No evidence of disease activity (NEDA) is viewed as an important goal in relapsing multiple sclerosis (MS) and has been advocated as a benchmark for treatment decisions. However, NEDA status is maintained only by a minority of MS patients over prolonged periods, regardless of disease-modifying treatment. The predictive value and utility of NEDA in guiding individual therapy remains unclear.
To investigate the association of NEDA-3 status and criteria subitems in a one-year reference period with subsequent disease activity.
We included 113 patients (age 35 ± 10 years, 67 (59.3%) female) with relapsing remitting MS who had annual clinical and MRI follow-up visits. There were no restrictions on disease-modifying therapy. The first year of follow-up was considered the reference period. Patients had a median of 2.8 years follow-up time (interquartile range 1.1 - 4.0 years) after the reference period. NEDA-3 status was established based on relapse assessment, 1-point increase in the expanded disability status scale (EDSS, unrelated to relapse activity) and the appearance of new T2-weighted or contrast-enhancing lesions.
Patients who failed NEDA-3 criteria during the reference period had an increased rate of subsequent NEDA-3 failure (Hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.12-3.02, p=0.0165). Attacks and new lesions during the reference period were associated with a new relapse (HR 2.872, CI 1.31-6.30, p=0.00843) or a new lesion (HR 2.57, CI 1.49-4.43, p=0.000691) during subsequent follow-up, respectively. An EDSS increase in the reference period was not predictive of a future failure of NEDA-3.
Relapses and new lesions increase the risk of future disease activity in relapsing-remitting MS, irrespective of disease-modifying therapy. Relapse-independent disability progression appears to be less useful in predicting future disease activity.