title: Comparative effectiveness of biologics for the management of rheumatoid arthritis: systematic review and network meta-analysis.
abstract: Our aim was to establish the comparative effectiveness of rheumatoid arthritis (RA) biologics, using a systematic review and network meta-analysis. The systematic review used randomized controlled trials (RCTs) in adults with RA who failed treatment with conventional disease-modifying agents for rheumatoid disease (cDMARDs). We compared the effectiveness of abatacept, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, and rituximab to tocilizumab, a recent biologic with a different mechanism of action (anti-IL-6 receptor). A network meta-analysis (NMA) included the indirect and direct evidence previously selected. In total, 207 articles were included describing 68 RCTs. The NMA showed that tocilizumab monotherapy was superior to standard care (ACR20, OR 13.27, 95 % CrI [3.958, 43.98]; ACR50, 17.45 [10.18, 31.24]; ACR70, 37.77 [7.226, 216.3]; EULAR, 10.42 [1.963, 54.8]); and methotrexate (MTX; ACR50, OR 5.44 [4.142, 7.238]; ACR70, 7.364 [1.4, 30.83]; EULAR, 4.226 [1.184, 15.58]) at 26 weeks. Similarly, the combination of tocilizumab + MTX was significantly better than standard care/placebo and MTX alone for ACR20, ACR50, ACR70, and EULAR at 26 weeks (OR 18.63 [5.32, 66.81]; 24.27 [14.5, 41.91]; 46.13 [10.08, 277]; 14.23 [2.493, 84.02]; 4.169 [2.267, 7.871]; 5.44 [4.142, 7.238]; 8.731 [4.203, 19.29]; 7.306 [4.393, 13.04], respectively). At 52 weeks, compared to MTX alone, tocilizumab + MTX was significantly better for ACR20 and ACR50 response. Few significant differences were found between tocilizumab (alone or in combination) and any other biologics. Results must be considered in context with the limitations of the available evidence. This NMA suggests that tocilizumab was superior to cDMARDs and as effective as other biologics for RA.
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA. rafael.x.alfonso@gsk.com.
authors.forename: Rafael
authors.initials: R
authors.lastname: Alfonso-Cristancho
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Armstrong
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Arjunji
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.
authors.forename: Rob
authors.initials: R
authors.lastname: Riemsma
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.
authors.forename: Gill
authors.initials: G
authors.lastname: Worthy
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Ganguly
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.|School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Kleijnen
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000523:psychology; D001688:Biological Products / Q000627:therapeutic use*; D057186:Comparative Effectiveness Research; D004359:Drug Therapy, Combination; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D019947:Receptors, Interleukin-6; C502936:tocilizumab; D008727:Methotrexate
keywords: Anti-IL-6 receptor; Biologics; Disease-modifying agents for rheumatoid disease; Rheumatoid arthritis; Tocilizumab