title: Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis: 5-year follow-up of a Danish nationwide cohort.
abstract: BACKGROUND
  Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients with severe psoriasis treated with systemic anti-inflammatory drugs.
  
  
  METHODS
  Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular events associated with use of biological drugs, methotrexate, cyclosporine, retinoids and other antipsoriatic therapies, including topical treatments, phototherapy and climate therapy.
  
  
  RESULTS
  A total of 6902 patients (9662 treatment exposures) with a maximum follow-up of 5 years were included. Incidence rates per 1000 patients-years for cardiovascular events were 4.16, 6.28, 6.08, 18.95 and 14.63 for biological drugs, methotrexate, cyclosporine, retinoid and other therapies respectively. Relative to other therapies, methotrexate (HR 0.53; CI 0.34-0.83) was associated with reduced risk of the composite endpoint and a comparable but non-significant protective effect was observed with biological drugs (HR 0.58; CI 0.30-1.10), whereas no protective effect was apparent with cyclosporine (HR 1.06; CI 0.26-4.27) and retinoids (HR 1.80; CI 1.03-2.96). Tumour necrosis factor inhibitors (HR 0.46; CI 0.22-0.98) were linked to reduced event rates, whereas the interleukin-12/23 inhibitor ustekinumab (HR 1.52; CI 0.47-4.94) was not.
  
  
  CONCLUSIONS
  Systemic anti-inflammatory treatment with methotrexate was associated with significantly lower rates of cardiovascular events during long-term follow-up compared to patients treated with other antipsoriatic therapies. The treatment strategy in patients with severe psoriasis may have an impact on cardiovascular outcomes and randomized trials to evaluate the cardiovascular safety and efficacy of systemic antipsoriatic therapies are called for.
authors.affiliation: Department of Cardiology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Ahlehoff
authors.affiliation: Department of Dermatology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Skov
authors.affiliation: Department of Cardiology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|The Danish National Institute of Public Health, University of Southern, Copenhagen, Denmark.
authors.forename: G
authors.initials: G
authors.lastname: Gislason
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: R
authors.initials: R
authors.lastname: Gniadecki
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Iversen
authors.affiliation: Department of Dermatology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark.
authors.forename: L E
authors.initials: LE
authors.lastname: Bryld
authors.affiliation: Department of Dermatology, Odense University Hospital, Odense, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Lasthein
authors.affiliation: Department of Rheumatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Lindhardsen
authors.affiliation: Department of Cardiology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: S L
authors.initials: SL
authors.lastname: Kristensen
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Torp-Pedersen
authors.affiliation: Department of Cardiology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: P R
authors.initials: PR
authors.lastname: Hansen
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001688:Biological Products / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000401:mortality*; D002423:Cause of Death; D013790:Climatotherapy; D016572:Cyclosporine / Q000627:therapeutic use; D003718:Denmark / Q000453:epidemiology; D003879:Dermatologic Agents / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D010789:Phototherapy; D011565:Psoriasis / Q000188:drug therapy* / Q000628:therapy; D012042:Registries; D012176:Retinoids / Q000627:therapeutic use; D012720:Severity of Illness Index; D020521:Stroke / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000069549:Ustekinumab / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D003879:Dermatologic Agents; D012176:Retinoids; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D000069549:Ustekinumab; D008727:Methotrexate