This insightful article contributes new data including clinical characteristics, disability and treatment patterns over time for adults with aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) in Canada. ^{Reference Momen, Freedman and Fadda1} The CAnadian Neuromyelitis OPTIca Spectrum Disorder and other atypical demyelinating diseases Cohort Study (CANOPTICS) is a prospective longitudinal study that included data from seven centers across Canada. Notably, there was a lower median Expanded Disability Status Scale (EDSS) score compared to other cohorts, a paucity of orbital MRI imaging for participants, and increasing use of high-efficacy therapies (rituximab and monoclonal antibodies) over time.

Orbital imaging was done in 13% of participants, and only 34.1% of participants with documented vision loss had an orbital MRI at the index event. This reflects an opportunity for improvement in care for Canadian NMOSD patients. Individuals with AQP4+ NMOSD have distinct MRI lesion patterns compared to individuals with myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) and multiple sclerosis. ^{Reference Leitner, Chew and Blanch2} All individuals with a first-time clinical event and new diagnosis of AQP4+ NMOSD would benefit from MRI orbital imaging, particularly all individuals with optic neuritis.

Individuals were more likely to be treated with azathioprine and mycophenolate mofetil as first-line therapies compared to higher efficacy therapies. The authors hypothesize this could be due to therapeutic inertia. ^{Reference Cobo-Calvo, Gómez-Ballesteros and Orviz3} Many participants likely had their first clinical attack before high-efficacy treatments were widely available and prior to the “early high-efficacy” treatment paradigm gaining support. If patients are stable on oral agents, expert opinion is that treatment escalation is not required. ^{Reference Paul, Marignier and Palace4} Another contributing factor includes variability across Canada in access to high-efficacy therapies driven by provincial drug access programs.

The authors included robust discussions limitations of the study. A large proportion of the cohort had ELISA (42.3%), rather than cell-based assay confirmation of AQP4 (57.7%), a test that has lower sensitivity and specificity. ^{Reference Prain, Woodhall and Vincent5} While all participants included in the study were reviewed by the CANOPTICS research team, this introduces the possibility of misclassification bias. Perhaps the cohort has better clinical outcomes and EDSS scores because some did not have NMOSD. However, another possibility is that around 66% of the cohort had disease onset in the past 10 years, in the age of higher efficacy treatments.

This article provides valuable insights about persons living with AQP4+ NMOSD within Canada. In the future, as the number of institutions and clinics in CANOPTICS expands, more longitudinal data will be captured to inform care for NMOSD patients within Canada and globally.