A new study has found that a high proportion of MS patients with no evidence of disease activity (NEDA) in the first two years of treatment will experience relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) (Prosperini et al. Neurol Neuroimmunol Neuroinflamm 2021;8:e1059).

The retrospective cohort study included 224 MS patients (baseline EDSS <3.0) who achieved NEDA in the first two years of treatment with an injectable disease-modifying therapy. NEDA was defined as no relapses, 6-month confirmed increase in EDSS score, and no new MRI activity. RAW was defined as sustained disability worsening within 3 months after a relapse; PIRA was defined as sustained disability in a relapse-free patient.

During the median 12-year follow-up, 35% experienced a relapse and 39% had new MRI activity despite their initial NEDA status. Overall, 26% of patients experienced an accrual of disability: 14% was attributed to RAW and 12% to PIRA. The median time from treatment start to RAW or PIRA was 10 and 9 years, respectively. There was no difference in the median EDSS change from baseline between the RAW and PIRA groups at 12 years.

Risk factors for RAW included the presence of contrast-enhancing lesions (hazard ratio 2.38), presence of >9 T2 lesions (HR 3.92), and treatment interruption or discontinuation (HR 1.11). Risk factors for PIRA included increasing age (HR 1.05 per year), and the presence of spinal cord lesions at baseline (HR 4.08).

The authors concluded that 1 in 4 patients who achieve early NEDA will be misclassified as being at low risk of disability worsening. They noted that NEDA is a composite measure of inflammation and focal demyelination, and it fails to account for more subtle features that are more prognostic of disability progression, such as diffuse inflammatory damage and neurodegeneration.