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 hepaticrelated 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.