title: Intravenous Versus Subcutaneous Anti-TNF-Alpha Agents for Crohn's Disease: A Comparison of Effectiveness and Safety.
abstract: BACKGROUND
  In recent years, there have been a number of pharmacological innovations for Crohn's disease (CD), a difficult-to-treat condition, including new treatment philosophies (e.g., top-down therapy) and new therapeutic options in terms of the agent and the route of administration. Three anti-tumor necrosis factor (anti-TNF-alpha) agents are available for use among CD patients in the United States: infliximab, an intravenous agent, and adalimumab and certolizumab pegol, 2 newer subcutaneous products. Infliximab is considered the "gold standard" because it has the longest clinical experience, and adalimumab and certolizumab pegol have each gained significant market share.
  
  
  OBJECTIVE
  To examine differences in effectiveness and safety between currently available intravenous and subcutaneous anti-TNF-alpha agents used to treat patients with CD.
  
  
  METHODS
  Data for this retrospective, administrative claims analysis were obtained from pharmacy and medical claims from major U.S. health plans geographically dispersed across 14 states during 2007-2011. Patients had at least 1 ICD-9-CM diagnosis for CD, 6 months pre-index eligibility, and initiated anti-TNF-alpha therapy on the index date. Patients in each cohort were propensity score matched on pre-index demographics, clinical characteristics, and baseline health care use. During the post-index period, age-sex adjusted incidence rate ratios (IRRs) of CD-related symptoms, infections, cancers, and hepatic-related conditions were compared using Cox (PH) models.
  
  
  RESULTS
  The matched cohorts included 515 patients in each group, with an average age of 39 years. Median follow-up was 17.5 months in the intravenous cohort and 17.7 months in the subcutaneous cohort. In terms of effectiveness outcomes, age-sex adjusted IRRs for the subcutaneous group, with the intravenous cohort as a reference, were as follows: 0.61 (95% CI = 0.32-1.18, P = 0.14) for anal fissures; 0.97 (95% CI = 0.72-1.30, P = 0.85) for abscess; 1.08 (95% CI = 0.79-1.04, P = 0.64) for fistulas; 1.12 (95% CI = 0.83-1.54, P = 0.45) for gastrointestinal hemorrhage; and 1.22 (95% CI = 0.93-1.59, P = 0.14) for a combined measure of obstruction, occlusion, stenosis, and stricture of intestine. In terms of safety outcomes, age-sex adjusted IRRs for the subcutaneous group were as follows: 0.85 (95% CI = 0.62-1.16, P = 0.30) for infections; 1.16 (95% CI = 0.71-1.89, P = 0.55) for cancers; and 1.23 (95% CI = 0.79-1.92, P = 0.35) for hepatic-related conditions.
  
  
  CONCLUSIONS
  After adjusting for baseline characteristics, effectiveness and safety outcomes appear to be comparable between intravenous and subcutaneous anti-TNF-alpha agents in patients with CD. With similar outcomes, other considerations such as convenience of administration and patient preference may play a more prominent role in choice of agent. Health care providers and health payers should inform CD patients about the range of options available when selecting an anti-TNF-alpha agent.
authors.affiliation: HealthCore, Inc., 123 Justison Ave., Ste. 200, Wilmington, DE 19801. adevries@healthcore.com.
authors.forename: Jinan
authors.initials: J
authors.lastname: Liu
authors.forename: Gosia
authors.initials: G
authors.lastname: Sylwestrzak
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Ruggieri
authors.forename: Andrea
authors.initials: A
authors.lastname: DeVries
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D061605:Administration, Intravenous; D000328:Adult; D000068582:Certolizumab Pegol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068582:Certolizumab Pegol