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Therapies for Active Rheumatoid Arthritis after Methotrexate Failure

Open access
O'Dell, James R., Mikuls, Ted R., Taylor, Thomas H., Ahluwalia, Vandana, Brophy, Mary, Warren, Stuart R., Lew, Robert A., Cannella, Amy C., Kunkel, Gary, Phibbs, Ciaran S., Anis, Aslam H., Leatherman, Sarah, Keystone, Edward·2013·New England Journal of Medicine

Abstract

BACKGROUND: Few blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate--a common scenario in the management of rheumatoid arthritis. METHODS: We conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48. RESULTS: Both groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications. CONCLUSIONS: With respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275.)

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Metadata

Authors
O'Dell, J. R., Mikuls, T. R., Taylor, T. H., Ahluwalia, V., Brophy, M., Warren, S. R., Lew, R. A., Cannella, A. C., Kunkel, G., Phibbs, C. S., Anis, A. H., Leatherman, S., & Keystone, E.
Venue
New England Journal of Medicine
Published
2013-07-25
Volume
369
Issue
4
Pages
307-318
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
OpenAlex
W2164521956
Cited by
382
References
36
FWCI
36.58
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Therapies for Active Rheumatoid Arthritis after Methotrexate Failure. https://app.cochat.ai/papers/10.1056/nejmoa1303006
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O'Dell, J. R., Mikuls, T. R., Taylor, T. H., Ahluwalia, V., Brophy, M., Warren, S. R., Lew, R. A., Cannella, A. C., Kunkel, G., Phibbs, C. S., Anis, A. H., Leatherman, S., & Keystone, E. (2013). Therapies for Active Rheumatoid Arthritis after Methotrexate Failure. New England Journal of Medicine. https://doi.org/10.1056/nejmoa1303006

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