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The comparative risk of serious infections among rheumatoid arthritis patients starting or switching biological agents
  1. Jeffrey R Curtis1,2,
  2. Fenglong Xie1,
  3. Lang Chen1,
  4. John W Baddley1,
  5. Timothy Beukelman1,
  6. Kenneth G Saag1,2,
  7. Claire Spettell3,
  8. Raechele M McMahan4,
  9. Joaquim Fernandes3,
  10. Kevin Winthrop5,
  11. Elizabeth Delzell2
  1. 1Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  2. 2Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  3. 3Aetna Informatics, Aetna, Blue Bell, Pennsylvania, USA
  4. 4Aetna Specialty Pharmacy, Orlando, Florida, USA
  5. 5Oregon Health and Science University, Portland, Oregon, USA
  1. Correspondence to Jeffrey R Curtis, 510 20th Street South, FOT 805D, Birmingham, AL 35294, USA; jcurtis{at}


Background It is unclear whether anti-tumour necrosis factor alpha and biological agents with different mechanisms of action have similar safety. This study evaluated the incidence of hospitalised infections among rheumatoid arthritis (RA) patients starting or switching various biological agents.

Methods Using a database from a large US healthcare organisation from January 2005 to August 2009, the authors identified enrollees with RA and their treatment episodes entailing the new use of a biological agent, stratified by no biological use in the previous year (‘biological-free’) or switching from a different biological agent (‘switchers’). Outcomes were hospitalised infections identified using previously validated algorithms. Proportional hazards models estimated the hazard ratio of hospitalised infections, comparing each biological agent with infliximab.

Results Among 7847 biological treatment episodes, 63% were for biological-free patients and 37% for switchers. There were 364 hospitalised infections. Rates of hospitalised infection among biological-free patients and switchers were 4.6 and 7.0 per 100 person-years, respectively (p<0.0001). After multivariable adjustment controlling for biological-free/switcher status and other infection-related factors and compared with infliximab, users of abatacept (HR 0.68, 95% CI 0.48 to 0.96), adalimumab (HR 0.52, 0.39 to 0.71), etanercept (HR 0.64, 0.49 to 0.84) and rituximab (HR 0.81, 0.55 to 1.20) had lower rates of hospitalised infection. Patient risk factors contributed more to the risk of infection than did the risk associated with specific biological therapies.

Conclusion The rate of hospitalised infections among RA patients was highest for infliximab. Most of the variability in patients' risk of infection was driven by factors other than biological agent exposure.

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  • Funding This work was supported by the Agency for Healthcare Research and Quality (R01HS018517) and the Doris Duke Charitable Foundation. Some of the investigators receive support from the National Institutes of Health (AR053351).

  • Competing interests JRC: (research grants and consulting) UCB, Roche/Genentech, CORRONA, Centocor, Amgen, BMS, Abbott. ED: (research grants) Amgen. Remainder of co-authors: none.

  • Ethics approval This study was conducted with the approval of the University of Alabama at Birmingham institutional review board.

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

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