Longterm effect of delaying combination therapy with tumor necrosis factor inhibitor in patients with aggressive early rheumatoid arthritis: 10-year efficacy and safety of adalimumab from the randomized controlled PREMIER trial with open-label extension

J Rheumatol. 2014 Jan;41(1):5-14. doi: 10.3899/jrheum.130543. Epub 2013 Nov 15.


Objective: To evaluate the longterm safety of adalimumab administered with or without methotrexate (MTX) and compare the efficacy of combination therapy initialization to adalimumab or MTX monotherapy initialization during the open-label extension (OLE) of the PREMIER trial (ClinicalTrials.gov Identifier:NCT00195663).

Methods: Patients with early rheumatoid arthritis (RA) were randomized to receive blinded adalimumab + MTX, adalimumab alone, or MTX alone for 2 years. Following the double-blinded period, patients enrolling in the OLE were given adalimumab for up to 8 additional years, beginning as monotherapy; investigators could add MTX at their discretion. Results for clinical, functional, and radiographic progression were collected for up to 10 years of treatment.

Results: During the PREMIER OLE, 250/497 patients (50.3%) completed the trial without new safety signals arising. Similar proportions of patients discontinued the trial early, although lack of efficacy was reported less often for patients initially randomized to the adalimumab + MTX arm (9.3%; 21.2%, and 23.7% for adalimumab and MTX monotherapies, respectively). Clinical and functional disease control was maintained throughout the trial. Patients initially randomized to adalimumab + MTX displayed better outcomes, particularly in prevention of radiographic progression (modified total Sharp score change = 4.0, 8.8, 11.0 at Year 10 for the initial adalimumab + MTX, adalimumab, and MTX arms, respectively).

Conclusion: Intensive therapy with adalimumab + MTX combination in patients with early RA has longterm benefits compared to patients initiating with 2-year adalimumab or MTX monotherapy that persists up to 10 years following adalimumab OLE. No new safety findings were observed following longterm adalimumab treatment.


Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / drug therapy*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Radiography
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Adalimumab
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT00195663