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

Abstract

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-naïve 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-naïve CD patients (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 hazard analysis, accounting for baseline demographics, healthcare utilization, comorbidities, and use of CD-related medication. Results Compared to 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 to 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 to those of certolizumab pegol-treated patients. All agents had comparable risk of serious infections. Conclusion In a retrospective analysis of a large cohort of biologic-naïve patients with CD, we found infliximab to be superior to adalimumab and certolizumab pegol for patient-relevant outcomes, without increased risk of serious infections.

Comparison of Infliximab and Adalimumab in Biologic-Naive Patients With Ulcerative Colitis: A Nationwide Danish Cohort Study

“…In an administrative claims-based study on 3205 patients with Crohn's disease, we observed that infliximab-treated patients had a lower risk of Crohn's disease-related hospitalization (HR, 0.80; 95% CI, 0.66-0.98), abdominal surgery (HR, 0.76; 95% CI, 0.58-0.99) and corticosteroid use (HR, 0.85; 95% CI, 0.75-0.96). 16 In the U.S. Medicare retrospective cohort study of patients with Crohn's disease, among patients younger than 65 years, Osterman and colleagues also observed that infliximab use was associated with a lower risk of surgery compared to adalimumab (adjusted odds ratio [OR], 0.66; 95% CI, 0.47–0.93). 21 …”

“…16 Based on corticosteroid use, patients were classified as: (a) remote users (if they received prescriptions for corticosteroids in the preceding 90 to 365 prior to index TNF-α inhibitor start date, but not within 90 days prior to start of TNF-α inhibitor), and (b) recent users (if they received prescriptions for corticosteroids in the preceding 90 days prior to index TNF-α inhibitor start date).…”

Improved Long-term Outcomes of Patients With Inflammatory Bowel Disease Receiving Proactive Compared With Reactive Monitoring of Serum Concentrations of Infliximab

“…IBD-related surgery included any intestinal or perianal surgical procedure (eg, bowel resection with or without ostomy or ileal pouch-anal anastomosis, fistulotomy, fistula seton placement, abscess drainage, or strictureplasty). 17 IBD-related hospitalization was defined as any hospitalization with IBD either as the primary diagnosis (ie, for disease relapse, symptomatic fistula or abscess, other complications, or surgery) or secondary diagnosis if the primary diagnosis was related to a gastrointestinal symptom (abdominal pain, diarrhea, nausea, vomiting, constipation, or gastrointestinal bleeding) and not associated with infliximab itself or other comorbidities. 17 SIR was defined as any acute or delayed infusion reaction necessitating infliximab discontinuation.…”

“…17 IBD-related hospitalization was defined as any hospitalization with IBD either as the primary diagnosis (ie, for disease relapse, symptomatic fistula or abscess, other complications, or surgery) or secondary diagnosis if the primary diagnosis was related to a gastrointestinal symptom (abdominal pain, diarrhea, nausea, vomiting, constipation, or gastrointestinal bleeding) and not associated with infliximab itself or other comorbidities. 17 SIR was defined as any acute or delayed infusion reaction necessitating infliximab discontinuation. The study observation time for IBD-related surgery, IBD-related hospitalization, and SIR was defined as the start of TDM until treatment failure (and within 12 weeks of the last infliximab infusion, only if another biologic was not administered) or the end of follow-up.…”

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease

“…23 Few head to head comparisons of different anti-TNFs exist in this situation, although experience suggests that infliximab is preferable for treating active disease. [24][25][26][27][28][29] However, there is less of a consensus on when to introduce biologic agents in patients with Crohn's disease. ECCO guidelines from 2016 still recommend treatment with corticosteroids before starting anti-TNF agents (ECCO statements 5C, 5D, 5E, 5F).…”