title: What drives the comparative effectiveness of biologics vs. methotrexate in rheumatoid arthritis? Meta-regression and graphical inspection of suspected clinical factors.
abstract: OBJECTIVE
  The aim of this study was to explore which clinical factors and patient characteristics are associated with the magnitude of comparative efficacy between biologics vs. MTX in RA patients with inadequate response to MTX.
  
  
  METHODS
  We included randomized controlled trials assessing the efficacy of a biologic plus MTX vs. MTX alone. We examined several clinical factors and patient characteristics potentially associated with magnitude of response, measured as ACR20 (20% improvement in ACR criteria) and ACR50 (16-26 weeks). We employed meta-regression for formal estimates and statistical significance of effect modification. We produced regression and forest plots to further inspect potential associations.
  
  
  RESULTS
  For ACR50, a 1-year increment on the average patient disease duration was statistically significantly associated with a 16% relative increase in the pooled odds ratio (OR) estimate (P = 0.003). A 1-year increment in patient age and a 1 mg/week increment in MTX dose were marginally statistically significantly associated with a 9% (P = 0.056) and 22% (P = 0.092) relative increase in the OR. For ACR20, the average number of swollen and tender joints was marginally statistically associated with a 3% relative decrease. The associations for age and MTX dose appeared to be partly driven by significant negative associations between these two factors and the control group response.
  
  
  CONCLUSIONS
  Our analyses identified key variables associated with the magnitude of comparative effects for ACR outcomes. Our findings provide valuable insights for future trial designs and systematic reviews as well as decision-making and clinical practice.
authors.affiliation: Department of Population and Public Health, University of British Columbia, Vancouver, BC, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, Stanford Prevention Research Center, Stanford University, Palo Alto, CA, USA and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.Department of Population and Public Health, University of British Columbia, Vancouver, BC, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, Stanford Prevention Research Center, Stanford University, Palo Alto, CA, USA and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Kanters
authors.affiliation: Department of Population and Public Health, University of British Columbia, Vancouver, BC, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, Stanford Prevention Research Center, Stanford University, Palo Alto, CA, USA and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Druyts
authors.affiliation: Department of Population and Public Health, University of British Columbia, Vancouver, BC, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, Stanford Prevention Research Center, Stanford University, Palo Alto, CA, USA and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.Department of Population and Public Health, University of British Columbia, Vancouver, BC, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, Stanford Prevention Research Center, Stanford University, Palo Alto, CA, USA and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Mills
authors.affiliation: Department of Population and Public Health, University of British Columbia, Vancouver, BC, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, Stanford Prevention Research Center, Stanford University, Palo Alto, CA, USA and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.Department of Population and Public Health, University of British Columbia, Vancouver, BC, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, Stanford Prevention Research Center, Stanford University, Palo Alto, CA, USA and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. thorluk@mcmaster.ca.
authors.forename: Kristian
authors.initials: K
authors.lastname: Thorlund
mesh_terms: D000305:Adrenal Cortex Hormones; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use*; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D001688:Biological Products; D008727:Methotrexate
keywords: biologics; comparative efficacy; effect modifiers; indirect treatment comparison; meta-analysis; meta-regression; rheumatoid arthritis