Comparative Effectiveness and Safety of Anti-Tumor Necrosis Factor Agents in Biologic-Naive Patients With Crohn's Disease

Clin Gastroenterol Hepatol. 2016 Aug;14(8):1120-1129.e6. doi: 10.1016/j.cgh.2016.03.038. Epub 2016 Apr 4.


Background & aims: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Biologics; Database Analysis; Propensity Matching; Real-World Effectiveness.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adalimumab / administration & dosage
  • Adalimumab / adverse effects
  • Adult
  • Biological Products / administration & dosage*
  • Biological Products / adverse effects*
  • Certolizumab Pegol / administration & dosage
  • Certolizumab Pegol / adverse effects
  • Crohn Disease / therapy*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / adverse effects*
  • Infliximab / administration & dosage
  • Infliximab / adverse effects
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Biological Products
  • Immunologic Factors
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Certolizumab Pegol