PT  - JOURNAL ARTICLE
AU  - Dalia Rotstein
AU  - Jacqueline M. Solomon
AU  - Maria Pia Sormani
AU  - Xavier Montalban
AU  - Xiang Y. Ye
AU  - Dina Dababneh
AU  - Alexandra Muccilli
AU  - Georges Saab
AU  - Prakesh Shah
TI  - Association of NEDA-4 With No Long-term Disability Progression in Multiple Sclerosis and Comparison With NEDA-3
AID  - 10.1212/NXI.0000000000200032
DP  - 2022 Nov 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e200032
VI  - 9
IP  - 6
4099  - http://nn.neurology.org/content/9/6/e200032.short
4100  - http://nn.neurology.org/content/9/6/e200032.full
SO  - Neurol Neuroimmunol Neuroinflamm2022 Nov 01; 9
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