Effectiveness and safety of etanercept in subjects with RA who have failed infliximab therapy: 16-week, open-label, observational study

ABSTRACT

Background and objective: Tumor necrosis factor (TNF) antagonists, including etanercept (a soluble TNF receptor) and infliximab (an anti-TNF monoclonal antibody) are used in the treatment of patients with rheumatoid arthritis (RA). The purpose of this study was to evaluate the effectiveness and safety of 50 mg etanercept weekly in subjects with RA who have failed infliximab therapy.

Methods: This phase 4, multicenter, open-label, single-arm, 16-week observational study enrolled subjects who had experienced primary (failure to achieve an initial response) or secondary (failure to maintain an initial response) infliximab failures. Effectiveness was measured using European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) response criteria and laboratory assessments were used to evaluate levels of inflammation, lymphotoxin α, drug concentrations, and antibodies to infliximab. Safety endpoints included incidence of serious adverse events.

Results: At week 16, over half (62%; 95% CI = 55, 69) of all subjects in the trial achieved a good or moderate EULAR response (DAS28) with etanercept. Using ACR criteria, after 16 weeks of etanercept therapy, 45% (95% CI = 38, 52) of all subjects had achieved an ACR20 response. Benefits were noted in tender and swollen joint counts, subject and physician global assessments, joint pain, and the Health Assessment Questionnaire. Outcomes were similar between subjects with primary and secondary infliximab failures. Levels of lymphotoxin α did not appear to affect response to etanercept. Potential limitations included the lack of a washout period, short duration of the trial, and the number of subjects who did not receive all doses of etanercept.

Conclusion: In this open-label, uncontrolled study, subjects with moderate to severe RA who failed to respond or who lost their initial response to infliximab safely benefited from receiving etanercept.

Trial registration: ClinicalTrials.gov identifier: NCT00099554.

Key words: :

• Etanercept
• Infliximab
• Rheumatoid arthritis
• Switch
• TNF antagonist

Acknowledgments

Declaration of interest: This study was funded by Immunex Corporation, a wholly owned subsidiary of Amgen Inc., and by Wyeth Pharmaceuticals. The study sponsor was responsible for study design; collection, analysis, and interpretation of the data; writing of the paper; and decision to submit the manuscript for publication. The authors thank the EMBARK investigators, study coordinators, and patients who participated in this study. The authors also thank Yuling Wu, Lennie Uy, Binodh DeSilva, and Han Gunn of Amgen for performance of pharmacodynamic assays and JoAnn Tuan, Shelley Belouski, and Steve Swanson of Amgen for performance of the immunogenicity assays. Thanks also to Julia R. Gage, PhD, of Kendle International, Inc., for writing assistance on behalf of Amgen Inc. C.O.B. contributed to the study design, collection and interpretation of the data, and writing of the paper. A.I., B.H., and E.C.K. contributed to collection and interpretation of the data and critical review of the manuscript. Y.C. and S.B. contributed to the analysis and interpretation of the data and writing of the manuscript. All authors approved the final draft of the manuscript. C.O.B. is a clinical investigator, served as a consultant, and has received grant support from Amgen Inc. A.I., B.H., and E.C.K. have no competing interests. Y.C. and S.B. are employees of Amgen Inc.

Notes

* Manufactured by Immunex Corp., Thousand Oaks, CA and marketed by Amgen Inc., Thousand Oaks, CA and Wyeth Pharmeceuticals, Collegeville, PA

† Centocor, Inc., Malvern, PA

‡ Abbott Laboratories, North Chicago, IL