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Extended report
The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis
  1. Kevin L Winthrop1,
  2. Joel Silverfield2,
  3. Arthur Racewicz3,
  4. Jeffrey Neal4,
  5. Eun Bong Lee5,
  6. Pawel Hrycaj6,
  7. Juan Gomez-Reino7,
  8. Koshika Soma8,
  9. Charles Mebus8,
  10. Bethanie Wilkinson8,
  11. Jennifer Hodge9,
  12. Haiyun Fan8,
  13. Tao Wang10,
  14. Clifton O Bingham III11
  1. 1Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA
  2. 2Department of Internal Medicine and Rheumatology, Healthpoint Medical Group, Tampa, Florida, USA
  3. 3Department of Rheumatology, Osteo-Medic s.c, Bialystok, Poland
  4. 4Department of Rheumatology, Bluegrass Community Research Inc., Lexington, Kentucky, USA
  5. 5Department of Internal Medicine, Seoul National University, Seoul, South Korea
  6. 6Department of Rheumatology and Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland
  7. 7Rheumatology Department, Hospital Clinico Universitario, Santiago de Compostela, Spain
  8. 8Department of Clinical Sciences, Pfizer Inc, Groton, Connecticut, USA
  9. 9Department of Inflammation, Pfizer Inc, New York, New York, USA
  10. 10Pfizer Inc, Shanghai, China
  11. 11Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  1. Correspondence to Dr Kevin L Winthrop, Casey Eye Institute, Oregon Health and Science University, 3375 SW Terwilliger Blvd, Portland, OR 97239, USA; Winthrop{at}


Objective To evaluate tofacitinib's effect upon pneumococcal and influenza vaccine immunogenicity.

Methods We conducted two studies in patients with rheumatoid arthritis using the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) and the 2011–2012 trivalent influenza vaccine. In study A, tofacitinib-naive patients were randomised to tofacitinib 10 mg twice daily or placebo, stratified by background methotrexate and vaccinated 4 weeks later. In study B, patients already receiving tofacitinib 10 mg twice daily (with or without methotrexate) were randomised into two groups: those continuing (‘continuous’) or interrupting (‘withdrawn’) tofacitinib for 2 weeks, and then vaccinated 1 week after randomisation. In both studies, titres were measured 35 days after vaccination. Primary endpoints were the proportion of patients achieving a satisfactory response to pneumococcus (twofold or more titre increase against six or more of 12 pneumococcal serotypes) and influenza (fourfold or more titre increase against two or more of three influenza antigens).

Results In study A (N=200), fewer tofacitinib patients (45.1%) developed satisfactory pneumococcal responses versus placebo (68.4%), and pneumococcal titres were lower with tofacitinib (particularly with methotrexate). Similar proportions of tofacitinib-treated and placebo-treated patients developed satisfactory influenza responses (56.9% and 62.2%, respectively), although fewer tofacitinib patients (76.5%) developed protective influenza titres (≥1:40 in two or more of three antigens) versus placebo (91.8%). In study B (N=183), similar proportions of continuous and withdrawn patients had satisfactory responses to PPSV-23 (75.0% and 84.6%, respectively) and influenza (66.3% and 63.7%, respectively).

Conclusions Among patients starting tofacitinib, diminished responsiveness to PPSV-23, but not influenza, was observed, particularly in those taking concomitant methotrexate. Among existing tofacitinib users, temporary drug discontinuation had limited effect upon influenza or PPSV-23 vaccine responses.

Trial registration numbers NCT01359150, NCT00413699.

  • Rheumatoid Arthritis
  • Vaccination
  • Infections

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See:

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