EXTENDED REPORT

¹ Charité – University Medicine Berlin, Berlin, Germany
² Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud 11, Le Kremlin Bicêtre, France
³ University of Pavia, IRCCS Policlinico San Matteo, Pavia, Italy
⁴ HGU Gregorio Marañón, Madrid, Spain
⁵ CHU Liège, Liège, Belgium
⁶ Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece
⁷ University Medical Center Utrecht, Utrecht, The Netherlands
⁸ Abbott GmbH & Co KG, Ludwigshafen, Germany

Correspondence to:
Dr Burmester
Department of Rheumatology and Clinical Immunology, Charité – University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; gerd.burmester{at}charite.de

Objective: To evaluate the safety and effectiveness of adalimumab alone or in combination with standard disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA).

Methods: Patients with active RA despite treatment with DMARDs or prior treatment with a tumour necrosis factor antagonist participated in a multicentre, open-label clinical study of adalimumab 40 mg every other week for 12 weeks with an optional extension phase. Patients were allowed to continue with pre-existing traditional DMARDs. Long-term safety results are reported for all patients (4210 patient-years (PYs) of adalimumab exposure). The observed effectiveness results at week 12 are reported using American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria.

Results: Among the 6610 treated patients, adalimumab was generally well tolerated. Serious infections occurred in 3.1% of patients (5.5/100 PYs, including active tuberculosis, 0.5/100 PYs). Demyelinating disease (0.06%) and systemic lupus erythematosus (0.03%) were rare serious adverse events. The standardised incidence ratio of malignancy was 0.71 (95% CI 0.49 to 1.01). The standardised mortality ratio was 1.07 (95% CI 0.75 to 1.49). At week 12, 69% of patients achieved an ACR20 response, 83% a moderate, and 33% a good EULAR response. Adalimumab was effective in combination with a variety of DMARDs. The addition of adalimumab to antimalarials was comparably effective to the combination of adalimumab and methotrexate.

Conclusions: Considering the limitations of an open-label study, adalimumab alone or in combination with standard DMARDs appeared to be well tolerated and effective in 6610 difficult-to-treat patients with active RA treated in clinical practice.

Abbreviations: ACR, American College of Rheumatology; AE, adverse event; AM, antimalarials; AZA, azathioprine; CsA, ciclosporin; DAS, Disease Activity Score; DMARD, disease-modifying antirheumatic drug; EULAR, European League Against Rheumatism; HAQ DI, Health Assessment Questionnaire Disability Index; LEF, leflunomide; MTX, methotrexate; PY, patient-year; RA, rheumatoid arthritis; SAE, serious adverse event; SEER, Surveillance, Epidemiology, and End Results; SIR, standardised incidence ratio; SSZ, sulfasalazine; TB, tuberculosis; TNF, tumour necrosis factor

Keywords: adalimumab; rheumatoid arthritis; tumour necrosis factor; monoclonal antibody; antirheumatic agents

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