Late-onset NMOSD responds better to newer, highly effective therapies
People treated after age 50 had fewer relapses than with standard drugs
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Newer, more potent therapies offer greater benefit than standard immunosuppressants in reducing relapse rates for people who develop neuromyelitis optica spectrum disorder (NMOSD) after the age of 50, according to a large, single-center study in China.
While people with late-onset NMOSD experienced more severe symptoms at onset and during relapses than those diagnosed before age 50, nearly all who began treatment with more potent therapies remained relapse-free at the last follow-up.
“Patients with [late-onset NMOSD] may choose highly effective treatments as a first-line therapy,” the researchers wrote.
The study, “Severe attacks and worse prognosis in patients with late-onset neuromyelitis optica spectrum disorder highlight the need for early highly effective treatment,” was published in the Journal of Neurology.
What happens in NMOSD and how it affects the body
In NMOSD, the immune system produces self-reactive antibodies that mistakenly attack healthy cells in the nervous system. In most people with the disease, these antibodies target aquaporin-4 (AQP4), a water channel protein found on the surface of cells that support nerve function.
NMOSD most often causes myelitis, or inflammation of the spinal cord, and/or optic neuritis, inflammation of the nerve that connects the eye to the brain. Myelitis can lead to weakness in the arms and legs, while optic neuritis can cause eye pain and vision loss. These episodes of inflammation, called attacks or relapses, usually recur over time and are separated by periods of remission.
Previous studies have shown that late-onset NMOSD is linked to worse symptoms and more brain lesions, and that these patients are more likely to experience worse recovery from relapses and faster disability progression than those who develop NMOSD before 50.
“Prompt initiation of relapse-preventing immunotherapy is the standard of care for all patients diagnosed with [AQP4-related] NMOSD, irrespective of age at onset, to mitigate the risk of relapse and accumulation of disability,” the researchers wrote.
Classical immunosuppressive therapies (ISTs), such as azathioprine (sold as Imuran and others) and mycophenolate mofetil (sold as CellCept), are often used off-label together with oral corticosteroids. This combination is considered a moderately effective way to prevent relapses.
Rituximab (sold as Rituxan, among others) is an antibody-based immunotherapy that has shown better relapse prevention than traditional ISTs in NMOSD, although it is not formally approved for the disease, and some patients still experience relapses while taking it.
More recently, four potent antibody-based therapies have been approved for people with NMOSD and anti-AQP4 antibodies: Soliris (eculizumab), Ultomiris (ravulizumab-cwvz), Uplizna (inebilizumab-cdon), and Enspryng (satralizumab-mwge).
Nevertheless, it’s unclear whether these newer therapies offer superior safety and efficacy compared with standard ISTs in people with late-onset NMOSD.
To find out, a team of researchers in China examined the medical records of 695 adults (88% women) with AQP4 antibody-positive NMOSD. Of these, 208 people (29.9%) were age 50 or older when their symptoms began.
Study highlights differences between late- and early-onset NMOSD
The team first compared the clinical characteristics of people with late- and early-onset NMOSD and confirmed that those in the late-onset group generally had more severe symptoms at the time of their first attack.
During the first attack, acute myelitis was more common in people with late-onset disease than in those with early-onset disease (47.6% vs. 31.2%). By contrast, optic neuritis (28.8% vs. 37.6%) and attacks involving the brain or the brainstem-spinal cord region (8.2% vs. 10.3%) were less common in late-onset patients.
People with late-onset disease also experienced a more severe first attack, as shown by significantly higher scores on the Expanded Disability Status Scale (EDSS). They also had more relapses per year on average (0.50 vs. 0.47), and a higher proportion experienced severe relapses (53.8% vs. 39.6%).
By the last follow-up visit, the late-onset group continued to have significantly higher EDSS scores (3.0 vs. 2.5) and was more likely to have moderate-to-severe motor disability (20.7% vs. 8.6%).
Most late-onset patients (81.7%) initially received moderately effective treatment, while 18.3% were given highly effective therapies such as rituximab, Enspryng, or Uplizna.
Prompt initiation of relapse-preventing immunotherapy is the standard of care for all patients diagnosed with [AQP4-related] NMOSD, irrespective of age at onset, to mitigate the risk of relapse and accumulation of disability.
After a median of 3.08 years of follow-up while on treatment, nearly all of those who received highly effective therapies (94.7%) remained relapse-free, compared with 67.1% of those on moderately effective treatment. Patients who switched from moderately effective medications to highly effective therapies also experienced a drop in their average relapse rate.
Both treatment approaches reduced the average number of relapses per year, but the rate was significantly lower in the highly effective therapy group. Among the people who did relapse while taking highly effective therapies, those relapses tended to occur soon after treatment began. By comparison, patients on moderately effective therapies relapsed after a median of 16.2 months. Even so, the likelihood of remaining relapse-free remained high over time relative to moderately effective therapies.
Further statistical analyses showed that highly effective therapies were associated with about a 76% lower risk of relapse compared with moderately effective treatment. Relapse risk increased by about 8.5% for each one-unit increase in body mass index.
In terms of safety, the rate of serious infections was similar between the highly effective and moderately effective treatment groups (7.58% vs. 5.63%), and there were no infection-related deaths reported.
“The main strength of our findings is that patients receiving highly effective treatments are at a lower risk of relapse than those receiving classical ISTs; however, this is not associated with a higher risk of [serious infections] compared with ISTs,” the team wrote. “Future large … studies [following patients over time] are warranted to investigate the long-term efficacy and safety of these highly effective treatments.”
