title: Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme.
abstract: OBJECTIVE
  Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To further assess the potential role of Janus kinase inhibition in the development of malignancies, we performed an integrated analysis of data from the tofacitinib RA clinical development programme.
  
  
  METHODS
  Malignancy data (up to 10 April 2013) were pooled from six phase II, six Phase III and two long-term extension (LTE) studies involving tofacitinib. In the phase II and III studies, patients with moderate-to-severe RA were randomised to various tofacitinib doses as monotherapy or with background non-biological disease-modifying antirheumatic drugs (DMARDs), mainly methotrexate. The LTE studies (tofacitinib 5 or 10 mg twice daily) enrolled patients from qualifying prior phase I, II and III index studies.
  
  
  RESULTS
  Of 5671 tofacitinib-treated patients, 107 developed malignancies (excluding non-melanoma skin cancer (NMSC)). The most common malignancy was lung cancer (n=24) followed by breast cancer (n=19), lymphoma (n=10) and gastric cancer (n=6). The rate of malignancies by 6-month intervals of tofacitinib exposure indicates rates remained stable over time. Standardised incidence ratios (comparison with Surveillance, Epidemiology and End Results) for all malignancies (excluding NMSC) and selected malignancies (lung, breast, lymphoma, NMSC) were within the expected range of patients with moderate-to-severe RA.
  
  
  CONCLUSIONS
  The overall rates and types of malignancies observed in the tofacitinib clinical programme remained stable over time with increasing tofacitinib exposure.
authors.affiliation: The University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.affiliation: Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Kaplan
authors.affiliation: Pfizer Inc, New York, New York, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kwok
authors.affiliation: Pfizer Inc, New York, New York, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Geier
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Benda
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Koshika
authors.initials: K
authors.lastname: Soma
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
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015994:Incidence; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053616:Janus Kinase 3
keywords: DMARDs (synthetic); Inflammation; Rheumatoid Arthritis; Treatment