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. 2021 Aug 9;8(6):e1059.
doi: 10.1212/NXI.0000000000001059. Print 2021 Nov.

Prognostic Accuracy of NEDA-3 in Long-term Outcomes of Multiple Sclerosis

Luca Prosperini  1 , Serena Ruggieri  2 , Shalom Haggiag  2 , Carla Tortorella  2 , Carlo Pozzilli  2 , Claudio Gasperini  2
Affiliations

Prognostic Accuracy of NEDA-3 in Long-term Outcomes of Multiple Sclerosis

Luca Prosperini et al. Neurol Neuroimmunol Neuroinflamm. .

Abstract

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.

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Figures

Figure 1
Figure 1. Study Flowchart of Patients' Disposition
Figure 2
Figure 2. (A) Cumulative Incidence Functions of Progression Relapse-Associated Worsening (RAW) and Progression Independent From Relapse Activity (PIRA) in Patients With No Evidence of Disease Activity-3 (NEDA-3) After 2 Years From Treatment Start; (B) Disability Changes, Expressed as Step of Expanded Disability Status Scale (EDSS), by Long-term Outcomes (n = 224)
Figure 3
Figure 3. Proportion of Patients Experiencing Relapse-Associated Worsening (RAW) and Progression Independent From Relapse Activity (PIRA) by Disease Activity After 2 Years From Treatment Start (Median Follow-up Time of 12 Years)
EDA-3 = evidence of disease activity-3 (n = 463); NEDA-3 = no evidence of disease activity-3 (n = 224).
See this image and copyright information in PMC

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