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Patient reported outcomes in a trial of combination therapy with etanercept and methotrexate for rheumatoid arthritis: the TEMPO trial
  1. D van der Heijde1,
  2. L Klareskog2,
  3. A Singh3,
  4. J Tornero4,
  5. J Melo-Gomes5,
  6. C Codreanu6,
  7. R Pedersen7,
  8. B Freundlich7,
  9. S Fatenejad8
  1. 1Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands
  2. 2Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden
  3. 3Global Health Outcomes Assessment, Wyeth Research, Collegeville, PA, USA
  4. 4Rheumatology, Hospital General de Guadalajara, Guadalajara, Spain
  5. 5Rheumatology, SERVIMED, Lisbon, Portugal
  6. 6Centrul de Boli Reumatismale, Bucuresti, Romania
  7. 7Global Medical Affairs, Wyeth Research, Collegeville, PA, USA
  8. 8Clinical Research and Development, Wyeth Research, Collegeville, PA, USA
  1. Correspondence to:
    Professor D van der Heijde
    Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands; dhe{at}


Objective: To compare patient reported measures of function, health related quality of life (QoL), and satisfaction with medication among patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), etanercept, or both for up to 1 year.

Methods: In a 52 week, double blind, clinical trial, patients with active RA were randomised to receive etanercept 25 mg twice weekly, methotrexate up to 20 mg weekly, or combination therapy. The Health Assessment Questionnaire (HAQ) disability index, EuroQoL health status visual analogue scale (EQ-5D VAS), patient global assessment, and patient general health VAS were administered at baseline and weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52. Satisfaction with the medication was compared at 52 weeks.

Results: Of 682 enrolled patients, 522 completed 52 weeks of treatment. Mean improvement from baseline in HAQ score was 0.65, 0.70, and 1.0 for MTX, etanercept, and the combination, respectively. The mean percentage and absolute improvement in the HAQ was significantly higher (p<0.01) for combination therapy than for either of the monotherapies. Combination therapy produced significantly more rapid achievement of HAQ ⩽0.5 sustained for 6 months than either of the monotherapies (p<0.01). Compared with patients receiving monotherapy, those receiving combination therapy achieved a significantly better (p<0.05) health state as measured by the EQ-5D VAS (mean (SD) 63.7 (3.2), 66.8 (3.2), 72.7 (3.1) for MTX, etanercept, and the combination, respectively). Results were similar for other assessments (p<0.01). Patients in combination and etanercept groups were significantly more likely (p<0.0001, p = 0.0009, respectively) to report satisfaction with the medication.

Conclusions: Combination therapy with etanercept and methotrexate improved function, QoL, and satisfaction with the medication significantly more than monotherapy.

  • ACR, American College of Rheumatology
  • AUC, area under the curve
  • CI, confidence interval
  • DAS, Disease Activity Score
  • DMARDs, disease modifying antirheumatic drugs
  • EQ-5D VAS, EuroQoL health status visual analogue scale
  • GHVAS, general health assessment on a visual analogue scale
  • HAQ, Health Assessment Questionnaire
  • LOCF, last observation carried forward
  • MTX, methotrexate
  • QoL, quality of life
  • PGAD, patient global assessment of disease activity
  • PRO, patient reported outcome
  • RA, rheumatoid arthritis
  • TEMPO, Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes
  • rheumatoid arthritis
  • etanercept
  • methotrexate
  • functional status
  • disability
  • patient outcome assessment
  • quality of life

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  • Published Online First 3 August 2005

  • Funding: Wyeth Research sponsored this trial as a post-approval commitment to the European Agency for the Evaluation of Medicinal Products. The sponsor was responsible for the collection and analysis of data. The authors and the sponsor were involved with study design, data interpretation, writing this article, and the decision to publish. The lead author and all other authors have had full access to the data and no restrictions on interpretation from the sponsor.

  • Competing interest statement: D van der Heijde has received reimbursement for symposium attendance and speaking and consulting fees from Wyeth, and has acted as an expert witness for Wyeth at an EMEA meeting for radiographic results of the TEMPO study. L Klareskog has received reimbursement for symposium attendance, speaking and consulting fees, and research funds from Wyeth. J Tornero has received reimbursement for symposium attendance, speaking fees, and research funds from Wyeth. J Melo-Gomes and C Codreanu declare no potential competing interests. A Singh, R Pedersen, B Freundlich, and S Fatenejad are employees of Wyeth and hold stock and/or stock options in Wyeth. B Freundlich has also received funds for research and staff members from Wyeth.

  • TEMPO study investigators: HD Bolosiu, Cluj-Napoca, Romania; P Bourgeois, Paris, France; J Cunha Branco, Lisbon, Portugal; J Braun, Herne, Germany; J Broell, Wien, Austria; G Bruyn, Leeuwarden, The Netherlands; J Brzezicki, Elblag, Poland; G Burmester, Berlin, Germany; B Canesi, Milano, Italy; A Cantagrel, Toulouse, France; X Chevalier, Creteil, France; H Chwalinska-Sadowska, Warszawa, Poland; L Cleland, Adelaide, Australia; C Codreanu, Bucuresti, Romania; L Coster, Linkoping, Sweden; M Cutolo, Genova, Italy; R Dahl, Uppsala, Sweden; P Dawes, Stoke-on-Trent, UK; J Dehais, Bordeaux, France; D Jan De Rooij, Nijmegen, The Netherlands; J P Devogelaer, Brussels, Belgium; D Doyle, London, UK; L Euller-Ziegler, Nice, France; F Fantini, Milano, Italy; G Ferraccioli, Udine, Italy; A Filipowicz-Sosnowska, Warszawa, Poland; S Freiseleben-Sorensen, Copenhagen, Denmark; P Geusens, Diepenbeek, Belgium; J Melo-Gomes, Lisbon, Portugal; JJ Gómez Reino, Santiago de Compostela, Spain; A Gough, Harrogate, UK; JP de Jager, Southport, Australia; M Janssen, Arnhem, Netherlands; H Julkunen, Vantaa, Finland; R Juvin, Grenoble, France; H Haentzschel, Leipzig, Germany; G Herrero-Beaumont, Madrid, Spain; W Hissink-Muller, Tilburg, Netherlands; J Kalden, Erlangen, Germany; C Kaufmann, Drammen, Norway; J Kekow, Vogelsang, Germany; L Klareskog, A Harju, Stockholm, Sweden; T Kvien, Oslo, Norway; A Laffón, Madrid, Spain; RBM Landewe, Maastricht, Netherlands; H Lang, Plauen, Germany; P Lanting, Doetinchem, Netherlands; X LeLoet, Rouen, France; B Lindell, Kalmar, Sweden; F Liote, Paris, France; R Luukkainen, Satalinna, Finland; M Malaise, Liege, Belgium; X Mariette, Le Kremlin Bicetre, France; E Martín Mola, Madrid, Spain; B Masek, Venlo, The Netherlands; Z Mencel, Kalisz, Poland; O Meyer, Paris, France; Y Molad, Petah-Tikva, Israel; C Montecucco, Pavia, Italy; R Myllykangas-Luosujarvi, Kuopio, Finland; H Nielsen, Herlev, Denmark; G Papadimitriou, Athens, Greece; K Pavelka, Prague, Czech Republic; A Perniok, Köln, Germany; F Radulescu, Bucuresti, Romania; V Rodriguez Valverde, Santander, Spain; A Rubinow, Jerusalem, Israel; P Sambrook, St Leonards, Australia; R Sanmartí, Barcelona, Spain; J Sany, Montpellier, France; A Saraux, Brest, France; M Schattenkirchner, Munchen, Germany; U Serni, Firenze, Italy; L Settas, Thessaloniki, Greece; J Sibilia, Strasbourg, France; H Stehlikova, Ceska Lipa, Czech Republic; J Szechinski, Wroclaw, Poland; J Szerla, Krakow, Poland; C Tanasescu, Bucuresti, Romania; H Tony, Wurzburg, Germany; J Tornero, Guadalajara, Spain; S Transo, Jonkoping, Sweden; F Trotta, Ferrara, Italy; T Tuomiranta, Tampere, Finland; E Veys, Gent, Belgium; G Valentini, Napoli, Italy; H van den Brink, Alkmaar, Netherlands; M van de Laar, Enschede, Netherlands; P Vitek, Zlin, Czech Republic; C Voudouris, Thessaloniki, Greece; R Westhovens, Leuven, Belgium.