of a relapse. A review of medical records found no other identifiable medical explanation for these events, which mainly involved worsening problems with balance and coordination, vision, muscle strength, and thinking abilities.
Additional analyses demonstrated that spending a greater proportion of follow-up time on immunosuppressive treatments was associated with a 3% lower chance of confirmed disability worsening, “presumably mainly through reducing the risk of relapses”, the researchers wrote.
“While relapses are the predominant driver of disability worsening in NMOSD, they are not the sole contributor,” the team wrote, adding that “almost 19% of worsening occurred in the absence of relapses, reassuringly in only 2% of patients.”
They called for further research to understand the biological processes that lead to disability worsening in NMOSD.
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