EXTENDED REPORT

Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed

L B A van de Putte¹, C Atkins², M Malaise³, J Sany⁴, A S Russell⁵, P L C M van Riel¹, L Settas⁶, J W Bijlsma⁷, S Todesco⁸, M Dougados⁹, P Nash¹⁰, P Emery¹¹, N Walter¹², M Kaul¹², S Fischkoff¹³ and H Kupper¹²

¹ University of Nijmegen, The Netherlands
² Victoria, British Columbia, Canada
³ Service de Rhumatologie, Liege, Belgium
⁴ Hôpital Lapeyronie, Montpellier, France
⁵ University of Alberta Hospital, Edmonton, Alberta, Canada
⁶ AHEPA Hospital, Thessaloniki, Greece
⁷ UMC Utrecht, Utrecht, The Netherlands
⁸ Cattedra e Divisione di Reumatologia, Università di Padova, Padova, Italy
⁹ Service de Rhumatologie, Hôpital Cochin, Paris, France
¹⁰ Sixth Avenue Specialist Centre, Maroochydore, Australia
¹¹ University of Leeds, Leeds, UK
¹² Abbott GmbH & Co KG, Ludwigshafen, Germany
¹³ Abbott Laboratories, Parsippany, New Jersey, USA

Correspondence to:
Correspondence to:
Professor L B A van de Putte
University Medical Centre Nijmegen, Department of Rheumatology, PO Box 9101, 6500 HB Nijmegen, The Netherlands; annrheumdis.edoff{at}worldonline.nl

Objective: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed.

Methods: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was 20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI).

Results: After 26 weeks, patients treated with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, and 40 mg weekly had significantly better response rates than those treated with placebo: ACR20 (35.8%, 39.3%, 46.0%, 53.4%, respectively v 19.1%; p0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; p0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; p0.05). Moderate EULAR response rates were significantly greater with adalimumab than with placebo (41.5%, 48.2%, 55.8%, 63.1% v 26.4%; p0.05). Patients treated with adalimumab achieved better improvements in mean HAQ DI than those receiving placebo (–0.29, –0.39, –0.38, –0.49 v –0.07; p0.01). No significant differences were found between adalimumab and placebo treated patients for serious adverse events, serious infections, or malignancies. Injection site reaction occurred in 10.6% and 0.9% of adalimumab and placebo treated patients, respectively (p0.05).

Conclusion: Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.

Keywords: adalimumab; disease modifying antirheumatic drugs; human monoclonal antibodies; monotherapy; rheumatoid arthritis; tumour necrosis factor

Abbreviations: ACR, American College of Rheumatology; ANA, antinuclear antibody; CRP, C reactive protein; DAS, disease activity score; DMARDs, disease modifying antirheumatic drugs; ESR, erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; HAQ DI, Disability Index of the Health Assessment Questionnaire; MTX, methotrexate; NSAIDs, non-steroidal anti-inflammatory drugs; RA, rheumatoid arthritis; TNF, tumour necrosis factor

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