title: Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor.
abstract: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The implications of treatment with tofacitinib on cardiovascular (CV) risk in RA are unknown. Therefore, CV adverse events (AEs), and blood pressure and lipid level changes, in tofacitinib-treated patients with RA were evaluated.
  
  
  
  Data were pooled from six Phase (P)3 studies (24 months) and two open-label long-term extension (LTE) studies (60 months) of tofacitinib in patients with RA and inadequate response to DMARDs. Tofacitinib was administered alone or with non-biologic DMARDs. CV events, including major adverse CV events (MACE: CV death and non-fatal CV events) and congestive heart failure (CHF), were assessed by a blinded adjudication committee.
  
  
  
  Overall, 4271 patients from P3 studies and 4827 enrolled from P2/P3 studies into LTE studies were evaluated, representing 3942 and 8699 patient-years of exposure to tofacitinib, respectively. Blood pressure remained stable over time across studies. The number of investigator-reported hypertension-related AEs in tofacitinib-treated patients was low in P3 studies (Months 0-3: 2.8%; Months 3-6: 1.4%; >6 months: 2.8%). Across studies, lipid level increases were generally observed within 1-3 months of treatment and stabilized thereafter. Patients with events (incidence rate [IR]/100 patient-years) for MACE and CHF, respectively, were: 23 (0.58) and 9 (0.23) in P3 studies, and 32 (0.37) and 8 (0.09) in LTE studies; IRs were comparable with placebo (P3) and did not increase over time (LTE).
  
  
  
  Tofacitinib was associated with a low incidence of CV events in a large Phase 3 program, including LTE studies. Further long-term studies are underway.
authors.affiliation: University of California, Los Angeles, CA. Electronic address: ccharles@mednet.ucla.edu.
authors.forename: Christina
authors.initials: C
authors.lastname: Charles-Schoeman
authors.affiliation: PW Consulting LLC, Mystic, CT.
authors.forename: Pierre
authors.initials: P
authors.lastname: Wicker
authors.affiliation: Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gonzalez-Gay
authors.affiliation: Pfizer Inc., Groton, CT.
authors.forename: Mary
authors.initials: M
authors.lastname: Boy
authors.affiliation: Pfizer Inc., New London, CT.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zuckerman
authors.affiliation: Pfizer Inc., Groton, CT.
authors.forename: Koshika
authors.initials: K
authors.lastname: Soma
authors.affiliation: Formally of Pfizer Inc., New York, NY.
authors.forename: Jamie
authors.initials: J
authors.lastname: Geier
authors.affiliation: Formally of Pfizer Inc., New York, NY.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kwok
authors.affiliation: Pfizer Inc., Groton, CT.
authors.forename: Richard
authors.initials: R
authors.lastname: Riese
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D017326:Clinical Trials, Phase III as Topic; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000453:epidemiology*; D006973:Hypertension / Q000453:epidemiology; D015994:Incidence; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D014280:Triglycerides; C479163:tofacitinib; D053612:Janus Kinases
keywords: Cardiovascular; Rheumatoid arthritis; Safety; Tofacitinib