Risk of tuberculosis among Alabama children and adolescents treated with tumor necrosis factor inhibitors: a retrospective study

Matthew L Stoll,Randy Q Cron,James Aaron Grubbs,Timothy Beukelman,Traci W Jester,Melissa L Mannion,Marilyn J Crain

doi:10.1186/s12969-017-0207-8

Abstract

BackgroundTumor Necrosis Factor inhibitors (TNFi) have dramatically improved the outlook for patients with inflammatory arthritides and bowel disease (IBD), but are associated with increased infection risks, including tuberculosis (TB). Pediatric inflammatory diseases are uncommon, and the risk of TB in children taking TNFi remains unclear. The objective of this study was to report the incidence of TB disease among TNFi recipients at a single pediatric medical center serving most of Alabama compared to that of the general population of Alabama children.MethodsInstances of TNFi usage among patients under age 20 years from July 1, 2007 through April 17, 2015 were captured from electronic health records at Children’s of Alabama (CoA), which has the only pediatric rheumatology clinic in Alabama, and where a substantial number of children in Alabama with inflammatory bowel disease receive care., and reports of TB cases were obtained from the Alabama Department of Public Health (ADPH). Incidence was expressed as TB cases/10,000 person-years, using population estimates from the Alabama Center for Health Statistics.Results1033 Alabama patients at CoA who were residents of Alabama were identified who received TNFi for a total of 1564 person-years. One adolescent on TNFi developed severe extrapulmonary TB (incidence density = 6.4 per 10,000; 95% CI 0.9–45.4 per 10,000). Sixty-three cases occurred in persons not on TNFi (incidence density = 0.064 per 10,000; 95% CI 0.050–0.082 per 10,000).ConclusionsOne case of TB disease among TNFi-exposed children was identified for 1564 person-years in Alabama residents. Although rare, this is higher than expected relative to the general rate of TB in Alabama. Thus, continued diagnostic vigilance for TB in children taking TNFi is required.Trial registration numberNot applicable.

Highlights

Tumor Necrosis Factor inhibitors (TNFi) have dramatically improved the outlook for patients with inflammatory arthritides and bowel disease (IBD), but are associated with increased infection risks, including tuberculosis (TB)
TNF is required for granuloma formation to contain Mycobacterium tuberculosis; impaired granuloma formation appears to be responsible for increased risk of disseminated infection [4]
The Swedish registry of adults with rheumatoid arthritis (RA) indicated a four-fold higher risk of active TB among TNFi users compared to non-users, compounded on the two-fold higher baseline risk in RA patients compared to the general population [6]

Summary

Introduction

Tumor Necrosis Factor inhibitors (TNFi) have dramatically improved the outlook for patients with inflammatory arthritides and bowel disease (IBD), but are associated with increased infection risks, including tuberculosis (TB). The objective of this study was to report the incidence of TB disease among TNFi recipients at a single pediatric medical center serving most of Alabama compared to that of the general population of Alabama children. Tumor Necrosis Factor inhibitors (TNFi) have revolutionized therapy for a variety of autoimmune conditions, including pediatric and adult arthritis and inflammatory bowel disease (IBD) [1]. A meta-analysis of infections in pediatric TNFi recipients reported 5 TB cases among 2949 patients with juvenile idiopathic arthritis (JIA) on TNFi and none among 1648 patients with inflammatory bowel disease (IBD), but no incidence rates could be calculated [7].

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