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Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis
  1. Jeffrey R Curtis1,2,
  2. Fenglong Xie1,
  3. Huifeng Yun1,2,
  4. Sasha Bernatsky3,
  5. Kevin L Winthrop4
  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. 3Division of Clinical Epidemiology McGill University Health Centre, Montreal, Quebec, Canada
  4. 4Divisions of Infectious Diseases, Public Health, and Preventive Medicine, Oregon Health & Science University, Portland, Oregon, USA
  1. Correspondence to Dr Jeffrey R Curtis, FOT 802, 510 20th Street South, Birmingham 35294, USA; jcurtis{at}


Objective To evaluate the risks of herpes zoster (HZ) and herpes simplex virus (HSV) infection associated with tofacitinib compared with biologic agents among patients with rheumatoid arthritis (RA).

Methods Using health plan data from 2010 to 2014, patients with RA initiating tofacitinib or biologics with no history of HZ or HSV were identified, as were incident cases of HZ or HSV. Crude incidence rates were calculated by drug exposure. Cox proportional hazards models evaluated the adjusted association between tofacitinib and HZ, and a composite outcome of HZ or HSV.

Results A total of 2526 patients initiating tofacitinib were compared with initiations of other biologics: anti-tumour necrosis factor (TNF) (n=42 850), abatacept (n=12 305), rituximab (n=5078) and tocilizumab (n=6967). Patients receiving tofacitinib were somewhat younger (mean age 55 years) versus those on other biologics, and somewhat less likely to use concomitant methotrexate (MTX) (39% vs 43%–56%, depending on drug). Crude incidence of HZ associated with tofacitinib was 3.87/100 patient-years (py). After multivariable adjustment, HZ risk was significantly elevated, HR 2.01 (95% CI 1.40 to 2.88) compared with abatacept. Rates and adjusted HRs for all other RA biologics were comparable with each other and abatacept. Older age, female sex, prednisone >7.5 mg/day, prior outpatient infection and greater number of hospitalisations were also associated with increased HZ risk. Incidence rates for the combined outcome were greatest for tofacitinib (7.61/100 py) and also significantly elevated after adjustment (HR=1.40, 95% CI 1.09 to 1.81).

Conclusions The rate of zoster associated with tofacitinib was approximately double that observed in patients using biologics.

  • Infections
  • Rheumatoid Arthritis
  • Vaccination

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