RT Journal Article SR Electronic T1 Association of NEDA-4 With No Long-term Disability Progression in Multiple Sclerosis and Comparison With NEDA-3 JF Neurology - Neuroimmunology Neuroinflammation JO Neurol Neuroimmunol Neuroinflamm FD Lippincott Williams & Wilkins SP e200032 DO 10.1212/NXI.0000000000200032 VO 9 IS 6 A1 Dalia Rotstein A1 Jacqueline M. Solomon A1 Maria Pia Sormani A1 Xavier Montalban A1 Xiang Y. Ye A1 Dina Dababneh A1 Alexandra Muccilli A1 Georges Saab A1 Prakesh Shah YR 2022 UL http://nn.neurology.org/content/9/6/e200032.abstract AB Background and Objectives No evidence of disease activity (NEDA)-4 has been suggested as a treatment target for disease-modifying therapy (DMT) in relapsing-remitting multiple sclerosis (RRMS). However, the ability of NEDA-4 to discriminate long-term outcomes in MS and how its performance compares with NEDA-3 remain uncertain. We conducted a systematic review and meta-analysis to evaluate (1) the association between NEDA-4 and no long-term disability progression in MS and (2) the comparative performance of NEDA-3 and NEDA-4 in predicting no long-term disability progression.Methods English-language abstracts and manuscripts were systematically searched in MEDLINE, Embase, and the Cochrane databases from January 2006 to November 2021 and reviewed independently by 2 investigators. We selected studies that assessed NEDA-4 at 1 or 2 years after DMT start and had at least 4 years of follow-up for determination of no confirmed disability progression. We conducted a meta-analysis using random-effects model to determine the pooled odds ratio (OR) for no disability progression with NEDA-4 vs EDA-4. For the comparative analysis, we selected studies that evaluated both NEDA-3 and NEDA-4 with at least 4 years of follow-up and examined the difference in the association of NEDA-3 and NEDA-4 with no disability progression.Results Five studies of 1,000 patients (3 interferon beta and 2 fingolimod) met inclusion criteria for both objectives. The median duration of follow-up was 6 years (interquartile range: 4–6 years). The prevalence of NEDA-4 ranged from 4.2% to 13.9% on interferon beta therapy and 24.9% to 25.1% on fingolimod therapy. The pooled OR for no long-term confirmed disability progression with NEDA-4 vs EDA-4 was 2.14 (95% confidence interval: 1.36–3.37; I2 = 0). We did not observe any significant difference between NEDA-4 and NEDA-3 in the comparative analyses.Discussion In patients with RRMS, NEDA-4 at 1–2 years was associated with 2 times higher odds of no long-term disability progression, at 6 years compared with EDA-4, but offered no advantage over NEDA-3.BVL=brain volume loss; CI=confidence interval; DMT=disease-modifying therapie; EDA=evidence of disease activity; MS=multiple sclerosis; NEDA=no evidence of disease activity; NfL=neurofilament light chain; OR=odds ratio; PIRA=progression independent of relapse activity; RCT=randomized controlled trial; RRMS=relapsing-remitting MS; SPMS=secondary progressive MS