Immunosuppressive treatment may lower DN-NMOSD relapse risk
Review study supports early treatment for antibody-negative patients
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Immunosuppressive treatments can reduce the risk of disease relapses in people with neuromyelitis optica spectrum disorder (NMOSD) who test negative for known disease-driving antibodies, a review study showed.
Because relapses in these patients often lead to permanent disability, the findings suggest that immunosuppressive treatment should be given early to minimize the risk of long-term disability. However, researchers were unable to determine which specific medication is most effective for this subgroup of NMOSD patients.
The review study, “Double-Negative Neuromyelitis Optica Spectrum Disorder: A Systematic Review and Meta-Analysis,” was published in Neurology Neuroimmunology & Neuroinflammation.
NMOSD is caused when the immune system wrongly attacks healthy cells in the brain and spinal cord. Most NMOSD cases test positive for self-reactive antibodies that target aquaporin-4 (AQP4), a protein highly present at the surface of neuron-supporting cells.
Immunosuppressants and antibodies
Some people have NMOSD-like symptoms that are driven by antibodies targeting a different protein called myelin oligodendrocyte glycoprotein (MOG). While this used to be considered an NMOSD subtype, it is now typically classified as a separate entity called MOG antibody disease (MOGAD).
People with NMOSD features and symptoms but testing negative for self-reactive antibodies against either AQP4 or MOG are said to have double-negative NMOSD (DN-NMOSD).
NMOSD is typically characterized by flares, in which NMOSD symptoms suddenly worsen in response to new immune activity, interspersed by periods of remission, or few to no symptoms. NMOSD treatments mainly aim to reduce the risk of relapse. However, most of these therapies are specifically indicated for AQP4-related NMOSD.
Current guidelines call for people with DN-NMOSD to be treated with immunosuppressive meds similar to those used for AQP4-related NMOSD or MOGAD, but no comprehensive studies on treatment efficacy have been done in this patient population.
A team of scientists in Italy combed through the available scientific literature, aiming to understand what’s currently known about DN-NMOSD and how best to treat it.
A total of 41 studies, covering 671 people with DN-NMOSD from 23 countries, were included in the final analysis. Patients’ median age at the onset of symptoms was 38.6, and 61% were women. The spinal cord and eye nerves were the two most commonly affected regions. All these are features comparable to those seen in AQP4-related NMOSD.
Nearly three-quarters of the patients (73.6%) experienced disease relapses. And when a relapse occurred, symptoms often didn’t go away even after the relapse was resolved, leading to lasting disability. This is similar to AQP4-related NMOSD, but it contrasts with MOGAD, in which symptoms often ease considerably once a flare is under control.
Because relapses are common and often lead to long-term problems, the researchers argued that early treatment to prevent relapses should be prioritized in DN-NMOSD.
“Our data suggest that, in the absence of precise biomarkers, early maintenance immunotherapy even after the first attack should be considered to prevent further disability accumulation,” the team wrote.
To better understand relapse rates and treatment response in DN-NMOSD, the researchers conducted a meta-analysis, pooling data from 16 of the studies.
Pooled data from six studies in DN-NMOSD patients showed that relapse rates were significantly reduced with treatment. However, there was high variability between studies.
“Current guidelines suggest that, because attacks in DN-NMOSD can be severe and with incomplete recovery, patients should be treated with immunosuppressive drugs such as rituximab, but this is largely based on expert opinion,” the researchers wrote. “Our data strengthen this indication, even though the [variability] between studies remains high.”
No significant differences were detected among people with DN-NMOSD, AQP4-related NMOSD, and MOGAD in terms of relapse rates before and after treatment, suggesting comparable responses to treatment across groups.
The researchers attempted to compare different types of immunosuppressive drugs in DN-NMOSD patients, but because there was so much variability among the studies, they couldn’t get definitive results.
“We did not find a significantly relevant effect of a specific treatment compared with another, but the data [variability] prevented us from performing a proper comparison,” the scientists wrote. “Therefore, at present, we cannot provide further indication on which treatment should be preferred in DN-NMOSD.”
“Future studies should investigate and compare the efficacy of each immunosuppressive drug to help define the optimal treatment strategy,” they concluded.
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