Evaluation of two strategies (initial methotrexate monotherapy vs its combination with adalimumab) in management of early active rheumatoid arthritis: data from the GUEPARD trial

Rheumatology (Oxford). 2009 Nov;48(11):1429-34. doi: 10.1093/rheumatology/kep261. Epub 2009 Sep 9.

Abstract

Objectives: In early and active RA despite MTX, continuous treatment with TNF blockers in combination with MTX is recommended. To compare this strategy with an initial combination of MTX and adalimumab (ADA) given for 3 months and then adjusted based on the disease activity status.

Methods: Prospective unblinded randomized multicentre controlled 1-year trial in which 65 patients with early (<6 months) and active [disease activity score (DAS28(ESR)) >5.1] RA were assigned to Group 1 (32 patients): MTX (0.3 mg/kg/week, maximum of 20 mg/week, without escalating dose regimen) or to Group 2 (33 patients): initial combination therapy with MTX (as in Group 1) and ADA (40 mg eow). In both groups, treatment was adjusted every 3 months. The aim was to achieve a low DAS (DAS28(ESR) <3.2).

Results: From Week 12 until Week 52, seven patients in Group 1 and 11 patients in Group 2 remained in low disease activity state while receiving MTX monotherapy (P = 0.28). The 1-year area under the curve (AUC) of DAS28 was lower in Group 2 owing to an initial better response. The total intake of anti-TNF-alpha and the mean increase in total modified Sharp score was similar in the two groups.

Conclusions: Initial combination of MTX and ADA and then an adjusted based on the disease activity status achieved a faster control of disease activity but did not increase the number of patients for whom anti-TNF-alpha treatment was not needed after 12 weeks nor a better subsequent clinical or radiological outcome than a 3-month delayed initiation of anti-TNF in patients with still active disease despite MTX.

Publication types

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

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Prospective Studies
  • Radiography
  • Recovery of Function
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

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