title: Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden.
abstract: OBJECTIVE
  To investigate the risk of squamous cell and basal cell skin cancer in patients with rheumatoid arthritis naive to biologic drugs, in patients starting tumour necrosis factor (TNF) inhibitor treatment, and in the general population.
  
  
  METHODS
  Population based cohort study.
  
  
  METHODS
  Nationwide data from Sweden.
  
  
  METHODS
  Cohort of patients with rheumatoid arthritis naive to biologics (n=46 409), cohort of patients with rheumatoid arthritis starting TNF inhibitor treatment as first biologic in 1998-2012 (n=12 558), and matched general population comparator cohort, identified through national quality of care and health registers.
  
  
  METHODS
  Hazard ratio of first in situ or invasive squamous cell skin cancer (1998-2012) and first basal cell cancer (2004-12).
  
  
  RESULTS
  For basal cell cancer, the hazard ratio was 1.22 (95% confidence interval 1.07 to 1.41) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.14 (0.98 to 1.33; 236 v 1587 events) comparing TNF inhibitor treated patients with biologics-naive patients. For squamous cell cancer, the hazard ratio was 1.88 (1.74 to 2.03) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.30 (1.10 to 1.55; 191 v 847 events) comparing TNF inhibitors with biologics-naive patients; the latter translated to an annual number needed to harm in the order of 1600. Among people with a history of squamous cell or basal cell cancer, TNF inhibitors did not further increase risks.
  
  
  CONCLUSIONS
  A small to moderately increased risk of basal cell cancer was seen in biologics-naive rheumatoid arthritis patients, with no further effect of TNF inhibitors. For squamous cell cancer, the risk was nearly doubled in biologics-naive patients, with a further 30% increase in risk among patients treated with TNF inhibitors; this translates to one additional case for every 1600 years of treatment experience, assuming that this association reflected causality. Vigilance regarding skin malignancies may be advisable in rheumatoid arthritis, irrespective of TNF inhibitor treatment. Most of the increase in risk for non-melanoma skin cancer in patients with rheumatoid arthritis treated with TNF inhibitors originates from factors other than that treatment.
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, 171 76 Stockholm, Sweden Pauline.raaschou@karolinska.se.
authors.forename: Pauline
authors.initials: P
authors.lastname: Raaschou
authors.affiliation: Department of Health Research and Policy and Division of Immunology and Rheumatology, Department of Medicine, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Julia F
authors.initials: JF
authors.lastname: Simard
authors.affiliation: Clinical Pharmacology Unit, Department of Medicine Solna, Karolinska Institutet.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Asker Hagelberg
authors.affiliation: Clinical Epidemiology Unit and Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet.
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology; D002280:Basal Cell Carcinoma / Q000139:chemically induced* / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D013548:Sweden / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha
references.citation: J Rheumatol. 2005 Nov;32(11):2130-5
references.pmid: 16265690
references.citation: Ann Rheum Dis. 2006 Jun;65(6):707-12
references.pmid: 16414975
references.citation: Arthritis Rheum. 2007 Sep;56(9):2886-95
references.pmid: 17729297
references.citation: Acta Oncol. 2009;48(1):27-33
references.pmid: 18767000
references.citation: Nat Rev Cancer. 2009 May;9(5):361-71
references.pmid: 19343034
references.citation: Ann Rheum Dis. 2009 Jul;68(7):1136-45
references.pmid: 18753157
references.citation: Int J Cancer. 2009 Oct 15;125(8):1747-54
references.pmid: 19444916
references.citation: Arthritis Rheum. 2011 Jan;63(1):26-36
references.pmid: 20862678
references.citation: Pharmacoepidemiol Drug Saf. 2011 Feb;20(2):119-30
references.pmid: 21254282
references.citation: Ann Rheum Dis. 2011 Mar;70(3):516-9
references.pmid: 21081525
references.citation: Rheumatology (Oxford). 2011 Aug;50(8):1431-9
references.pmid: 21415022
references.citation: J Am Acad Dermatol. 2011 Aug;65(2):253-61; quiz 262
references.pmid: 21763561
references.citation: J Dermatolog Treat. 2011 Aug;22(4):229-32
references.pmid: 20666674
references.citation: Ann Rheum Dis. 2011 Nov;70(11):1895-904
references.pmid: 21885875
references.citation: Ann Rheum Dis. 2012 Jun;71(6):869-74
references.pmid: 22241900
references.citation: Arch Dermatol. 2012 Aug;148(8):939-46
references.pmid: 22711192
references.citation: Ann Rheum Dis. 2013 Jan;72(1):79-82
references.pmid: 22945500
references.citation: Rheumatology (Oxford). 2013 Jan;52(1):91-8
references.pmid: 23238979
references.citation: Arthritis Rheum. 2013 Jan;65(1):48-58
references.pmid: 23055441
references.citation: J Am Acad Dermatol. 2014 Aug;71(2):359-65
references.pmid: 24725477
references.citation: Br J Dermatol. 2000 Sep;143(3):513-9
references.pmid: 10971322
references.citation: J Am Acad Dermatol. 2001 Dec;45(6):953-6
references.pmid: 11712048
references.citation: J Epidemiol Community Health. 2002 Aug;56(8):606-10
references.pmid: 12118052
references.citation: Br J Cancer. 2003 Oct 6;89(7):1221-7
references.pmid: 14520450
references.citation: Transplantation. 1990 Mar;49(3):506-9
references.pmid: 2316011
references.citation: J Natl Cancer Inst. 1993 Feb 17;85(4):307-11
references.pmid: 8426374
references.citation: Eur J Cancer. 1996 Sep;32A(10):1753-7
references.pmid: 8983286
references.citation: Ann Rheum Dis. 2005 Oct;64(10):1421-6
references.pmid: 15829572