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Mycobacterial diseases and antitumour necrosis factor therapy in USA
  1. KL Winthrop1,3,
  2. R Baxter2,
  3. L Liu2,
  4. CD Varley1,
  5. JR Curtis4,
  6. JW Baddley4,
  7. B McFarland1,
  8. D Austin1,3,
  9. L Radcliffe3,
  10. EB Suhler1,3,
  11. D Choi1,
  12. JT Rosenbaum1,
  13. LJ Herrinton2
  1. 1Departments of Infectious Diseases (KLW), Public Health and Preventive Medicine (DC, KLW, DA), Ophthalmology (EBS, JTR, KLW, CDV), and Rheumatology (JTR), Oregon Health & Science University, Portland, Oregon
  2. 2Department of Infectious Diseases (RB), and Division of Research (LL, LJH), Kaiser Permanente Northern California, Oakland, California
  3. 3Portland Veteran's Affairs Medical Center (EBS,DA, LR), Portland, Oregon
  4. 4Departments of Infectious Diseases (JWB) and Rheumatology (JRC), University of Alabama Birmingham, Birmingham, Alabama
  1. Correspondence to Dr Kevin L Winthrop, Oregon Health Sciences University, 3375 SW Terwilliger Dr, Portland, Oregon, USA; winthrop{at}ohsu.edu

Abstract

Objective In North America, tuberculosis and nontuberculous mycobacterial (NTM) disease rates associated with antitumour necrosis factor α (anti-TNFα) therapy are unknown.

Methods At Kaiser Permanente Northern California, the authors searched automated pharmacy records to identify inflammatory disease patients who received anti-TNF therapy during 2000–2008 and used validated electronic search algorithms to identify NTM and tuberculosis cases occurring during anti-TNF drug exposure.

Results Of 8418 anti-TNF users identified, 60% had rheumatoid arthritis (RA). Among anti-TNF users, 18 developed NTM and 16 tuberculosis after drug start. Anti-TNF associated rates of NTM and tuberculosis were 74 (95% CI: 37 to 111) and 49 (95% CI: 18 to 79) per 100 000 person-years, respectively. Rates (per 100, 000 person-years) for NTM and tuberculosis respectively for etanercept were 35 (95% CI: 1 to 69) and 17 (95% CI: 0 to 41); infliximab, 116 (95% CI: 30 to 203) and 83 (95% CI: 10 to 156); and adalimumab, 122 (95% CI: 3 to 241) and 91 (95% CI: 19 to 267). Background rates for NTM and tuberculosis in unexposed RA-patients were 19.2 (14.2 to 25.0) and 8.7 (5.3 to 13.2), and in the general population were 4.1 (95% CI 3.9 to 4.4) and 2.8 (95% CI 2.6 to 3.0) per 100, 000 person-years. Among anti-TNF users, compared with uninfected individuals, NTM case-patients were older (median age 68 vs 50 years, p<0.01) and more likely to have RA (100% vs 60%, p<0.01); whereas, tuberculosis case-patients were more likely to have diabetes (37% vs 16%, p=0.02) or chronic renal disease (25% vs 6%, p=0.02).

Conclusions Among anti-TNF users in USA, mycobacterial disease rates are elevated, and NTM is associated with RA.

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Footnotes

  • Funding This work was funded by a grant from UCB pharmaceuticals. KL Winthrop's work on this manuscript was funded by an Agency for Healthcare Research and Quality (AHRQ) grant (1K08HS017552-01).

  • Competing interests KL Winthrop has received a grant from UCB pharmaceuticals and scientific advisory board fees from Amgen, Genentech, and Oxford Immunotech. JR Curtis has served as a consultant for Roche/Genentech, UCB, Centocor, CORRONA, Amgen, Pfizer, BMS, Crescendo and Abbott, and has received research support from Amgen, Roche/Genentech, Centocor and CORRONA. JW Baddley has served as a consultant for Abbott. EB Suhler has received research support from Abbott and Centocor. JT Rosenbaum consults for Amgen, Abbott, Centocor, and Genentech and has received grant support from Centocor, Genentech, and Abbott. LJ Herrinton has a research contract with Genentech and Proctor and Gamble

  • Provenance and peer review Not commissioned; externally peer reviewed.

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