Comorbidities Are Associated With Unfavorable Outcome in Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Exploratory Study From the CROCTINO Cohort

Abstract

BackgroundComorbidities occur in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and double seronegative NMOSD (DN-NMOSD), potentially contributing to a less favorable disease course.ObjectivesTo characterize comorbidities in AQP4-NMOSD, MOGAD, and DN-NMOSD and assess their association with optic neuritis (ON) outcomes by optical coherence tomography (OCT) in AQP4-NMOSD.MethodsFour hundred and forty-two participants from the CROCTINO cohort were evaluated for comorbidities.ResultsIn AQP4-NMOSD patients (n = 360), 43.5 (n = 161) had comorbidities, equally divided between single and multiple. In MOGAD (n = 49), 40.8 had comorbidities, with 75 (n = 15) single and 25 (n = 5) multiple. In DN-NMOSD (n = 33), 36.4 (n = 12) had comorbidities equally split. AQP4-NMOSD patients had more multiple comorbidities (50, n = 81/161) than MOGAD (25, n = 5/20, p = 0.03) and more autoimmune disorders (AID) (40.4, n = 65) than MOGAD (20, n = 4, p = 0.09) and DN-NMOSD (none, p = 0.004). Cardiovascular comorbidities and related risk factors (CVC/RF) occurred in 34.8 (n = 56) of AQP4-NMOSD, 50 (n = 10) of MOGAD, and 33.3 (n = 4) of DN-NMOSD. Expanded Disability Status Scale was higher in MOGAD (3.0 vs. 2.0, p = 0.006) and DN-NMOSD (5.0 vs. 2.0, p = 0.008) with comorbidities. AQP4-NMOSD patients with CVC/RF had higher ON relapse rates than those with AID (1.06 +/- 3.33 vs. 0.49 +/- 0.98, p < 0.001). OCT revealed reduced inner nuclear layer thickness in AQP4-NMOSD with comorbidities compared to non-comorbidity (B = -1.52, p = 0.047), more pronounced with CVC/RF (B = -2.96, p = 0.009).ConclusionComorbidities are frequent in AQP4-NMOSD and MOGAD and are associated with ON frequency and disability. These findings highlight the need for proactive comorbidity management to improve patient care.