| المساهمون: |
Institut Català de la Salut, [Rotstein D] Department of Medicine, University of Toronto, Ontario, Canada, St. Michael’s Hospital, Toronto, Ontario, Canada. [Solomon JM] Department of Medicine, McMaster University, Hamilton, Ontario, Canada. [Sormani MP] Department of Health Sciences, Section of Biostatistics, University of Genova, Italy, IRCCS Ospedale Policlinico San Martino, Genova, Italy. [Montalban X] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Ye XY] Department of Pediatrics, Mount Sinai Hospital, Toronto, Canada. [Dababneh D] Columbia University Irving Medical Center, Department of Neurology, New York City, New York Presbyterian Hospital (NYP), New York City, Vall d'Hebron Barcelona Hospital Campus |
| الوصف: |
Background and ObjectivesNo 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.MethodsEnglish-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.ResultsFive 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.DiscussionIn 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. |
