Durability of Infliximab Dose Intensification in Crohn's Disease
ABSTRACT Dose intensification is a common approach to treat Crohn's disease (CD) patients who lose response to infliximab maintenance therapy. Few studies have reported upon its long-term efficacy or predictors of response.
The goal of this study is to investigate durability and predictors of response to dose intensification-including method of dose intensification, combination immunomodulator therapy, and premedication with intravenous hydrocortisone.
We performed a retrospective study of dose-intensified CD patients at our institution. Dose intensification was defined as an increase in dose from 5 to 10 mg/kg, an increase in frequency of infusions from every 8 weeks to every 6 weeks or less, or both an increase in dose and frequency.
Thirty CD patients (mean age, 39.9 years) met study criteria and underwent dose intensification. Ten (33.3%) patients remained on dose intensification at the end of our study or returned to their former infliximab dose or schedule (median follow-up, 41 months). Fourteen patients (46.7%) eventually lost response to dose intensification, but dose intensification extended infliximab therapy by a median duration of 9 months. Six patients (20%) didn't respond to dose intensification. Neither method of dose intensification, combination immunomodulator therapy, nor premedication with intravenous hydrocortisone predicted initial or durable response to dose intensification. However, analysis of predictors was limited by the small sample size of our study.
The majority of CD patients respond to dose intensification, and a substantial portion will experience durable response such that infliximab therapy is successfully extended by one or more years.
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ABSTRACT: Background: Infliximab, a monoclonal antibody tumor necrosis factor-alpha inhibitor, is an effective therapy that is indicated for the treatment of patients with Crohn’s disease. Although dose escalation from 5 mg/kg to 10 mg/kg is allowed according to the prescribing label of infliximab, conflicting results exist regarding the rate at which this escalation may occur, which may affect payers and providers. Objective: The goal of this exploratory study was to characterize and quantify the rate of infliximab dose escalation in a sample of patients with Crohn’s disease. Methods: Administrative claims data from patients with Crohn’s disease in a large mid-Atlantic managed care organization were collected and used to target and recruit providers into a chart review study of infliximab dosing. Data from the charts of 161 patients with Crohn’s disease who were receiving infliximab between 2006 and 2010 were extracted. Patients were grouped into an infliximab dose-escalation group or a dose-stable group based on these data. The evidence of any infliximab dose ≥7.5 mg/kg or evidence of a mean maintenance interval of 42 days or less resulted in the placement of a patient in the dose-escalation group, with the balance of patients comprising the stable-dose group. Results: A total of 925 infliximab infusions were captured from 161 patients. Of the 161 patients identified, 110 had at least 4 infusions, and 4 had missing data; therefore, only 106 (66%) patients were qualified for the final infliximab dosing analysis. A total of 18 (17%) of these patients had evidence of infliximab dose escalation (dose-escalation group), and the remaining 88 (83%) patients had a consistent 5-mg/kg dose and schedule (stable-dose group). Of the 18 patients in the dose-escalation group, 9 (50%) had a decrease in maintenance interval, whereas 12 (66.7%) patients had an increase in their dosage. A total of 3 (16.7%) patients had both an increase in dose and a reduction in maintenance interval. Conclusions: Infliximab has been shown to be a cost-effective treatment for patients with Crohn’s disease. The rate of infliximab dose escalation in this study was within the lower range of published estimates for this medication. Studies using larger sample sizes are needed to validate the findings of the current study. In addition, studies that are focused on quantifying and describing the nature of infliximab dose escalation may be useful in the development of successful patient–treatment matching algorithms.American Health and Drug Benefits 04/2014; 7(2):87-93.
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ABSTRACT: Background: Certolizumab pegol (CERT) is indicated for reducing the signs and symptoms of Crohn's disease (CD) and maintaining clinical response. Patients losing response received an extra "capture" re-induction dose in the PRECiSE 4 study. We examined the use of certolizumab in a retrospective cohort of patients with CD at a single inflammatory bowel disease center. Methods: We conducted a retrospective chart review of all adult patients with CD treated with CERT at the University of Chicago from April 22, 2008 to May 1, 2011. Demographics, disease characteristics, inflammatory bowel disease therapies, surgeries, CERT dosing, and clinical outcomes were recorded. Predictors of clinical response, re-induction dosing, and maintenance dose escalation were evaluated. Univariate, multivariate, and Kaplan-Meier analyses were performed for predictive variables of clinical response, re-induction dosing, and maintenance dose increases. Results: One hundred ten patients were identified; 23 were excluded. The remaining 87 patients had a sustained clinical response of 31.0%, remission of 14.9%, minimal or no response of 31.0%; 37.9% initially responded but lost response. In total, 35.6% of patients received a single re-induction dose of 400 mg after a mean of 29 weeks, predicted by prior anti-tumor necrosis factor (P = 0.007) and absence of perianal disease (P = 0.006); only 5 patients (16.1%) maintained a durable response or remission; 11.5% increased maintenance dosage after a mean of 50 weeks; all but 1 subsequently stopped CERT. Conclusions: Some patients with CD (31%) achieved a sustained response. The majority of patients receiving re-induction dosing did not achieve a sustained clinical response. Previous treatment with anti-tumor necrosis factor therapy was associated with reduced responses, suggesting that CERT may be more effective as an initial anti-tumor necrosis factor therapy.Inflammatory Bowel Diseases 08/2014; 20(10). DOI:10.1097/MIB.0000000000000146 · 5.12 Impact Factor
- Gut 06/2014; 63(12). DOI:10.1136/gutjnl-2014-307126 · 13.32 Impact Factor