The efficacy of anti-TNF in rheumatoid arthritis, a comparison between randomized controlled trials and clinical practice

W Kievit ^1*, J Fransen ¹, A JM Oerlemans ¹, H H Kuper ², M A.F.J. van de Laar ², DJ RAM de Rooij ³, C MA De Gendt ⁴, K H Ronday ⁵, T L Jansen ⁶, P CM van Oijen ⁷, H LM Brus ⁸, E M Adang ¹ and P LCM van Riel ¹

¹ Radboud University Nijmegen Medical Centre, Netherlands
² Medisch Spectrum Twente, Netherlands
³ Sint Maartenskliniek, Netherlands
⁴ Rijnstate Hospital, Netherlands
⁵ Leyenburg Hospital, Netherlands
⁶ Medical Center Leeuwarden, Netherlands
⁷ Jeroen Bosch Hospital, Netherlands
⁸ TweeSteden Hospital, Netherlands

^* To whom correspondence should be addressed. E-mail: w.kievit{at}reuma.umcn.nl.

Accepted 27 March 2007

Abstract

Background: Randomized controlled trials (RCT’s) evaluating the efficacy of antagonists to TNFá showed high response percentages in the groups treated with active drugs.

Objective: To compare the efficacy of anti-TNF treatments for Rheumatoid Arthritis (RA) patients in RCTs and in daily clinical practice, with an emphasis on the efficacy for patients eligible and non-eligible for RCT’s of anti-TNF treatments.

Methods: First, randomized placebo-controlled trials written in English for etanercept, infliximab and adalimumab for patients with RA were selected by a systematic review. Second, the DREAM (Dutch Rheumatoid Arthritis Monitoring) register with patients starting for the first time on one of the TNF-blocking agents was used. Patient characteristics, doses of medication and co-medication as well as the ACR20 response percentages were compared between RCTs and DREAM data, stratified for trial eligibility.

Results: In ten of eleven comparisons, the ACR20 response percentages were lower in daily clinical practice than in the RCT active drug group, which was significant in five of eleven comparisons. Only 34% to 79% of DREAM patients fulfilled the selection criteria for disease activity in the several RCTs. DREAM patients eligible for RCTs had higher response percentages then ineligible DREAM patients. ACR20 response percentages of eligible DREAM patients were comparable with the ACR20 response percentages of the RCT active drug group in ten of eleven comparisons.

Conclusion: The efficacy of TNF blocking agents in RCTs exceeded the efficacy of these drugs in clinical practice. However, in clinical practice more patients with lower disease activity were treated with TNF blocking agents compared with those treated in RCTs. For daily practice patients who were eligible for RCTs, responses were more similar to responses reached in RCT’s.

Keywords: bias, daily clinical practice, randomized controlled trials, rheumatoid arthritis

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