Brief Communication: Characteristics of Spontaneous Cases of Tuberculosis Associated with Infliximab

20 November 2007 | Volume 147 Issue 10 | Pages 699-702

Background: A warning for tuberculosis was added to the approved labeling for infliximab in October 2001.

Objective: To describe adverse event reports of tuberculosis during infliximab therapy after labeling changes.

Design: Case series.

Setting: Spontaneous adverse event reports maintained in the Adverse Event Reporting System database in the United States.

Patients: 130 patients with infliximab-associated tuberculosis.

Measurements: Clinical and laboratory data.

Results: The U.S. Food and Drug Administration received 130 domestic, spontaneous reports of tuberculosis in patients treated with infliximab between 1 November 2001 and 30 May 2006, including 59 (45%) with extrapulmonary disease. The most commonly reported risk factors included concomitant immunosuppressant use (n = 89), history of latent or active tuberculosis (n = 33), and being born into or having spent extensive time in an area where tuberculosis is endemic (n = 25). In the subset of 67 cases with documented initiation of infliximab therapy after the drug labeling change, 34 patients with a negative tuberculin skin test result before initiation of infliximab therapy developed tuberculosis after receiving infliximab.

Limitation: Conclusions from spontaneous case reports may not be generalizable to the entire infliximab-receiving population.

Conclusion: Clinicians should be vigilant in screening and monitoring for tuberculosis in patients receiving infliximab.

Editors' Notes Context In October 2001, the U.S. Food and Drug Administration (FDA) modified infliximab labeling to include a boxed warning about infliximab-associated tuberculosis that included instructions to screen for tuberculosis, treat latent tuberculosis before treatment, and monitor for tuberculosis during infliximab therapy. Contribution This series reviewed 130 cases of infliximab-associated tuberculosis reported to the FDA after the labeling change and found that many cases occurred in patients who had a negative tuberculin skin test result but had risk factors for tuberculosis. Implication Clinicians need to be vigilant for tuberculosis in patients receiving infliximab even if pretreatment screening is negative, especially if risk factors for tuberculosis are present. —The Editors

 

Author and Article Information

From the U. S. Food and Drug Administration, Silver Spring, Maryland.

Disclaimer: The views expressed are those of the authors and do not necessarily represent those of, nor imply endorsement from, the U.S. Food and Drug Administration or the U.S. government.

Acknowledgment: The authors thank Dr. Gerald Dal Pan, Office of Surveillance and Epidemiology, for his thoughtful review and critique of the manuscript.

Potential Financial Conflicts of Interest: None disclosed.

Reproducible Research Statement: The protocol is provided in the text of the article and was not prospectively designed for this specific case series. An overview of the history and treatment of adverse drug event reports (MedWatch reports) at the FDA's Center for Drug Evaluation and Research is included in the paper by Brinker and Beitz (7). No statistical models or code were used. Because of the presence of personal and confidential information, the MedWatch cases included in this case series are not available to the general public. Aggregated and truncated MedWatch reports by calendar year with redaction of personal identifiers are available for purchase as electronic data sets from the National Technical Information Service (http://www.ntis.gov).

Requests for Single Reprints: Gita Akhavan-Toyserkani, PharmD, MBA, Office of Surveillance and Epidemiology, Division of Drug Risk Evaluation, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Building 22, Room 3469, Silver Spring, MD 20993.

Current Author Addresses: Dr. Raval: 7272 Wisconsin Avenue, Bethesda, MD 20814.

Drs. Akhavan-Toyserkani, Brinker, and Avigan: Office of Surveillance and Epidemiology, Division of Drug Risk Evaluation, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Building 22, Silver Spring, MD 20993.

Author Contributions: Conception and design: A. Raval, G. Akhavan-Toyserkani, M. Avigan.

Analysis and interpretation of the data: A. Raval, G. Akhavan-Toyserkani, A. Brinker, M. Avigan.

Drafting of the article: A. Raval, G. Akhavan-Toyserkani, A. Brinker, M. Avigan.

Critical revision of the article for important intellectual content: A. Raval, G. Akhavan-Toyserkani, A. Brinker, M. Avigan.

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