PT  - JOURNAL ARTICLE
AU  - Luca Prosperini
AU  - Serena Ruggieri
AU  - Shalom Haggiag
AU  - Carla Tortorella
AU  - Carlo Pozzilli
AU  - Claudio Gasperini
TI  - Prognostic Accuracy of NEDA-3 in Long-term Outcomes of Multiple Sclerosis
AID  - 10.1212/NXI.0000000000001059
DP  - 2021 Nov 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e1059
VI  - 8
IP  - 6
4099  - http://nn.neurology.org/content/8/6/e1059.short
4100  - http://nn.neurology.org/content/8/6/e1059.full
SO  - Neurol Neuroimmunol Neuroinflamm2021 Nov 01; 8
AB  - Background and Objectives To estimate the proportions of patients with relapsing-remitting multiple sclerosis who despite achieving the no evidence of disease activity-3 (NEDA-3) status in the first 2 treatment years experienced relapse-associated worsening (RAW) or progression independent from relapse activity (PIRA) in the following years.Methods We selected patients with NEDA-3—defined as no relapse, no disability worsening, and no MRI activity—in the first 2 years of either glatiramer acetate or interferon beta as initial treatment. We estimated the long-term probability of subsequent RAW and PIRA (considered as 2 contrasting outcomes) by cumulative incidence functions. Competing risk regressions were used to identify the baseline (i.e., at treatment start) predictors of RAW and PIRA.Results Of 687 patients, 224 (32.6%) had NEDA-3 in the first 2 treatment years. After a median follow-up time of 12 years from treatment start, 58 patients (26%) experienced disability accrual: 31 (14%) had RAW and 27 (12%) had PIRA. RAW was predicted by the presence of >9 T2 lesions (subdistribution hazard ratio [SHR] = 3.92, p = 0.012) and contrast-enhancing lesions (SHR = 2.38, p = 0.047) on baseline MRI scan and either temporary or permanent discontinuation of the initial treatment (SHR = 1.11, p = 0.015). PIRA was predicted by advancing age (SHR = 1.05, p = 0.036 for each year increase) and presence of ≥1 spinal cord lesion on baseline MRI scan (SHR = 4.08, p = 0.016).Discussion The adoption of NEDA-3 criteria led to prognostic misclassification in 1 of 4 patients. Different risk factors were associated with RAW and PIRA, suggesting alternative mechanisms for disability accrual.Classification of Evidence This study provides Class II evidence that in patients with RRMS who attained NEDA-3 status, subsequent RAW was associated with baseline MRI activity and discontinuation of treatment and PIRA was associated with age and the presence of baseline spinal cord lesions.CELs=contrast-enhancing lesions; CIF=cumulative incidence function; DMTs=disease-modifying treatments; EDSS=Expanded Disability Status Scale; GA=glatiramer acetate; IFNB=Interferon beta; NEDA-3=no evidence of disease activity-3; PIRA=progression independent of relapse activity; RAW=relapse-associated worsening; RRMS=relapsing-remitting multiple sclerosis; SHR=subdistribution hazard ratio; MS=multiple sclerosis