ECTRIMS 2023: NMOSD disability progresses faster than in MOGAD
Long-term analysis of German registry data presented at conference
People with neuromyelitis optica spectrum disorder (NMOSD) experience faster disability progression with fewer attacks than those with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), a related condition, according to a long-term analysis of German registry data.
Notably, in all patients, experiencing inflammation in the optic nerve, which transmits signals between the eye and the brain, as the first disease symptom was significantly associated with a lower risk of disability progression.
The findings were presented by Vivien Häußler, MD, a researcher at the University Medical Center Hamburg-Eppendorf in Germany, during last week’s joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), in Milan and online.
The oral presentation was titled “Long-term disability in NMOSD develops over decades independent from AQP4 serostatus and faster than in MOGAD.”
Taken together, these patient groups “show distinctive latencies to life-time disability accrual, with MOGAD reaching disability milestones later suggesting a more benign disease course,” the researchers wrote in the presentation abstract.
These results add to previous studies showing that MOGAD is associated with a more frequent lesion resolution relative to NMOSD, further supporting the latter as a more aggressive condition.
NMOSD and MOGAD are rare autoimmune diseases characterized by the immune system’s mistaken attack on healthy parts of the nervous system. Most cases of NMOSD are caused by antibodies against aquaporin-4 (AQP4), a protein found in nerve support cells called astrocytes.
On the other hand, MOGAD is caused by antibodies against the myelin oligodendrocyte glycoprotein (MOG).
In both diseases, the autoimmune attacks typically result in inflammation in the spinal cord (transverse myelitis) and/or the optic nerve (optic neuritis). This leads to demyelination, or a loss of the fatty substance that surrounds and protects nerve cells.
Patients typically experience disease relapses, or attacks, interspersed with periods of remission. Patients may fail to completely recover from attacks, leading to long-term damage and the accumulation of disability that may make them become blind or wheelchair-bound.
However, whether NMOSD is associated with a different long-term disability trajectory to MOGAD remains largely unclear, as well as potential risk factors for disability accumulation.
Participants drawn from the NEMOS registry
To learn more, Häußler and colleagues looked at long-term disability data from NMOSD and MOGAD patients who were participating in the German Neuromyelitis Optica Study Group (NEMOS) registry as of September 2021.
Their analysis covered 483 patients: 298 AQP4-related NMOSD patients; 52 NMOSD patients negative for both anti-AQP4 and anti-MOG antibodies; and 133 MOGAD patients.
People with AQP4-related NMOSD were significantly older at disease onset than patients in the other two groups (43.1 vs. 33.6-35.7 years) and had a significantly higher proportion of female patients (90.6% vs. 42.3-57.1%).
While AQP4-related NMOSD patients were more likely to experience transverse myelitis as their first attack, those with MOGAD were more likely to have optic neuritis. The occurrence of the two symptoms was balanced in the antibody-negative NMOSD group.
Disability was monitored over time using the Expanded Disability Status Scale (EDSS), whose scores range from 0-10, and higher scores indicate greater disability. Patients were followed for a mean of 7-10 years, and the time it took to reach specific EDSS milestones was evaluated.
Results showed that NMOSD patients, regardless of antibody status, reached EDSS scores of 3, 4, 6, and 7 significantly faster than MOGAD patients. Generally, these four scores mark shifts from moderate disability, severe disability, the need for a walking aid, and complete loss of walking ability.
MOGAD patients post mighty stats
MOGAD patients took “almost twice as long” to reach these disability milestones, Häußler said.
For example, while those in the AQP4-related NMOSD group took an average of 20.1 years to reach EDSS 6, or disability severe enough to require an aid for walking 100 meters, MOGAD patients reached that milestone after an average of 37.2 years.
The scientist also noted that the time it took for AQP4-NMOSD to reach this disability milestone was “much longer than in historical [patient groups], possibly reflecting more effective treatment strategies we have nowadays.”
In addition, disability accumulation in NMOSD occurred after significantly fewer attacks relative to MOGAD patients. To reach each disability milestone, MOGAD patients experienced more relapses than did NMOSD patients, “possibly suggesting less severe attacks or better recovery,” Häußler said.
Statistical models looking for risk factors of disability accumulation in patients from all groups showed that for each disability milestone, having a disease onset at 50 years or older was associated with a significantly increased risk of reaching those milestones.
In turn, having optic neuritis as the first disease symptom was associated significantly with a lower risk of disease progression.
To assess for the potential impact of the treatment landscape changes seen in the past 10 years, the researchers assessed risk of disability progression before and after 2014. This year corresponds to about a decade after the discovery of anti-AQP4 antibodies, and the time when experts made formal recommendations about treatment courses, Häußler said.
The team found that assessment of disability outcomes after 2014 also was associated significantly with a lower risk of reaching each disability milestone. This indicates that “investigator-initiated collaborative research has led to optimized off-label treatment guidelines that improved disease outcomes for all three patient groups in the last decade,” the researchers wrote in the abstract.
Overall, these findings highlight that “NMOSD patients reach the different disability milestones after a shorter period of time, independent of the [antibody status], [and need] a lower number of attacks to reach those different milestones” relative to MOGAD patients, Häußler said.