title: Analysis of non-melanoma skin cancer across the tofacitinib rheumatoid arthritis clinical programme.
abstract: OBJECTIVE
  Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the incidence of non-melanoma skin cancer (NMSC) across the tofacitinib RA development programme.
  
  
  METHODS
  NMSC events (through August 2013) were identified in patients receiving tofacitinib in two Phase (P)1, eight P2, six P3 and two long-term extension (LTE) studies. In P123 studies, tofacitinib was administered at various doses (1-30 mg twice daily [BID], 20 mg once daily), as monotherapy or with conventional synthetic disease-modifying anti-rheumatic drugs, mainly methotrexate. In LTE studies, patients from qualifying P123 studies received tofacitinib 5 or 10 mg BID. Crude incidence rates (IRs; patients with events/100 patient-years) for first NMSC event were evaluated across doses and over time.
  
  
  RESULTS
  In the overall population, comprising data from 18 studies (15,103 patient-years), 83 of 6092 tofacitinib-treated patients had NMSC events. The IR for NMSC (0.55 [95% confidence interval, 0.45-0.69] overall population) was stable up to 84 months of observation. IRs for tofacitinib 5 and 10 mg BID in combined P123 trials were 0.61 (0.34-1.10) and 0.47 (0.24-0.90), respectively. Corresponding IRs for LTE studies were 0.41 (0.26-0.66) and 0.79 (0.60-1.05).
  
  
  CONCLUSIONS
  The IR for NMSC across the tofacitinib RA clinical development programme was low and remained stable over time. The IR for NMSC in LTE studies was numerically but not significantly higher with tofacitinib 10 versus 5 mg BID; an inverse dose relationship was observed in P123 trials. Longer follow-up is required to confirm these results.
authors.affiliation: The University of Alabama at Birmingham, AL, 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: Dermatology and Laser Center of Maui, Kihei, Hawaii, USA.
authors.forename: George
authors.initials: G
authors.lastname: Martin
authors.affiliation: Université Paris-Sud, and Hôpitaux Universitaires Paris-Sud, Assistance Publique - Hôpitaux de Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Ketti K
authors.initials: KK
authors.lastname: Terry
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Pfizer Inc, New York, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Geier
authors.affiliation: Pfizer Inc, New York, USA.
authors.forename: John
authors.initials: J
authors.lastname: Andrews
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: Mandeep
authors.initials: M
authors.lastname: Kaur
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Fan
authors.affiliation: Pfizer Inc, Collegeville, PA, USA. chudi.i.nduaka@pfizer.com.
authors.forename: Chudy I
authors.initials: CI
authors.lastname: Nduaka
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002280:Basal Cell Carcinoma / Q000453:epidemiology*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; 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; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology*
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D008727:Methotrexate