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Case Reports of Heart Failure after Therapy with a Tumor Necrosis Factor Antagonist

Hyon J. Kwon, PharmD, MPH; Timothy R. Coté, MD, MPH; Michael S. Cuffe, MD; Judith M. Kramer, MD, MS; and M Miles Braun, MD, MPH

20 May 2003 | Volume 138 Issue 10 | Pages 807-811

Background: Etanercept and infliximab are U.S. Food and Drug Administration–approved tumor necrosis factor (TNF) antagonists.

Objective: To describe adverse event reports of heart failure after TNF antagonist therapy.

Design: Case series.

Setting: The U.S. Food and Drug Administration's MedWatch program.

Patients: 47 patients who developed new or worsening heart failure during TNF antagonist therapy.

Measurements: Clinical and laboratory reports.

Results: After TNF antagonist therapy, 38 patients developed new-onset heart failure and 9 patients experienced heart failure exacerbation. Of the 38 patients with new-onset heart failure, 19 (50%) had no identifiable risk factors. Ten patients younger than 50 years of age developed new-onset heart failure after receiving TNF antagonists. After TNF antagonist therapy was discontinued and heart failure therapy was started in these 10 patients, 3 had complete resolution of heart failure, 6 improved, and 1 died.

Conclusion: In a fraction of patients, TNF antagonists might induce new-onset heart failure or exacerbate existing disease.

Editors' Notes Context Although tumor necrosis factor (TNF) antagonists were once considered as a possible treatment for heart failure, recent trials showed no benefit, and one trial showed worsening heart failure with TNF antagonist treatment. Contribution This analysis of data from the U.S. Food and Drug Administration's MedWatch program on 47 patients who developed heart failure while receiving long-term TNF antagonist therapy showed that 81% had never experienced heart failure before taking TNF antagonists. Half of the patients with new-onset heart failure had no identifiable heart failure risk factors, and 10 patients were younger than 50 years of age. Implications Clinicians should be aware that heart failure may occur in patients receiving TNF antagonists. –The Editors

 

Author and Article Information

From the U.S. Food and Drug Administration, Rockville, Maryland, and Duke Clinical Research Institute, Durham, North Carolina.

Acknowledgments: The authors thank Ellis Unger, MD, and Jeffrey N. Siegel, MD, for their help and advice in reviewing the manuscript.

Grant Support: In part by Dr. Kwon's appointment to the Research Fellowship Program at the Center for Biologics Evaluation and Research, administered by Oak Ridge Associated Universities through a contract with the U.S. Food and Drug Administration.

Potential Financial Conflicts of Interest:Consultancies: M.S. Cuffe (Wyeth); Honoraria: M.S. Cuffe (Wyeth).

Requests for Single Reprints: Hyon J. Kwon, PharmD, MPH, Division of Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Suite 200S, HFM-224, Rockville, MD 20852; e-mail, kwon{at}cber.fda.gov.

Current Author Addresses: Drs. Kwon, Coté, and Braun: Division of Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Suite 200S, HFM-224, Rockville, MD 20852.

Dr. Cuffe: Duke University Medical Center, Box 3850, Durham, NC 27710.

Dr. Kramer: Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715.

Author Contributions: Conception and design: H.J. Kwon, M.S. Cuffe, M.M. Braun.

Analysis and interpretation of the data: H.J. Kwon, T.R. Coté, M.S. Cuffe, J.M. Kramer, M.M. Braun.

Drafting of the article: H.J. Kwon, M.S. Cuffe.

Critical revision of the article for important intellectual content: H.J. Kwon, T.R. Coté, M.S. Cuffe, J.M. Kramer, M.M. Braun.

Final approval of the article: H.J. Kwon, T.R. Coté, M.S. Cuffe, J.M. Kramer, M.M. Braun.

Administrative, technical, or logistic support: H.J. Kwon.

Collection and assembly of data: H.J. Kwon.

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Summaries for Patients
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