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Clin Gastroenterol Hepatol. Author manuscript; available in PMC 2017 Aug 1.
Published in final edited form as:
Clin Gastroenterol Hepatol. 2016 Aug; 14(8): 1120–1129.e6.
Published online 2016 Apr 4. doi: 10.1016/j.cgh.2016.03.038
PMCID: PMC4955682
NIHMSID: NIHMS776209
PMID: 27058635
Comparative Effectiveness and Safety of Anti-Tumor Necrosis Factor Agents in Biologic-Naïve Patients with Crohn’s Disease
Siddharth Singh, M.D., M.S.,1,2,3 Herbert C. Heien, M.S.,4 Lindsey R. Sangaralingham, M.P.H.,4 Stephanie R. Schilz, B.A.,4 Michael D. Kappelman, M.D., M.P.H.,5 Nilay D. Shah, Ph.D.,4,6,7 and Edward V. Loftus, Jr., M.D.1
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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955682/
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, propensity 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 prescription. 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."
Published in final edited form as:
Clin Gastroenterol Hepatol. 2016 Aug; 14(8): 1120–1129.e6.
Published online 2016 Apr 4. doi: 10.1016/j.cgh.2016.03.038
PMCID: PMC4955682
NIHMSID: NIHMS776209
PMID: 27058635
Comparative Effectiveness and Safety of Anti-Tumor Necrosis Factor Agents in Biologic-Naïve Patients with Crohn’s Disease
Siddharth Singh, M.D., M.S.,1,2,3 Herbert C. Heien, M.S.,4 Lindsey R. Sangaralingham, M.P.H.,4 Stephanie R. Schilz, B.A.,4 Michael D. Kappelman, M.D., M.P.H.,5 Nilay D. Shah, Ph.D.,4,6,7 and Edward V. Loftus, Jr., M.D.1
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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955682/
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, propensity 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 prescription. 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."
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