The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis
Open accessAbstract
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daily (with or without methotrexate) were randomised into two groups: those continuing ('continuous') or interrupting ('withdrawn') tofacitinib for 2 weeks, and then vaccinated 1 week after randomisation.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 In study B (N=183), similar proportions of continuous and withdrawn patients had satisfactory responses to PPSV-23 (75.0% and 84.6%, respectively) and influenza (66.3% and 63.7%, respectively).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.
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In RA patients, tofacitinib produced a considerable influenza vaccine response but an impaired pneumococcal vaccine response, especially with MTX.
“Limited data regarding other vaccines have shown that patients with RA treated with tofacitinib achieved a considerable response to influenza vaccine but an impaired response to a pneumococcal vaccine, especially when combined with MTX.32”
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- Authors
- Winthrop, K. L., Silverfield, J., Racewicz, A., Neal, J., Lee, E. B., Hrycaj, P., Gomez-Reino, J., Soma, K., Mebus, C., Wilkinson, B., Hodge, J., Fan, H., Wang, T., & Bingham, C. O.
- Affiliations
- Oregon Health & Science University (US)
- Healthpoint (AE)
- Seoul National University (KR)
- Pfizer (United States) (US)
- Johns Hopkins University (US)
- Corresponding author
- Winthrop, Kevin L
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 75
- Issue
- 4
- Pages
- 687-695
- ISSN
- 0003-4967 (ISSN-L)
- PMC
- PMC4819610
- OpenAlex
- W2097302763
- Cited by
- 196
- References
- 47
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 11 · 2023: 18 · 2022: 27 · 2021: 49 · 2020: 20 · 2019: 13 · 2018: 16 · 2017: 20 · 2016: 7 · 2015: 3
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of the Rheumatic Diseases (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- tofacitinib, rheumatoid arthritis, pneumococcal polysaccharide vaccine, influenza vaccination, vaccine immunogenicity, JAK inhibitors, methotrexate, drug discontinuation, antibody titers
- MeSH terms
- Adult, Aged, Aged, 80 and over, Arthritis, Rheumatoid, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Immunosuppressive Agents, Influenza, Human, Influenza Vaccines, Male, Methotrexate, Middle Aged, Piperidines, Pneumococcal Infections, Pyrimidines, Pyrroles, Immunocompromised Host, Pneumococcal Vaccines, Protein Kinase Inhibitors, Young Adult
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