title: Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials.
abstract: OBJECTIVE
  Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report an integrated safety summary of tofacitinib from two phase I, nine phase II, six phase III and two long-term extension studies in adult patients with active RA.
  
  
  METHODS
  Data were pooled for all tofacitinib-treated patients (data cut-off: 31 March 2015). Incidence rates (IRs; patients with event/100 patient-years) and 95% CIs are reported for adverse events (AEs) of interest.
  
  
  RESULTS
  6194 patients received tofacitinib for a total 19 406 patient-years' exposure; median exposure was 3.4 patient-years. IR (95% CI) for serious AEs was 9.4 (9.0 to 9.9); IR for serious infections was 2.7 (2.5 to 3.0). IR for (all) herpes zoster was 3.9 (3.6 to 4.2); IR for disseminated or multidermatomal herpes zoster was 0.3 (0.2 to 0.4). IR for opportunistic infections (excluding tuberculosis) was 0.3 (0.2 to 0.4) and was 0.2 (0.1 to 0.3) for tuberculosis. IR for malignancies (excluding non-melanoma skin cancer (NMSC)) was 0.9 (0.8 to 1.0); NMSC IR was 0.6 (0.5 to 0.7). IR for gastrointestinal perforations was 0.1 (0.1 to 0.2). Analysis of IR for serious infections, herpes zoster and malignancies by 6-month intervals did not reveal any notable increase in IR with longer-duration tofacitinib exposure.
  
  
  CONCLUSIONS
  This analysis of tofacitinib exposure up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. AEs were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.
  
  
  BACKGROUND
  NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT00413699, NCT00661661; Results.
authors.affiliation: Metroplex Clinical Research Center, Dallas, Texas, USA.
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Cohen
authors.affiliation: University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Paris-Sud University, Le Kremlin Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.affiliation: Seoul National University, Seoul, Republic of Korea.
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.affiliation: University of Queensland, Queensland, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Nash
authors.affiliation: Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Winthrop
authors.affiliation: University of California, Los Angeles, California, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Charles-Schoeman
authors.affiliation: Pfizer Australia, Sydney, Australia.
authors.forename: Krishan
authors.initials: K
authors.lastname: Thirunavukkarasu
authors.affiliation: Pfizer Inc, New York, New York, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: DeMasi
authors.affiliation: Pfizer Inc, New York, New York, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Geier
authors.affiliation: Pfizer Inc, New York, New York, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kwok
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Lisy
authors.initials: L
authors.lastname: Wang
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Riese
authors.affiliation: University of Hamburg, Hamburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wollenhaupt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005260:Female; D006562:Herpes Zoster / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D015994:Incidence; D007239:Infections / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D009894:Opportunistic Infections / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D010880:Piperidines / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects*; D013997:Time Factors; D014376:Tuberculosis / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D055815:Young Adult
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
keywords: Cardiovascular Disease; Infections; Rheumatoid Arthritis; Treatment; Tuberculosis