title: Comparative Effectiveness and Safety of Anti-Tumor Necrosis Factor Agents in Biologic-Naive Patients With Crohn's Disease.
abstract: Inhibitors of tumor necrosis factor (anti-TNF agents) are the most effective therapy for Crohn's disease (CD). We evaluated the real-world comparative effectiveness and safety of different anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) in biologic-naive patients with CD in a retrospective, propensity-matched cohort study using a national administrative claims database (Optum Labs Data Warehouse).
  
  
  
  We identified 3205 biologic-naive patients with CD (mean age, 41 ± 15 years; 45% male; median follow-up period after anti-TNF therapy, 19 months; 44.5% on infliximab and 38.9% on adalimumab) who received their first prescription for an anti-TNF agent (infliximab, adalimumab, or certolizumab pegol) after a 12-month period without any anti-TNF treatment (baseline), and with a minimum follow-up period of 6 months after their initial anti-TNF prescription, between 2006 and 2014. The primary outcomes were all-cause and CD-related hospitalization, abdominal surgery, corticosteroid use, and serious infections. We performed a propensity-matched, Cox proportional hazards analysis, accounting for baseline demographics, health care use, comorbidities, and use of CD-related medication.
  
  
  
  Compared with adalimumab-treated patients, infliximab-treated patients had a lower risk of CD-related hospitalization (adjusted hazard ratio [aHR], 0.80; 95% confidence interval [CI], 0.66-0.98), abdominal surgery (aHR, 0.76; 95% CI, 0.58-0.99), and corticosteroid use (aHR, 0.85; 95% CI, 0.75-0.96). Compared with certolizumab pegol-treated patients, infliximab-treated patients had a lower risk of all-cause hospitalization (aHR, 0.70; 95% CI, 0.52-0.95) and CD-related hospitalization (aHR, 0.59; 95% CI, 0.39-0.90). Adalimumab-treated patients had outcomes comparable with those of certolizumab pegol-treated patients. All agents had comparable risk of serious infections.
  
  
  
  In a retrospective analysis of a large cohort of biologic-naive patients with CD, we found infliximab to be superior to adalimumab and certolizumab pegol for patient-relevant outcomes, without increased risk of serious infections.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Division of Gastroenterology, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, University of California San Diego, La Jolla, California. Electronic address: sis040@ucsd.edu.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Singh
authors.affiliation: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Heien
authors.affiliation: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Sangaralingham
authors.affiliation: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Schilz
authors.affiliation: Division of Pediatric Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kappelman
authors.affiliation: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota; Division of Health Care Policy and Research, Department of Health Services Research, Mayo Clinic, Rochester, Minnesota; Optum Labs, Cambridge, Massachusetts.
authors.forename: Nilay D
authors.initials: ND
authors.lastname: Shah
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Loftus
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D001688:Biological Products / Q000008:administration & dosage* / Q000009:adverse effects*; D000068582:Certolizumab Pegol / Q000008:administration & dosage / Q000009:adverse effects; D003424:Crohn Disease / Q000628:therapy*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects*; D000069285:Infliximab / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D001688:Biological Products; D007155:Immunologic Factors; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068582:Certolizumab Pegol
keywords: Biologics; Database Analysis; Propensity Matching; Real-World Effectiveness