PMID- 30285675 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20230918 IS - 1471-2377 (Electronic) IS - 1471-2377 (Linking) VI - 18 IP - 1 DP - 2018 Oct 3 TI - Comparative effectiveness of beta-interferons and glatiramer acetate for relapsing-remitting multiple sclerosis: systematic review and network meta-analysis of trials including recommended dosages. PG - 162 LID - 10.1186/s12883-018-1162-9 [doi] LID - 162 AB - BACKGROUND: We systematically reviewed the comparative effectiveness of injectable beta-interferons (IFN-beta) and glatiramer acetate (GA) on annualised relapse rate (ARR), progression and discontinuation due to adverse events (AEs) in RRMS, using evidence from within the drugs' recommended dosages. METHODS: We updated prior comprehensive reviews, checked references of included studies, contacted experts in the field, and screened websites for relevant publications to locate randomised trials of IFN-beta and GA with recommended dosages in RRMS populations, compared against placebo or other recommended dosages. Abstracts were screened and assessed for inclusion in duplicate and independently. Studies were appraised using the Cochrane risk of bias tool. Rate ratios for ARR, hazard ratios for time to progression, and risk ratios for discontinuation due to AEs were synthesised in separate models using random effects network meta-analysis. RESULTS: We identified 24 studies reported in 42 publications. Most studies were at high risk of bias in at least one domain. All drugs had a beneficial effect on ARR as compared to placebo, but not compared to each other, and findings were robust to sensitivity analysis. We considered time to progression confirmed at 3 months and confirmed at 6 months in separate models; while both models suggested that the included drugs were effective, findings were not consistent between models. Discontinuation due to AEs did not appear to be different between drugs. CONCLUSIONS: Meta-analyses confirmed that IFN-beta and GA reduce ARR and generally delay progression as defined in these trials, though there was no clear 'winner' across outcomes. Findings are additionally tempered by the high risk of bias across studies, and the use of an impairment/mobility scale to measure disease progression. Future research should consider more relevant measures of disability and, given that most trials have been short-term, consider a longitudinal approach to comparative effectiveness. REVIEW REGISTRATION: PROSPERO CRD42016043278 . FAU - Melendez-Torres, G J AU - Melendez-Torres GJ AUID- ORCID: 0000-0002-9823-4790 AD - Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. g.melendez-torres@warwick.ac.uk. FAU - Armoiry, Xavier AU - Armoiry X AD - Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. FAU - Court, Rachel AU - Court R AD - Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. FAU - Patterson, Jacoby AU - Patterson J AD - Independent research consultant, Windsor, UK. FAU - Kan, Alan AU - Kan A AD - Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. FAU - Auguste, Peter AU - Auguste P AD - Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. FAU - Madan, Jason AU - Madan J AD - Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. FAU - Counsell, Carl AU - Counsell C AD - Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK. FAU - Ciccarelli, Olga AU - Ciccarelli O AD - Queen Square Multiple Sclerosis Centre, University College London Institute of Neurology, London, UK. AD - National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, UK. FAU - Clarke, Aileen AU - Clarke A AD - Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. LA - eng GR - ID809/Health Technology Assessment Programme/ PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20181003 PL - England TA - BMC Neurol JT - BMC neurology JID - 100968555 RN - 0 (Immunosuppressive Agents) RN - 5M691HL4BO (Glatiramer Acetate) RN - 77238-31-4 (Interferon-beta) SB - IM MH - Disease Progression MH - Glatiramer Acetate/*therapeutic use MH - Humans MH - Immunosuppressive Agents/*therapeutic use MH - Interferon-beta/*therapeutic use MH - Multiple Sclerosis, Relapsing-Remitting/*drug therapy MH - Network Meta-Analysis PMC - PMC6169084 OTO - NOTNLM OT - Beta-interferon OT - Clinically isolated syndrome OT - Economic evaluation OT - Glatiramer acetate OT - Multiple sclerosis OT - Systematic review COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study did not require ethics approval. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: Prof. Olga Ciccarelli received consultancy fees from Teva, Roche, Novartis, Biogen Idec, and Genzyme. She also received funds for research from the UK MS Society, National MS Society, EPSRC, Rosetree Trust; her research is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). She is an Associate Editor of Neurology for which she receives an honorarium. Dr. Carl Counsell received funding through Biogen Idec, who previously provided some funding for a departmental MS nurse. Dr. Carl Counsell has also authored a paper that was critical of the UK Risk Sharing Scheme for disease modifying therapies in MS (Sudlow, CLM, Counsell, CE. Problems with UK government's risk sharing scheme for assessing drugs for multiple sclerosis. BMJ 2003; 326:388-392). The remaining authors have no competing interests to declare. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/10/05 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/10/03 CRDT- 2018/10/05 06:00 PHST- 2018/01/17 00:00 [received] PHST- 2018/09/21 00:00 [accepted] PHST- 2018/10/05 06:00 [entrez] PHST- 2018/10/05 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/10/03 00:00 [pmc-release] AID - 10.1186/s12883-018-1162-9 [pii] AID - 1162 [pii] AID - 10.1186/s12883-018-1162-9 [doi] PST - epublish SO - BMC Neurol. 2018 Oct 3;18(1):162. doi: 10.1186/s12883-018-1162-9.