Tumor necrosis factor alpha inhibitors, methotrexate or both? An inquiry into the formal evidence for when they are to be used in rheumatoid arthritis

Clin Exp Rheumatol. May-Jun 2008;26(3):449-52.


Objective: The relative high cost and potential side effects mandate careful scrutiny as to when tumor necrosis factor alpha (TNF) inhibitors should be used in everyday practice. We surveyed how TNF inhibitors performed in randomized controlled trials when compared to methotrexate in methotrexate naive rheumatoid arthritis patients.

Methods: We identified all randomized controlled trials with TNF inhibitors and methotrexate. We surveyed A-whether the patients enrolled were methotrexate naive or not; B-efficacy outcomes and C-radiographic outcomes.

Results: Four studies that had been reported to be conducted among metho-trexate naive patients were identified. TEMPO trial was not done entirely in methotrexate naive patients, contrary to what has been reported by its authors. Among these studies the methotrexate naive arms did as well as the TNF inhibitor alone. The combination was better than either drug alone. Among the 6 studies in which the methotrexate failure patients had been enrolled, the TNF inhibitors always performed better when analyzed head to head with the methotrexate alone arms.

Conclusions: Available data indicate that TNF inhibitors are superior to solo methotrexate use only in the setting of combination treatment.

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / drug therapy*
  • Drug Therapy, Combination
  • Etanercept
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Infliximab
  • Methotrexate / therapeutic use*
  • Radiography
  • Randomized Controlled Trials as Topic
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Etanercept
  • Methotrexate