Ann Rheum Dis 62:1168-1177 doi:10.1136/ard.2003.009563
  • Extended report

Efficacy and safety of the fully human anti-tumour necrosis factor α monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis: a 12 week, phase II study

  1. L B A van de Putte1,
  2. R Rau2,
  3. F C Breedveld3,
  4. J R Kalden4,
  5. M G Malaise5,
  6. P L C M van Riel1,
  7. M Schattenkirchner6,
  8. P Emery7,
  9. G R Burmester8,
  10. H Zeidler9,
  11. H M Moutsopoulos10,
  12. K Beck11,
  13. H Kupper11
  1. 1University Hospital Nijmegen, Nijmegen, The Netherlands
  2. 2Rheumaklinik, Ratingen, Germany
  3. 3University of Leiden, Leiden, The Netherlands
  4. 4University of Erlangen, Erlangen, Germany
  5. 5University Hospital Liège, Liège, Belgium
  6. 6Universität München, München, Germany
  7. 7University of Leeds, Leeds, UK
  8. 8Universitätsklinikum Charité, Berlin, Germany
  9. 9Medizinische Hochschule Hannover, Hannover, Germany
  10. 10National and Kapodistrian University, Athens, Greece
  11. 11Abbott GmbH & Co. KG, Ludwigshafen, Germany
  1. Correspondence to:
    Professor L B A van de Putte
    University Medical Centre Nijmegen, Department of Rheumatology, PO Box 9101, 6500 HB Nijmegen, The Netherlands;
  • Accepted 28 July 2003


Objectives: To evaluate efficacy, dose response, safety, and tolerability of adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory patients with longstanding, active rheumatoid arthritis (RA).

Methods: During a 12 week, double blind, placebo controlled study, 284 patients were randomly allocated to receive weekly subcutaneous injections of adalimumab 20 mg (n = 72), 40 mg (n = 70), or 80 mg (n = 72) or placebo (n = 70) without concomitant DMARDs.

Results: Adalimumab significantly improved the signs and symptoms of RA for all efficacy measures. ACR20 responses with adalimumab were significant at each assessment versus placebo (p⩽0.01). Additionally, ACR responses with adalimumab were achieved more rapidly than with placebo, with 82/115 (71%) of the ultimate ACR20 response rate to adalimumab treatment achieved at week 2. At week 12, for adalimumab 20, 40, and 80 mg, ACR20 response rates were 50.7%, 57.1%, and 54.2%, respectively, versus 10.0% for placebo (p⩽0.001 for all comparisons); ACR50 rates were 23.9%, 27.1%, and 19.4%, respectively, versus 1.4% for placebo (p⩽0.001 for all comparisons); and ACR70 rates were 11.3%, 10.0%, and 8.3%, respectively, versus 0.0% for placebo (p⩽0.05 for all comparisons). All adalimumab doses significantly improved all ACR core criteria at all assessments. The 40 mg and 80 mg doses provided similar benefit. Adalimumab at all doses was generally well tolerated, with only mild or moderate adverse events. Completion rates were 87% for adalimumab and 67% for placebo.

Conclusions: Adalimumab given as monotreatment to patients with longstanding, severe RA refractory to traditional DMARDs produced a rapid, sustained response and was safe and well tolerated, with no dose limiting side effects.


  • Acting editor for this paper was Professor Frank Wollheim.