The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis

Kevin L. Winthrop, Joel Silverfield, Arthur Racewicz, Jeffrey Neal, Eun Bong Lee, Pawel Hrycaj, Juan Gomez-Reino, Koshika Soma, Charles Mebus, Bethanie Wilkinson, Jennifer Hodge, Haiyun Fan, Tao Wang, Clifton Bingham

Research output: Contribution to journalArticle

Abstract

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daily (with or without methotrexate) were randomised into two groups: those continuing ('continuous') or interrupting ('withdrawn') tofacitinib for 2 weeks, and then vaccinated 1 week after randomisation.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 In study B (N=183), similar proportions of continuous and withdrawn patients had satisfactory responses to PPSV-23 (75.0% and 84.6%, respectively) and influenza (66.3% and 63.7%, respectively).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.

Original languageEnglish (US)
JournalAnnals of the Rheumatic Diseases
DOIs
StateAccepted/In press - Mar 20 2015

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Pneumococcal Vaccines
Influenza Vaccines
Rheumatoid Arthritis
Human Influenza
Methotrexate
Placebos
tofacitinib
Antigens
Random Allocation
Streptococcus pneumoniae
Drug Users
Vaccination
Vaccines

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

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The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. / Winthrop, Kevin L.; Silverfield, Joel; Racewicz, Arthur; Neal, Jeffrey; Lee, Eun Bong; Hrycaj, Pawel; Gomez-Reino, Juan; Soma, Koshika; Mebus, Charles; Wilkinson, Bethanie; Hodge, Jennifer; Fan, Haiyun; Wang, Tao; Bingham, Clifton.

In: Annals of the Rheumatic Diseases, 20.03.2015.

Research output: Contribution to journalArticle

Winthrop, KL, Silverfield, J, Racewicz, A, Neal, J, Lee, EB, Hrycaj, P, Gomez-Reino, J, Soma, K, Mebus, C, Wilkinson, B, Hodge, J, Fan, H, Wang, T & Bingham, C 2015, 'The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis', Annals of the Rheumatic Diseases. https://doi.org/10.1136/annrheumdis-2014-207191
Winthrop, Kevin L. ; Silverfield, Joel ; Racewicz, Arthur ; Neal, Jeffrey ; Lee, Eun Bong ; Hrycaj, Pawel ; Gomez-Reino, Juan ; Soma, Koshika ; Mebus, Charles ; Wilkinson, Bethanie ; Hodge, Jennifer ; Fan, Haiyun ; Wang, Tao ; Bingham, Clifton. / The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. In: Annals of the Rheumatic Diseases. 2015.
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abstract = "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.",
author = "Winthrop, {Kevin L.} and Joel Silverfield and Arthur Racewicz and Jeffrey Neal and Lee, {Eun Bong} and Pawel Hrycaj and Juan Gomez-Reino and Koshika Soma and Charles Mebus and Bethanie Wilkinson and Jennifer Hodge and Haiyun Fan and Tao Wang and Clifton Bingham",
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AU - Silverfield, Joel

AU - Racewicz, Arthur

AU - Neal, Jeffrey

AU - Lee, Eun Bong

AU - Hrycaj, Pawel

AU - Gomez-Reino, Juan

AU - Soma, Koshika

AU - Mebus, Charles

AU - Wilkinson, Bethanie

AU - Hodge, Jennifer

AU - Fan, Haiyun

AU - Wang, Tao

AU - Bingham, Clifton

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N2 - 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.

AB - 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.

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