title: Comparative efficacy of biologics as monotherapy and in combination with methotrexate on patient reported outcomes (PROs) in rheumatoid arthritis patients with an inadequate response to conventional DMARDs--a systematic review and network meta-analysis.
abstract: OBJECTIVE
  To compare biologics as monotherapy or in combination with methotrexate (MTX) in terms of patient reported outcomes (PROs) in RA patients with an inadequate response to conventional DMARDs (DMARD-IR).
  
  
  METHODS
  With a systematic literature review 17 RCTs were identified that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, abatacept, anakinra or tocilizumab. Treatment effects in terms of pain (0-100 mm), patient's global assessment of disease activity (PGA; 0-100 mm), Health Assessment-Questionnaire (HAQ) disability index (DI; 0-3), and the physical component summary (PCS) of the SF36 Health Survey (0-100) at 24 weeks were combined by means of Bayesian network meta-analyses.
  
  
  RESULTS
  With tocilizumab monotherapy, greater improvements in pain (difference = -11.1; (95% Credible Interval -21.3, -0.1)) and PGA (-10.3 (-20.4, 0.8)) were observed than with aTNF monotherapy. Tocilizumab was at least as efficacious as aTNF in HAQ-DI improvements (-0.16; (-0.37, 0.05)). aTNF + MTX (-17.9 (-23.1, -13.0) & -19.1 (-24.2, -14.4)), abatacept + MTX (-23.0 (-47.3, 1. 5) & -13.6 (-28.4, 2.0)) and tocilizumab + MTX (-16.0 (-26.3, -6.3) & -15.1 (-25.1, -5.7)) showed comparable reductions in pain and PGA relative to MTX. Efficacy of anakinra + MTX was much smaller as compared to other biologics. The greatest improvements in HAQ-DI relative to MTX were observed with aTNF + MTX (-0.30 (-0.37, -0.22)) and tocilizumab + MTX (-0.27 (-0.42, -0.12)), followed by abatacept + MTX (-0.21 (-0.37, -0.05)) and anakinra + MTX (-0.11 (-0.26, 0.05)). The improvements in SF36-PCS with abatacept + MTX, aTNF + MTX and tocilizumab + MTX were comparable. There is a >90% probability that aTNF + MTX results in a greater improvement in pain (-12.4), PGA (-16.1) and HAQ-DI (-0.21) than aTNF as monotherapy. Efficacy of tocilizumab + MTX showed comparable improvements in PROs as tocilizumab monotherapy.
  
  
  CONCLUSIONS
  Based on a network meta-analysis involving indirect comparison of trial findings, the following observations were made for DMARD-IR patients. In monotherapy, tocilizumab was associated with a greater improvement in pain and self-reported disease activity than aTNF, and was at least as efficacious regarding functional ability. The improvements in PROs with aTNF, abatacept and tocilizumab in combination with MTX were comparable. Improvements in PROs with tocilizumab as monotherapy were similar to that of tocilizumab + MTX, whereas aTNF as monotherapy was likely to be less efficacious than aTNF + MTX.
authors.forename: Jeroen P
authors.initials: JP
authors.lastname: Jansen
authors.affiliation: Mapi Group, 180 Canal Street, Suite 503, Boston, MA 02114, USA. fbuckley@mapigroup.com.
authors.forename: Felicity
authors.initials: F
authors.lastname: Buckley
authors.forename: Fred
authors.initials: F
authors.lastname: Dejonckheere
authors.forename: Sarika
authors.initials: S
authors.lastname: Ogale
mesh_terms: D000069594:Abatacept; D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D018771:Arthralgia / Q000188:drug therapy* / Q000209:etiology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D001499:Bayes Theorem; D001688:Biological Products / Q000627:therapeutic use; D000068582:Certolizumab Pegol; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011788:Quality of Life; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000069594:Abatacept; C529000:golimumab; D000069285:Infliximab; D000068879:Adalimumab; C502936:tocilizumab; D000068800:Etanercept; D000068582:Certolizumab Pegol; D008727:Methotrexate