OBJECTIVES: All biologic agents approved for the treatment of rheumatoid arthritis (RA) have been tested versus methotrexate (MTX) for efficacy on damage progression in several randomized clinical trials (RCTs), but direct head-to-head comparisons have never been conducted. The purpose of this investigation is to analyse data coming from main RA RCTs and to perform an indirect comparison. METHODS: A systematic review of literature from 1988 to 2011 was conducted. Only randomized, double-blind, controlled, comparative trials, with evaluation of radiographic progression were included. The radiographic score was standardized and mean difference in the percentage of the annual radiographic progression rate was used as the effect measure. Heterogeneity between studies was estimated by I(2) test. For each trial, the effect was plotted according to its standard error in a funnel plot. RESULTS: Of 44 potentially relevant trials, 12 RCTs were included in the study. In order to optimize RCTs comparison, studies were stratified in early and late RA group. Main population characteristics were similar in both early and late RA groups, whereas the standardized baseline radiographic score value significantly differs among trials in both early (range 2.7-21.9) and late (range 23.46-75) RA groups. The standardized annual estimated progression is similar across the late RA group. Strong evidence of heterogeneity (I(2) = 97%, p = 0.00001) but no asymmetry of the funnel plot was observed in the early RA group. Total mean difference was -16.28 (95% confidence interval [CI] -24.42 to -8.14). For the late RA group a random model was used (I(2) = 99%, p = 0.00001) and a total mean difference of -39.25 (95% CI -53.77 to -24.73) was found. CONCLUSIONS: All biologic agents provide a favourable effect on disease progression both in early and late RA. The significant heterogeneity among various RCTs did not allow an effective comparison of the performance of biologic agents in each study.
OBJECTIVES: All biologic agents approved for the treatment of rheumatoid arthritis (RA) have been tested versus methotrexate (MTX) for efficacy on damage progression in several randomized clinical trials (RCTs), but direct head-to-head comparisons have never been conducted. The purpose of this investigation is to analyse data coming from main RA RCTs and to perform an indirect comparison. METHODS: A systematic review of literature from 1988 to 2011 was conducted. Only randomized, double-blind, controlled, comparative trials, with evaluation of radiographic progression were included. The radiographic score was standardized and mean difference in the percentage of the annual radiographic progression rate was used as the effect measure. Heterogeneity between studies was estimated by I(2) test. For each trial, the effect was plotted according to its standard error in a funnel plot. RESULTS: Of 44 potentially relevant trials, 12 RCTs were included in the study. In order to optimize RCTs comparison, studies were stratified in early and late RA group. Main population characteristics were similar in both early and late RA groups, whereas the standardized baseline radiographic score value significantly differs among trials in both early (range 2.7-21.9) and late (range 23.46-75) RA groups. The standardized annual estimated progression is similar across the late RA group. Strong evidence of heterogeneity (I(2) = 97%, p = 0.00001) but no asymmetry of the funnel plot was observed in the early RA group. Total mean difference was -16.28 (95% confidence interval [CI] -24.42 to -8.14). For the late RA group a random model was used (I(2) = 99%, p = 0.00001) and a total mean difference of -39.25 (95% CI -53.77 to -24.73) was found. CONCLUSIONS: All biologic agents provide a favourable effect on disease progression both in early and late RA. The significant heterogeneity among various RCTs did not allow an effective comparison of the performance of biologic agents in each study.
Authors: P E Lipsky; D M van der Heijde; E W St Clair; D E Furst; F C Breedveld; J R Kalden; J S Smolen; M Weisman; P Emery; M Feldmann; G R Harriman; R N Maini Journal: N Engl J Med Date: 2000-11-30 Impact factor: 91.245
Authors: Robert B M Landewé; Maarten Boers; Arco C Verhoeven; Rene Westhovens; Mart A F J van de Laar; Harry M Markusse; J Christiaan van Denderen; Marie Louise Westedt; Andre J Peeters; Ben A C Dijkmans; Piet Jacobs; Annelies Boonen; Désirée M F M van der Heijde; Sjef van der Linden Journal: Arthritis Rheum Date: 2002-02
Authors: Y P M Goekoop-Ruiterman; J K de Vries-Bouwstra; C F Allaart; D van Zeben; P J S M Kerstens; J M W Hazes; A H Zwinderman; H K Ronday; K H Han; M L Westedt; A H Gerards; J H L M van Groenendael; W F Lems; M V van Krugten; F C Breedveld; B A C Dijkmans Journal: Arthritis Rheum Date: 2005-11
Authors: Joel M Kremer; Harry K Genant; Larry W Moreland; Anthony S Russell; Paul Emery; Carlos Abud-Mendoza; Jacek Szechinski; Tracy Li; Zhiyu Ge; Jean-Claude Becker; Rene Westhovens Journal: Ann Intern Med Date: 2006-06-20 Impact factor: 25.391
Authors: Mark C Genovese; Joan M Bathon; Richard W Martin; Roy M Fleischmann; John R Tesser; Michael H Schiff; Edward C Keystone; Mary Chester Wasko; Larry W Moreland; Arthur L Weaver; Joseph Markenson; Grant W Cannon; George Spencer-Green; Barbara K Finck Journal: Arthritis Rheum Date: 2002-06
Authors: Paul Emery; Roy Fleischmann; Désirée van der Heijde; Edward C Keystone; Mark C Genovese; Philip G Conaghan; Elizabeth C Hsia; Weichun Xu; Anna Baratelle; Anna Beutler; Mahboob U Rahman Journal: Arthritis Rheum Date: 2011-05
Authors: Joel M Kremer; Anthony S Russell; Paul Emery; Carlos Abud-Mendoza; Jacek Szechinski; Rene Westhovens; Tracy Li; Xianhuang Zhou; Jean-Claude Becker; Richard Aranda; Charles Peterfy; Harry K Genant Journal: Ann Rheum Dis Date: 2011-10 Impact factor: 19.103
Authors: P Emery; P Durez; M Dougados; C W Legerton; J-C Becker; G Vratsanos; H K Genant; C Peterfy; P Mitra; S Overfield; K Qi; R Westhovens Journal: Ann Rheum Dis Date: 2009-11-23 Impact factor: 19.103
Authors: Edward Keystone; Désireé van der Heijde; David Mason; Robert Landewé; Ronald Van Vollenhoven; Bernard Combe; Paul Emery; Vibeke Strand; Philip Mease; Chintu Desai; Karel Pavelka Journal: Arthritis Rheum Date: 2008-11
Authors: E Bizzi; U Massafra; B Laganà; V Bruzzese; A Picchianti Diamanti; M Cassol; A Migliore Journal: Clin Rheumatol Date: 2014-02-08 Impact factor: 2.980