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, pr
opensity-matched cohort study using a national administrative claims database (Optum Labs Data Warehouse).
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 prescript
ion 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 prescript
ion, between 2006 and 2014. The primary outcomes were all-cause and CD-related hospitalization, abdominal surgery, corticosteroid use, and serious infections. We performed a pr
opensity-matched, Cox proportional hazard analysis, accounting for baseline demographics, healthcare utilization, comorbidities, and use of CD-related medication.
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.
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.Singh, Siddharth et al. “Comparative Effectiveness and Safety of Anti-Tumor Necrosis Factor Agents in Biologic-Naive Patients With Crohn's Disease.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association vol. 14,8 (2016): 1120-1129.e6. doi:10.1016/j.cgh.2016.03.038
From the article:
"While anti-TNF-based therapy is the most effective treatment for CD, there are limited data on the comparative effectiveness and safety of different anti-TNF agents. In this nationally representative, pr
opensity score-matched retrospective cohort study of 3,205 biologic-naïve patients with CD, we made several key observations. First, we observed that IFX-treated patients had lower risks of CD-related hospitalization, abdominal surgery and corticosteroid use compared to patients treated with ADA or CZP as the index anti-TNF agent. Second, patients started on IFX or ADA as the index anti-TNF agent were more likely to stay on their index agent at 6- and 12-months as compared to CZP-treated patients, even after adjusting for calendar year of prescript
ion. Third, there was no significant difference in the risk of serious infections requiring hospitalization in IFX-, ADA- or CZP-treated patients. Based on the findings of our observational study, IFX may be superior to other anti-TNF agents for the treatment of CD. This is one of the largest observational comparative effectiveness studies in a contemporary cohort of biologic-naïve Crohn’s disease patients, with patient-centered effectiveness and safety outcomes, assessed with robust complementary statistical approaches, with several stratified and/or sensitivity analyses."
"Despite all three anti-TNF agents having a similar mechanism of action, there are subtle differences in pharmacokinetics, which may explain these results. IFX, administered intravenously, is dosed based on body weight, whereas ADA- and CZP- have a fixed dose administered subcutaneously. In a retrospective cohort study, Bhalme et al observed differences in the rates of dose escalation due to therapeutic failure based on body mass index (BMI) in ADA-treated, but not IFX-treated, patients with CD.15 In an exploratory analysis of trials of ADA in patients with psoriasis, the response rate decreased progressively with increasing quartile of weight, from 74–79% in the lowest quartile to 62–71% in the highest quartile.16 In contrast, in a pooled analysis of 3 randomized controlled trials of IFX in psoriasis, the response rates were comparable in normal weight, overweight and obese patients (78% vs. 78% vs. 74%, p=not significant). CZP, in contrast to both ADA and IFX, has a slightly different mechanism of action, and does not have complement-mediated or antibody-mediated cell-dependent cytotoxicity due to absence of IgG1-Fc portion.8 Hence, the clinical response to CZP may be different from ADA and IFX."