title: The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis.
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daily (with or without methotrexate) were randomised into two groups: those continuing ('continuous') or interrupting ('withdrawn') tofacitinib for 2 weeks, and then vaccinated 1 week after randomisation.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 In study B (N=183), similar proportions of continuous and withdrawn patients had satisfactory responses to PPSV-23 (75.0% and 84.6%, respectively) and influenza (66.3% and 63.7%, respectively).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.
  
  
  BACKGROUND
  NCT01359150, NCT00413699.
authors: Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA.
authors: Kevin L
authors: KL
authors: Winthrop
authors: Department of Internal Medicine and Rheumatology, Healthpoint Medical Group, Tampa, Florida, USA.
authors: Joel
authors: J
authors: Silverfield
authors: Department of Rheumatology, Osteo-Medic s.c, Bialystok, Poland.
authors: Arthur
authors: A
authors: Racewicz
authors: Department of Rheumatology, Bluegrass Community Research Inc., Lexington, Kentucky, USA.
authors: Jeffrey
authors: J
authors: Neal
authors: Department of Internal Medicine, Seoul National University, Seoul, South Korea.
authors: Eun Bong
authors: EB
authors: Lee
authors: Department of Rheumatology and Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland.
authors: Pawel
authors: P
authors: Hrycaj
authors: Rheumatology Department, Hospital Clinico Universitario, Santiago de Compostela, Spain.
authors: Juan
authors: J
authors: Gomez-Reino
authors: Department of Clinical Sciences, Pfizer Inc, Groton, Connecticut, USA.
authors: Koshika
authors: K
authors: Soma
authors: Department of Clinical Sciences, Pfizer Inc, Groton, Connecticut, USA.
authors: Charles
authors: C
authors: Mebus
authors: Department of Clinical Sciences, Pfizer Inc, Groton, Connecticut, USA.
authors: Bethanie
authors: B
authors: Wilkinson
authors: Department of Inflammation, Pfizer Inc, New York, New York, USA.
authors: Jennifer
authors: J
authors: Hodge
authors: Department of Clinical Sciences, Pfizer Inc, Groton, Connecticut, USA.
authors: Haiyun
authors: H
authors: Fan
authors: Pfizer Inc, Shanghai, China.
authors: Tao
authors: T
authors: Wang
authors: Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Clifton O
authors: CO
authors: Bingham
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007252:Influenza Vaccines / Q000276:immunology* / Q000627:therapeutic use; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011008:Pneumococcal Infections / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D007252:Influenza Vaccines; D010880:Piperidines; D022242:Pneumococcal Vaccines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D008727:Methotrexate
keywords: Infections; Rheumatoid Arthritis; Vaccination