title: Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies.
abstract: OBJECTIVE
  To describe the longterm safety and efficacy profile of tofacitinib in patients with moderate to severe active rheumatoid arthritis (RA).
  
  
  METHODS
  Data were pooled from 2 open-label studies (NCT00413699, NCT00661661) involving patients who had participated in qualifying phase I, II, or III index studies of tofacitinib. Safety data included over 60 months of observation; efficacy data are reported up to Month 48. Treatment was initiated with tofacitinib 5 or 10 mg twice daily. Primary endpoints were adverse events (AE) and laboratory safety data. Secondary endpoints included American College of Rheumatology (ACR) response rates, and Disease Activity Score (28 joints) (DAS28)-4[erythrocyte sedimentation rate (ESR)] and Health Assessment Questionnaire-Disability Index (HAQ-DI) assessments.
  
  
  RESULTS
  Overall, 4102 patients were treated for 5963 patient-years; mean (maximum) treatment duration was 531 (1844) days; 20.8% of patients discontinued treatment over 60 months. The most common AE were nasopharyngitis (12.7%) and upper respiratory tract infection (10.5%). Serious AE were reported in 15.4% of patients with an exposure-estimated incidence rate of 11.1 events/100 patient-years. Serious infections were reported in 4.5% of patients with an exposure-estimated incidence rate of 3.1 events/100 patient-years (95% CI: 2.66-3.55). Mean values for laboratory variables were stable over time and consistent with phase II and III studies. Persistent efficacy was demonstrated through Month 48, as measured by ACR response rate (ACR20/50/70) DAS28-4-ESR, and HAQ-DI. Safety and efficacy were similar for patients receiving tofacitinib as monotherapy or with background nonbiologic disease-modifying antirheumatic drugs.
  
  
  CONCLUSIONS
  Tofacitinib demonstrated consistent safety and persistent efficacy over 48 months in patients with RA.
authors.affiliation: From the Schoen Klinik Hamburg, Hamburg, Germany; Healthpoint Medical Group, Tampa, Florida, USA; Seoul National University, Seoul, Republic of Korea; The University of Alabama at Birmingham, Birmingham, Alabama; Pfizer Inc., Groton, Connecticut; Pfizer Inc., Collegeville, Pennsylvania, USA; Pfizer Japan Inc., Tokyo, Japan.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wollenhaupt
authors.forename: Joel
authors.initials: J
authors.lastname: Silverfield
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.forename: Susan P
authors.initials: SP
authors.lastname: Wood
authors.forename: Koshika
authors.initials: K
authors.lastname: Soma
authors.forename: Chudy I
authors.initials: CI
authors.lastname: Nduaka
authors.forename: Birgitta
authors.initials: B
authors.lastname: Benda
authors.forename: David
authors.initials: D
authors.lastname: Gruben
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komuro
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Zwillich
authors.forename: Lisy
authors.initials: L
authors.lastname: Wang
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Riese
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects*; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053616:Janus Kinase 3
keywords: ANTIRHEUMATIC AGENTS; CLINICAL TRIAL; RHEUMATOID ARTHRITIS; TOFACITINIB