Two-Year Safety and Efficacy Experience in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis Treated with Etanercept and Conventional Disease-Modifying Anti-rheumatic Drugs in the Latin American Region

Daniel A. Machado1, Renato Guzman2, Ricardo M. Xavier3, *, Jesus A. Simon4, Linda Mele5, Qi Shen5, Ronald Pedersen5, Sameer Kotak5, Bonnie Vlahos5
1 CAICI Institute, Rosario, Santa Fe, Argentina
2 IDEARG; Saludcoop Clinic, Bogota, Colombia
3 Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
4 Universidad Marista de Mérida; BIOCEM/Hospital CEM, Mérida, Yucatán, Mexico
5 Pfizer, Collegeville, PA, USA

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Creative Commons License
© Machado et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at Rua Ramiro Barcelos, 2350, Sala 645, Porto Alegre/RS Brazil, 90035-903; Tel: 53-51-33598340; E-mail:



Although long-term data are available from biologic studies in North American/European populations with rheumatoid arthritis (RA), long-term findings in Latin American RA populations are limited.


To examine long-term safety/efficacy of etanercept, methotrexate, and/or other disease-modifying anti-rheumatic drugs (DMARDs) in Latin American patients with moderate-to-severe active RA.


In the first phase of this open-label study, patients were randomized to etanercept 50 mg weekly plus methotrexate or conventional DMARD (hydroxychloroquine or sulfasalazine) plus methotrexate for 24 weeks. At the start of the second phase (week 24), investigators selected a treatment regimen that included any combination/dosage of etanercept, methotrexate, hydroxychloroquine, or sulfasalazine based on previous treatment response, preference, and local product labeling, and was continued for the 104-week extension.


In the extension, in the group previously randomized to etanercept-plus-methotrexate therapy, etanercept was continued in 259/260 patients; methotrexate continued in 260/260; and hydroxychloroquine and sulfasalazine added in 8/260 and 3/260, respectively. In the group previously randomized to conventional DMARD-plus-methotrexate therapy, conventional DMARD was discontinued in 86/126 and etanercept added in 105/126. Among etanercept-exposed patients (total exposure, 798.1 patient-year [PY]), rates of adverse events, serious adverse events, and serious infections per PY were 1.7, 0.07, and 0.02 events per PY. In both groups, after treatment modification was permitted, clinical response rates and improvements in clinical/patient-reported outcomes from baseline were sustained to week 128.


After investigators were permitted to modify treatment, etanercept was part of the treatment regimen in 95% of patients. Continuation or addition of etanercept in the 2-year extension resulted in a consistently good risk:benefit profile.

Trial Registration:

Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy;, number NCT00848354;

Keywords: Disease-modifying antirheumatic drugs, etanercept, Latin America, methotrexate, rheumatoid arthritis.