Clinical and epidemiological correlates of treatment change in patients with NMOSD: insights from the CIRCLES cohort

Abstract

Objective: Neuromyelitis optica spectrum disorders (NMOSD) represent rare autoimmune diseases of the central nervous system largely targeting optic nerve(s) and spinal cord. The present analysis used real-world data to identify clinical and epidemiological correlates of treatment change in patients with NMOSD.

Methods: CIRCLES is a longitudinal, observational study of NMOSD conducted at 15 centers across North America. Patients with ≥ 60 days of follow-up and receiving on-study maintenance treatment were evaluated. The mean annual relapse rate (ARR) was estimated using negative binomial models; the likelihood of treatment change was estimated using Cox proportional hazards models. Relapses were included as time-varying covariates to estimate the relationship to treatment change.

Results: Of 542 patients included, 171 (31.5%) experienced ≥ 1 relapse on the study and 133 patients (24.5%) had ≥ 1 change in the treatment regimen. Two categories of variables significantly correlated with the likelihood of treatment change: (1) relapse: any on-study relapse (hazard ratio [HR] = 2.91; p < 0.001), relapse phenotypes (HR range = 2.15-5.49; p < 0.001), and pre-study ARR > 0.75 (HR 2.28; p < 0.001); 2) disease phenotype: brain syndrome only vs transverse myelitis involvement at onset (HR 2.44; p = 0.008), disease duration < 1 vs > 5 years (HR 1.66; p = 0.028), or autoimmune comorbidity (HR 1.55; p = 0.015). A subset of these factors significantly correlated with shorter time to first rituximab discontinuation.

Conclusions: In CIRCLES, relapse patterns and disease phenotype significantly correlated with changes in the maintenance treatment regimen. Such findings may facilitate the identification of patients with NMOSD who are likely to benefit from treatment change to reduce relapse risk or disease burden and enhance the quality of life.

Keywords: AQP4; Demographics; Neuromyelitis optica spectrum disorder; Relapse; Treatment.

Fig. 1

Hazard ratios for time to first treatment change. ^aReference female. ^bReference White. ^cReference < 30 years. ^dReference seropositivity. ^eReference > 5 years. ^fReference no autoimmune disease comorbidity. ^gReference no AZA; ^hReference no MMF; ⁱReference no oral CS; ^jReference TM, TM + BR. ^kReference no prior on-study relapse. ^lReference pre-study ARR < 0.25. anti–AQP4-IgG, aquaporin-4 autoantibody; ARR, annualized relapse rate; AZA, azathioprine; BR, brain involvement; CS, corticosteroids; HR, hazard ratio; MMF, mycophenolate mofetil; ON, optic neuritis; TM, transverse myelitis

Fig. 2

On-study ARR by race/ethnicity and sex. ARR, annualized relapse rate

Fig. 3

HRs for time to first rituximab discontinuation among patients on rituximab (at least two doses). ^aReference female. ^bReference White. ^cReference seropositivity. ^dReference 30–49 years. ^eReference > 5 years. ^fReference ARR < 0.25. ^gReference ON, ON + BR. ^hReference no comorbidity. ⁱReference no rheumatoid arthritis. ^jReference no lupus. ^kReference no myasthenia gravis. ^lReference no Sjögren syndrome. ^mReference no on-study relapse. anti–AQP4-IgG, aquaporin 4 autoantibody; ARR, annualized relapse rate; BR, brain involvement; HR, hazard ratio; ON, optic neuritis; TM, transverse myelitis