Older age at NMOSD onset may raise disease relapse risk
Study sees higher risk for patients older than 32 testing negative for 2 antibodies
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For a rare group of neuromyelitis optica spectrum disorder (NMOSD) patients who test negative for two self-reactive antibodies, being older than 32 at disease onset may increase the risk of relapses, a study found.
In contrast, spinal cord involvement, with or without optic nerve inflammation, at disease onset was significantly associated with a lower relapse rate in these so-called double-seronegative NMOSD (DSN-NMOSD) patients.
“Our study revealed that specific demographic and clinical characteristics were associated with relapse rates in DSN-NMOSD,” the researchers wrote. “However, further research with a larger, more diverse, longer follow-up is necessary to validate these conclusions.”
The study, “Relapse risk factors in double seronegative neuromyelitis optica spectrum disorder: Insights from a multicenter study,” was published in Multiple Sclerosis and Related Disorders.
NMOSD is an autoimmune disease that typically causes inflammation and damage to the spinal cord and optic nerves, which carry visual signals between the brain and eyes. In most cases, NMOSD is characterized by relapses, which are periods when inflammatory attacks cause new or worsening symptoms.
No approved treatment for rare group of patients
Most NMOSD patients have self-reactive antibodies targeting the AQP4 protein on astrocytes, a type of nerve-supporting cell. About 20% of those without anti-AQP4 antibodies have antibodies targeting the MOG protein and are now considered to have a separate, yet similar, condition called MOG antibody-associated disease (MOGAD).
“The identification of these two biomarkers has revealed a population of patients who are persistently [negative] for both [AQP4- and MOG-targeting antibodies], known as double seronegative NMOSD (DSN-NMOSD),” the researchers wrote. “DSN-NMOSD remains a rare condition with … [an] ongoing debate about whether [it] represents a collection of new as-yet-undiagnosed conditions that mimic NMOSD or if these are individuals with immunity to AQP4 or MOG but whose antibodies are undetectable.”
This rare group of patients appears to have distinct demographic and clinical features relative to AQP4-related NMOSD, and have no approved treatments.
The international team of researchers aimed to identify risk factors associated with relapse rates in DSN-NMOSD patients, as well as disease characteristics and treatment outcomes.
They retrospectively analyzed data from 46 DSN-NMOSD patients at three medical centers in the U.S., Brazil, and Turkey, of whom 35 had relapsing disease, accumulating a total of 104 relapse episodes over a 15-year follow-up period. The other 11 patients had experienced a single inflammatory attack (monophasic group).
In the relapsing group, almost half (49%) had optic nerve inflammation (optic neuritis) at disease onset, while 46% had spinal cord inflammation (transverse myelitis). All those in the monophasic group and 5% of those in the relapsing group had both manifestations at disease onset.
There were no significant differences between the two groups of patients in the distribution of spinal cord lesions detected on MRI scans, immune blood cell profile, or signs of inflammation in cerebrospinal fluid, the fluid that bathes the brain and spinal cord.
Statistical analyses adjusted for potential influencing factors, including sex, laterality of optic neuritis, and use of disease-modifying therapy, showed that a disease onset after age 32 was significantly linked to an 82% higher rate of relapse.
In contrast, transverse myelitis at onset was significantly associated with a 59% lower relapse rate, and simultaneous transverse myelitis and optic neuritis at onset was linked to a 96% lower relapse rate.
Patients had a median of two relapses, with a median time to first relapse of 15 months and an annualized relapse rate (ARR) of 0.32. ARR refers to the mean number of attacks per year, considering the overall follow-up time.
No variables were identified as significantly associated with the first relapse.
“As there are currently no approved maintenance therapies for DSN-NMOSD, the management of this condition heavily depends on the discretion of physicians and the availability of medications, [and] future observational studies on the effectiveness of immunotherapies [and] effect of age at onset on disability progression would be highly beneficial in understanding this disease,” the researchers wrote.
