Conventional NMOSD treatment effective in double-negative cases
Study: Some patients don't test positive for typical disease-driving antibodies
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People with neuromyelitis optica spectrum disorder (NMOSD) who are negative for typical disease-driving antibodies show several differences in clinical features compared with antibody-positive NMOSD patients, but responses to conventional treatments seem largely comparable, according to a new study.
“Our findings support the utility of conventional [immune-suppressing treatments] in this subgroup, while underscoring the need for prospective, mechanistic studies to determine whether [antibody-negative] NMOSD represents a distinct disease entity or a … subset within the broader NMOSD spectrum,” researchers wrote.
The study, “Characterizing double seronegative neuromyelitis optica spectrum disorder: A distinct subgroup or part of the continuum?,” was published in the Journal of Neuroimmunology.
NMOSD often driven by antibodies targeting AQP4
NMOSD is an immune disorder marked by inflammation of the nervous system, particularly the spinal cord and optic nerves, which carry visual information between the brain and eyes. In most patients, the disease is driven by antibodies targeting aquaporin-4 (AQP4), a protein found on the surface of nervous system cells called astrocytes.
There are also people with NMOSD-like disease features who have antibodies targeting a different protein called MOG. This was once considered a subtype of NMOSD, but modern studies have shown that people with anti-MOG antibodies have distinct patterns of disease and treatment response, so they are now diagnosed with a distinct disorder called MOG antibody-associated disease, or MOGAD.
While most people with NMOSD-like disease either have anti-AQP4 antibodies or MOGAD, some show all the signs of NMOSD but don’t test positive for either of these two disease-typical antibodies. Such patients are referred to as double-negative (DN).
Still, it’s currently not clear whether double-negative patients should be considered a subtype of NMOSD or a distinct disease entity like MOGAD.
Double-negative patients showed symptoms indicative of myelitis
To better understand this issue, scientists in Argentina analyzed clinical data from 64 people with AQP4-positive NMOSD, 16 people with MOGAD, and 31 people who were double-negative but met all diagnostic criteria for NMOSD.
At disease onset, double-negative patients were significantly younger (16.2 years) than AQP4-positive or MOGAD patients (19.7 years for both).
Also at onset, patients who were double-negative or positive for AQP4 most commonly had symptoms indicative of myelitis, or spinal cord inflammation, such as issues with movement or sensation. Between 44% and 48% of those patients had myelitis compared with 13% of MODAG patients.
In contrast, MOGAD patients more frequently presented with optic neuritis, or inflammation of the optic nerves (69% versus 47% among AQP4-positive patients and 29% in double-negative patients).
In the first two years after disease onset, double-negative patients had higher relapse rates than AQP4-positive patients. But over several years of total follow-up, double-negative patients had 68% significantly fewer relapses than those with AQP4-positive NMOSD.
This finding “supports the idea of a transiently aggressive disease course early on DN patients,” the researchers said.
Other differences were also noted. For example, on MRI scans, double-negative patients tended to show distinct patterns of nervous system damage, and spinal fluid tests showed that these patients were more frequently positive for inflammation-associated proteins called oligoclonal bands.
Treatment patterns similar across patient groups
Across all three patient groups, treatment patterns were similar. In particular, most patients were treated with rituximab, a medication that depletes B-cells, or immune cells that make antibodies.
Overall treatment response rates were similar across patients who were DN or antibody-positive. The researchers noted, however, that rates of treatment failure with rituximab were actually lower among double-negative patients than in AQP4-positive patients.
These data suggest that conventional immunosuppressive treatments used for antibody-positive NMOSD are also generally effective in double-negative patients, even though they lack the typical disease-driving antibodies.
This is particularly noteworthy, as DN patients are often excluded from NMOSD clinical trials. The researchers said these data emphasize the need for more formal studies of NMOSD treatments in double-negative patients.
The scientists also cautioned that this study is limited by its retrospective nature and the relatively small number of patients. They said further studies are needed to continue investigating whether double-negative patients represent a subtype of NMOSD or their own distinct clinical entity.
