Assessment of disability and disease burden in neuromyelitis optica spectrum disorders in the CIRCLES Cohort

Abstract

Neuromyelitis optica spectrum disorders (NMOSD) comprise autoimmune diseases imposing substantial disability. We compared an NMOSD-targeted disability assessment of mobility, vision, and self-care domains (individually and composite) with the multiple sclerosis-targeted Expanded Disability Status Scale (EDSS) to assess NMOSD disease burden. An overall cohort (n = 505) and a subset of these patients with an enriched dataset (n = 198) were analyzed from the CIRCLES longitudinal, observational database of patients with AQP4-IgG-seropositive or -seronegative NMOSD in North America. Multinomial modeling was used to identify temporal correlates of disability improvement, stability, and worsening. Prior on-study relapse correlated with worsening mobility (OR, 3.08; 95% CI: 1.61-5.90), vision (OR, 3.99; 95% CI: 2.03-7.86), self-care disability (OR, 1.90; 95% CI: 1.07-3.38), and mean composite index disability (OR, 4.20; 95% CI: 1.71-10.34). Higher vision disability was associated with Black race, shorter time on-study, and AQP4-IgG-seropositive status in patients ≥ 18 years (p < 0.05). Disease onset phenotype and sex correlated with pain interference (p < 0.05). These correlates of NMOSD disability were undetected by EDSS. The CIRCLES real-world experience supports the need for NMOSD-specific disability assessment to improve recognition of disease burden, facilitate proactive clinical management, offer insights into resilience, and inform clinical trial design.

Fig. 1

Assessment of clinical variables associated with worsened and improved mobility (panels A and B) or vision (panels C and D) compared with stability (neither improved nor worsened). Odds ratio (95% CI); red = significant association (p<0.05); blue = non-significant association (p>0.05). AQP4-IgG, aquaporin-4 immunoglobulin G; AAR, annualized relapse rate; BPI, Brief Pain Inventory; MoCA, Montreal Cognitive Assessment; OR, odds ratio. Panels A & B represent results from patients in Cohort 1 for whom mobility data were available. Panels C & D represent results from patients in Cohort 1 for whom vision data were available. ^aHigher value of the score reflects worse disability. ^bReference, male; ^cReference, White. ^d Reference, age 35 to 48 years. ^e Reference, anti–AQP4-IgG seronegative. ^f Reference, 1 to 5 years. ^g Reference, ARR<0.25. ^h Reference, no prior on-study relapse. ⁱ Reference, no prior treatment change. ^j Binary variable indicating that MoCA, severity, and intensity scores are not available. ^k Reference, before 2017.

Fig. 2

Assessment of clinical variables associated with self-care disability (panels A and B) or composite index score (panels C and D) as compared to stability (neither improved nor worsened). Odds ratio (95% CI); red = significant association (p<0.05); blue = non-significant association (p>0.05)AQP4-IgG, aquaporin-4 immunoglobulin G; AAR, annualized relapse rate; BPI, Brief Pain Inventory; MoCA, Montreal Cognitive Assessment; OR, odds ratio. Panels A & B represent results from patients in Cohort 1 for whom self-care data were available. Panels C & D represent results from patients in Cohort 1 for whom composite data were available. ^aHigher value of the score reflect worse disability. ^bReference, male; ^cReference, White. ^d Reference, age 35 to 48 years. ^e Reference, anti-AQP4–IgG seronegative. ^f Reference, 1 to 5 years. ^g Reference, ARR<0.25. ^h Reference, no prior on-study relapse. ⁱ Reference, no prior treatment change. ^j Binary variable indicating that MoCA, severity and intensity scores are not available. ^k Reference, before 2017.

Fig. 3

The 7-point disability scales in the vision (A),^a mobility (B),^b and self-care (C)^c domains, derived from patients with NMOSD.  NMOSD, neuromyelitis optica spectrum disorders.^a Visual acuity based on best corrected eye (corrective lenses, pinhole, or refraction). ^b Mobility scores reflecting wheelchair or equivalent assume impaired ability to transfer, ambulate, or both. ^c Self-care disability score derives from a cumulative 3-point score for each activity of daily life assessed as follows: attend school/work or perform routine housework; bathing/showering; bowel/bladder management; personal grooming; dressing; food preparation; eating. Each of these activities is independently scored as 0 = independent; 1 = partially dependent; 2 = completely dependent. Scores for each of these activities are summed for the overall self-care disability score; higher scores indicate greater disability.