Tumour necrosis factor inhibitor monotherapy vs combination with MTX in the treatment of PsA: a systematic review of the literature

Rheumatology (Oxford). 2015 May;54(5):915-26. doi: 10.1093/rheumatology/keu415. Epub 2014 Oct 27.


Objectives: The aim of this study was to review the available evidence on TNF inhibitor monotherapy vs combination therapy with MTX in PsA.

Methods: A literature search was conducted up to and including October 2013 for randomized controlled trials (RCTs) and observational studies comparing TNF inhibitor monotherapy vs combination therapy with MTX in patients with PsA. Key information was extracted from the abstracts and/or full text of the articles retrieved.

Results: Eleven published articles and three conference abstracts were retrieved, reporting on six RCTs of four TNF inhibitors. Most RCTs found no differences in efficacy for peripheral arthritis between patients treated with or without MTX. However, the studies were not powered to answer this question. Some data suggest that concomitant MTX may reduce the progression of structural damage. No significant differences in other outcomes have been reported. Data on TNF inhibitor monotherapy vs MTX combination therapy were reported from six registries. Three registries reported that the use of concomitant MTX did not affect the efficacy of TNF inhibitor therapy. Data from three European Union registries suggest that TNF inhibitor (especially mAbs) drug survival is superior in patients taking concomitant MTX, while one Canadian registry reported no difference.

Conclusion: Available evidence on the efficacy and safety of TNF inhibitor monotherapy vs add-on MTX therapy shows little or no improvement with combination therapy, although the use of concomitant MTX appears to prolong TNF inhibitor drug survival of mAb TNF inhibitors. Registries and observational studies have the potential to fill some of the knowledge gaps in this area.

Keywords: TNF inhibitors; adalimumab; certolizumab pegol; etanercept; golimumab; infliximab; methotrexate; psoriatic arthritis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Psoriatic / drug therapy*
  • Biological Products / therapeutic use*
  • Canada
  • Drug Therapy, Combination
  • Europe
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Registries
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antirheumatic Agents
  • Biological Products
  • Tumor Necrosis Factor-alpha
  • Methotrexate