Immunosuppressive therapy found effective in elderly NMOSD patients
Treatment shown to significantly reduce relapses in late-onset disease
Immunosuppressive therapy significantly reduces relapses in elderly people with late-onset neuromyelitis optica spectrum disorder (NMOSD), with more than half of patients becoming relapse-free, a retrospective study in South Korea has found.
Treatment also eased or stabilized disability for most patients, without a marked risk of severe infections, and was generally found to be safe.
In addition, among the immunosuppressive treatments used in these patients, rituximab (sold as Rituxan, among others) showed a more favorable benefit-risk profile than did azathioprine or mycophenolate mofetil (MMF, sold as CellCept), “as seen in previous studies across all age groups,” the researchers wrote.
“Prioritising early and effective IST [immunosuppressive treatment] is crucial for managing NMOSD relapse in elderly patients, with a concomitant emphasis on diligent monitoring of infection risk and treatment-related [adverse events],” the researchers wrote.
The study, “Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study,” was published in the Journal of Neurology, Neurosurgery and Psychiatry.
‘Hesitance’ seen in using immunosuppressive therapy for older patients
NMOSD is marked by abnormal inflammatory attacks against healthy cells that support the nervous system. In most cases, this involves self-reactive antibodies against a protein called AQP4.
The disease typically appears between the ages of 30 and 40, but 1 in every 4 cases occurs among people age 50 or older — when it’s then classified as late-onset NMOSD.
“Age plays a pivotal role in the clinical outcomes and prognosis of NMOSD, with older patients frequently facing poorer prognoses,” the researchers wrote.
While immunosuppressive therapy can prevent NMOSD relapses, “there has been hesitance in administering IST to older patients,” the team noted. That’s likely because these individuals may have additional health conditions, and may experience changes in how the body metabolizes medications that may affect treatment efficacy.
Further, such factors also may increase the risk of infections, multiorgan injury, and death.
Now, a team of researchers from institutions in South Korea evaluated the safety and efficacy of immunosuppressive therapies in 101 elderly people with AQP4-related NMOSD. More than three-quarters (78%) of the patients were women. All had received immunosuppressive treatment, at five Korean hospitals, for at least six months after age 65.
Most (86%) had additional disorders at diagnosis, most often high blood pressure, as seen in 41%, and diabetes, seen in 24%.
In general, patients started immunosuppressive treatment at a mean age of 64.5, about 4.5 years on average after disease onset. They then were followed for a median of 5.8 years.
The most common treatment was azathioprine (60%), followed by MMF (48%) and rituximab (41%) — all commonly used off-label in NMOSD to reduce the risk of relapse. Rituximab, in particular, works by specifically promoting the death of antibody-producing B-cells.
More than half of the patients (64%) started immunosuppressive therapy after experiencing multiple attacks, while 36% started it after the first attack. Nearly half (46%) received at least two sequential immunosuppressive treatments.
Study is first to show treatment effectiveness for late-onset NMOSD
Treatment efficacy was assessed through changes in the annualized relapse rate (ARR) and the Expanded Disability Status Scale (EDSS), a measure of disability.
The ARR was significantly reduced from 0.76 to zero after immunosuppressive therapy, with a 72.4% drop in the number of attacks. A total of 58% of patients remained relapse-free for NMOSD under immunosuppressive treatment.
At the start of treatment, the patients’ median EDSS score was 3.5, reflecting moderate disability, and 44% of these individuals showed severe disability. Among the 96 patients with available EDSS scores throughout the study, 78% experienced either an easing or stabilization of their disability. No differences in outcomes were seen in patients who kept their initial treatment or who switched to a different regimen.
Our study is the first to [show] the effectiveness and safety of [immunosuppressive therapy] in the elderly with NMOSD. … Although long-term [immunosuppressive therapy] can present increased challenges and complexities in elderly patients, its potential benefits may outweigh the risk of severe disability in the absence of [treatment].
In addition, while the ARR was significantly reduced, reaching zero (no relapses), in all three groups, more patients treated initially with rituximab (83%) were relapse-free when compared with azathioprine (66%) or MMF (46%).
A relapse-free survival analysis showed that rituximab was significantly superior to MMF, but only numerically superior to azathioprine at preventing relapses.
During a median treatment period of 3.6 years, 47% of patients experienced infections, with 21% showing severe infections. The most common was pneumonia, affecting 28%, followed by hospitalized COVID-19 infections and kidney infections, which were both seen in 20% of patients.
Severe infections were less frequent among rituximab-treated patients (18% vs. 24% with azathioprine and 15% with MMF), but these differences did not reach statistical significance.
Azathioprine and MMF, but not rituximab, were each associated with adverse events that led to a treatment switch or discontinuation.
“Our study is the first to [show] the effectiveness and safety of IST in the elderly with NMOSD,” the researchers wrote. “Although long-term IST can present increased challenges and complexities in elderly patients, its potential benefits may outweigh the risk of severe disability in the absence of IST.”
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