Efficacy, safety, and patient-reported outcomes of combination etanercept and sulfasalazine versus etanercept alone in patients with rheumatoid arthritis: a double-blind randomized two-year study

B. Combe ¹, C. Codreanu ², U. Fiocco ³, M. Gaubitz ⁴, P. P. Geusens ⁵, T. K. Kvien ⁶, K. Pavelka ⁷, P. N. Sambrook ⁸, J. S. Smolen ⁹, R. Khandker ¹⁰, A. Singh ¹⁰, J. Wajdula ^10* and S. Fatenejad ¹⁰

¹ Service d’Immuno-Rhumatologie, Hopital Lapeyronie, Montpellier, France
² Centrul Metodologic de Reumatologie, Bucuresti, Romania
³ Cattedra e Divisione di Reumatologia, Policlinico Universitario, Padova, Italy
⁴ Medical Clinic B Westfalian-Wilhelms-Univ, Munster, Germany
⁵ Biomedical Research Ctr, Univ Hasselt, Belgium & Dept of Internal Med/Rheum Univ Maastricht, Netherlands
⁶ Department of Rheumatology, Diakonhjemmets Hospital, Oslo, Norway
⁷ Institute of Rheumatology, Praha, Czech Republic
⁸ Kolling Institute, University of Sydney, Sydney, Australia
⁹ 2nd Dept of Med, Krankenhaus Lainz & Dept of Rheum, Internal Med II, Austria
¹⁰ Wyeth Research, Collegeville, Pennyslvania, United States

^* To whom correspondence should be addressed. E-mail: wajdulj{at}wyeth.com.

Accepted 18 August 2008

Abstract

Objective: To determine efficacy and safety of etanercept and etanercept+sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy.

Methods: Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept+sulfasalazine (unchanged regimen of 2-3 g/day) or sulfasalazine in a double-blind, randomised, 2-year study in adult patients with active RA despite sulfasalazine therapy. Efficacy was assessed using the American College of Rheumatology (ACR) criteria, disease activity scores (DAS), and patient-reported outcomes (PROs).

Results: Demographic variables and baseline disease characteristics were comparable among treatment groups; mean DAS was 5.1, 5.2 and 5.1, for etanercept (n=103), etanercept+sulfasalazine (n=101), and sulfasalazine (n=50) respectively. Withdrawal due to lack of efficacy was highest with sulfasalazine (26 [52%] versus 6 [6%] for either etanercept group, p<0.001). Patients receiving etanercept or etanercept+sulfasalazine had a more rapid initial response, which was sustained at 2 years, than those receiving sulfasalazine: mean DAS was 2.8, 2.5, versus 4.5 respectively (p<0.05); ACR 20 response was achieved by 67%, 77%, versus 34% of patients respectively (p<0.01) Overall, PROs followed a similar pattern; clinically significant improvement in Health Assessment Questionnaire was achieved by 76%, 78%, versus 40% of patients respectively (p<0.01). Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis (p<0.01).

Conclusion: Etanercept and etanercept+sulfasalazine are efficacious for the long-term management of patients with RA. Therefore, addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine.