To assess potential associations among relapse profile and treatment change in patients with neuromyelitis optica spectrum disorder (NMOSD) participating in the CIRCLES study from 2013 to 2020.

The IRB-approved longitudinal, observational CIRCLES study was conducted at 15 North American medical centers. Patients having at least 60 days of follow-up and an on-study maintenance treatment were evaluated. Hazard ratios (HRs) for treatment change were derived from Cox proportional hazards models of relapse features:  self-reported pre-study annual relapse rate (ARR); on-study relapse(s); and on-study relapse phenotypes. Relapses were incorporated as time-varying covariates to estimate relationship to treatment change.

Of 542 patients studied, 158 (29.2%) experienced at least one relapse. Cumulatively, 131 patients (24.2%) changed treatment regimen on-study. In bivariate analyses, factors associated with significantly increased likelihood of treatment change were self-reported pre-study ARR > 0.75 (vs. < 0.25; HR = 2.98; p<0.001) and on-study relapse (HR = 2.53, p<0.001). Classified by phenotype, relapses including optic neuritis (ON) were significantly associated with treatment change with or without brain involvement (HR = 3.53, p<0.001) or with transverse myelitis (HR = 3.68, p=0.001).  Results from multivariate analyses were concordant.

In CIRCLES patients, features correlating with change in treatment regimen included a higher pre-study ARR, on-study relapse event, and ON relapse phenotypes in particular. These findings suggest patient relapse profiles may drive or predict treatment change in NMOSD. Such relationships may facilitate therapeutic decision-making to minimize relapse impact and to enhance quality of life in patients with NMOSD as the field enters the new era of approved therapies.