title: Cumulative incidence of, risk factors for, and outcome of dermatological complications of anti-TNF therapy in inflammatory bowel disease: a 14-year experience.
abstract: OBJECTIVE
  The broader and prolonged use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) could expose patients to an increased risk of adverse reactions, including dermatological complications. We assessed the cumulative incidence of anti-TNF-induced cutaneous adverse reactions in IBD patients, their risk factors, their dermatological management, and their outcome in a large cohort of IBD patients.
  
  
  METHODS
  In a single-center observational retrospective study, including all consecutive adult IBD patients treated with an anti-TNF agent between 2001 and 2014, all patients with dermatological complications under anti-TNF therapy were identified in a well-defined cohort of IBD patients. We conducted a survival analysis to determine the cumulative incidence of dermatological complications and risk factors for developing any dermatological complications, cutaneous infections, and psoriasiform lesions. Survival curves were estimated by the Kaplan-Meier method, and we used a Cox proportional hazards model to test the association between parameters and time to each event: any dermatological complication, cutaneous infections, and psoriasis lesions.
  
  
  RESULTS
  Among 583 IBD patients, 176 dermatological complications occurred, involving 20.5% of patients. Median duration of follow-up was 38.2 months (range: 1-179). Psoriasiform lesions (10.1%; 59/583) and cutaneous infections (11.6%, 68/583) were the most frequently observed, with a cumulative incidence of, respectively, 28.9% and 17.6% at 10 years. They led to anti-TNF discontinuation, respectively, in 18.6% and 2.9% of patients. In case of switching to another anti-TNF agent for psoriasiform lesions, recurrence occurred in 57% of patients. Ulcerative colitis was associated with a lower risk of developing cutaneous infections than Crohn's disease (hazard ratio (HR)=0.25; 95% confidence interval (CI)=0.09-0.68; P=0.007). Higher dosing of anti-TNF agent was associated with a higher risk of developing cutaneous infections (HR=1.99; 95% CI=1.09-3.64; P=0.025). A younger age at time of anti-TNF initiation was associated with a higher risk of dermatological complications (HR=2.25; 95% CI=1.39-3.62; P<0.001).
  
  
  CONCLUSIONS
  Dermatological complications involve one of five patients treated with anti-TNF therapy after a 14-year follow-up. Association of cutaneous infections with higher anti-TNF dosing suggests a dose-dependent effect. Discontinuation of anti-TNF therapy due to dermatological complications is required in one out of five patients with psoriasiform lesions, but specific dermatological treatment allows to continue anti-TNF therapy in half of them.
authors.affiliation: Department of Dermatology and Allergy, University Hospital of Nancy, Lorraine University, Vandoeuvre-Les-Nancy, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Fréling
authors.affiliation: ESPRI-BIOBASE Unit, PARC, University Hospital of Nancy, Vandoeuvre-Les-Nancy, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Baumann
authors.affiliation: Department of Dermatology and Allergy, University Hospital of Nancy, Lorraine University, Vandoeuvre-Les-Nancy, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cuny
authors.affiliation: Inserm U954, Department of Hepato-Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-Les-Nancy, France.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Bigard
authors.affiliation: Department of Dermatology and Allergy, University Hospital of Nancy, Lorraine University, Vandoeuvre-Les-Nancy, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Schmutz
authors.affiliation: Department of Dermatology and Allergy, University Hospital of Nancy, Lorraine University, Vandoeuvre-Les-Nancy, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Barbaud
authors.affiliation: Inserm U954, Department of Hepato-Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-Les-Nancy, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D015994:Incidence; D000069285:Infliximab; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016016:Proportional Hazards Models; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy / Q000453:epidemiology*; D012189:Retrospective Studies; D012307:Risk Factors; D012874:Skin Diseases, Infectious / Q000139:chemically induced / Q000188:drug therapy / Q000453:epidemiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab