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Comparative Effectiveness and Safety of Anti-TNF's in Biologic-Naïve Patients With Crohn's Disease

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Crohn's Disease
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Posted 7/23/2019 4:12 PM (GMT 0)
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.

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

Post Edited (xy123) : 7/23/2019 10:49:26 AM (GMT-6)

Posted 7/23/2019 4:54 PM (GMT 0)
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."
Posted 7/23/2019 6:18 PM (GMT 0)
This is interesting both from a personal perspective (I am biologic-naive and have been "pushed" to try one despite being mild to moderate in dx) & from my work prospective (I work in the health insurance industry and take many things into account when I project care for an individual).
For me...I have been against trying remicade partly due to the "ingredient" source. However, there is a biosimilar that has peaked my interest should I need to go that route. However, this article gives me a sense that none of these are that effective overall. I am still staying in the bottom-up theory for medications for myself.
From my work background - there are some things the study did not take into account (at least what I saw). I have done studies that show patient compliance with medications often is dependent on the delivery system - patients opt for pill over injection over IV. Patients showed lower compliance with medication protocols in self injectables and patient error may come into play. While they also projected their disinterest in IV onto their patient reported outcomes, their compliance with dosing and timing is controlled by provider instead of patient. While weight based is a huge factor in dosage effectiveness, I think that patient outcomes are also impacted by the delivery system here. The study also did not reflect if other medications were used in conjunction with the anti-TNF.
Did the study say who funded it? I have a major curiosity there.
I just spent a day explaining to actuaries that a simple algorithm can not be applied broadly to medical care due to the number of variables (environmental, economic, social, geographic location, personal histories, on and on)---I think this hazed my view of the report. However, I do find it interesting.
Posted 7/23/2019 7:46 PM (GMT 0)

HabsHockeyFan said...

Did the study say who funded it? I have a major curiosity there.

The article said...
Disclosures: This study was made possible by support from (a) the American College of Gastroenterology Clinical Research Award 2014 to SS, and (b) the Center for the Science of Health Care Delivery, Mayo Clinic, and a CTSA Grant UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Dr. Loftus has consulted for and has received research support from Janssen Biotech, AbbVie, and UCB Pharma. Dr. Kappelman has consulted for and has received research support from Janssen Biotech and AbbVie. None of the other authors have any relevant financial disclosures.

Posted 7/24/2019 12:47 PM (GMT 0)
Hmmm. Cynicism reigns in my world here.
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