Dataset Information

Proactive Vs Reactive Therapeutic Drug Monitoring of Infliximab in Crohn's Disease: A Cost-Effectiveness Analysis in a Simulated Cohort.

ABSTRACT:

Background

Therapeutic drug monitoring (TDM) is increasingly performed for Infliximab (IFX) in patients with Crohn's disease (CD). Reactive TDM is a cost-effective strategy to empiric IFX dose escalation. The cost-effectiveness of proactive TDM is unknown. The aim of this study is to assess the cost-effectiveness of proactive vs reactive TDM in a simulated population of CD patients on IFX.

Methods

We developed a stochastic simulation model of CD patients on IFX and evaluated the expected health costs and outcomes of a proactive TDM strategy compared with a reactive strategy. The proactive strategy measured IFX concentration and antibody status every 6 months, or at the time of a flare, and dosed IFX to a therapeutic window. The reactive strategy only did so at the time of a flare.

Results

The proactive strategy led to fewer flares than the reactive strategy. More patients stayed on IFX in the proactive vs reactive strategy (63.4% vs 58.8% at year 5). From a health sector perspective, a proactive strategy was marginally cost-effective compared with a reactive strategy (incremental cost-effectiveness ratio of $146,494 per quality-adjusted life year), assuming a 40% of the wholesale price of IFX. The results were most sensitive to risk of flaring with a low IFX concentration and the cost of IFX.

Conclusions

Assuming 40% of the average wholesale acquisition cost of biologic therapies, proactive TDM for IFX is marginally cost-effective compared with a reactive TDM strategy. As the cost of infliximab decreases, a proactive monitoring strategy is more cost-effective.

SUBMITTER: Negoescu DM

PROVIDER: S-EPMC6905301 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proactive Vs Reactive Therapeutic Drug Monitoring of Infliximab in Crohn's Disease: A Cost-Effectiveness Analysis in a Simulated Cohort.

Negoescu Diana M DM Enns Eva A EA Swanhorst Brooke B Baumgartner Bonnie B Campbell James P JP Osterman Mark T MT Papamichael Konstantinos K Cheifetz Adam S AS Vaughn Byron P BP

Inflammatory bowel diseases 20200101 1

<h4>Background</h4>Therapeutic drug monitoring (TDM) is increasingly performed for Infliximab (IFX) in patients with Crohn's disease (CD). Reactive TDM is a cost-effective strategy to empiric IFX dose escalation. The cost-effectiveness of proactive TDM is unknown. The aim of this study is to assess the cost-effectiveness of proactive vs reactive TDM in a simulated population of CD patients on IFX.<h4>Methods</h4>We developed a stochastic simulation model of CD patients on IFX and evaluated the e ...[more]

PMID: 31184366

Similar Datasets

Project description:IntroductionPerianal fistulising Crohn's disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy.Methods and analysisPatients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18-80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate.Ethics and disseminationResults will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.

Project description:BACKGROUND & AIMS:Monitoring serum concentrations of tumor necrosis factor antagonists in patients receiving these drugs as treatment for inflammatory bowel disease (IBD), also called therapeutic drug monitoring, is performed either after patient loss of response (reactive drug monitoring) or in patients in clinical remission in which the drug is titrated to a target concentration (proactive drug monitoring). We compared long-term outcomes of patients with IBD undergoing proactive vs reactive monitoring of serum concentrations of infliximab. METHODS:We performed a multicenter, retrospective study of 264 consecutive patients with IBD (167 with Crohn's disease) receiving infliximab maintenance therapy. The subjects received proactive (n = 130) or reactive (n = 134) drug monitoring, based on measurements of first infliximab concentration and antibodies to infliximab, from September 2006 to January 2015; they were followed through December 2015 (median time of 2.4 years). We analyzed time to treatment failure, first IBD-related surgery or hospitalization, serious infusion reaction, and detection of antibodies to infliximab. Treatment failure was defined as drug discontinuation for loss of response or serious adverse event, or need for surgery. RESULTS:Multiple Cox regression analysis independently associated proactive drug monitoring, compared with reactive monitoring, with reduced risk for treatment failure (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.09-0.27; P < .001), IBD-related surgery (HR, 0.30; 95% CI, 0.11-0.80; P = .017), IBD-related hospitalization (HR, 0.16; 95% CI, 0.07-0.33; P < .001), antibodies to infliximab (HR, 0.25; 95% CI, 0.07-0.84; P = .025), and serious infusion reaction (HR, 0.17; 95% CI, 0.04-0.78; P = .023). CONCLUSIONS:In a retrospective analysis of patients with IBD receiving proactive vs reactive monitoring of serum concentration of infliximab, proactive monitoring was associated with better clinical outcomes, including greater drug durability, less need for IBD-related surgery or hospitalization, and lower risk of antibodies to infliximab or serious infusion reactions.

Project description:The Taylor Aggression Paradigm (TAP) has been widely used to measure reactive aggression following provocation during competitive interactions. Besides being reactive, aggression can be goal-directed (proactive aggression). Our study presents a novel paradigm to investigate proactive aggression during competitive interactions. Sixty-seven healthy participants competed in two modified versions of the TAP against an ostensible opponent while skin conductance responses (SCRs) were recorded. During the proactive TAP (pTAP), only the participant could interfere with the ostensible opponent's performance by blurring the screen. In the reactive TAP (rTAP), the opponent repeatedly provoked the participant by blurring the screen of the participant, impeding their chance to win. In both versions, the blurriness levels chosen by the participant served as a measure of aggression (unprovoked in the pTAP and provoked in the rTAP). In the pTAP, trial-by-trial mixed model analyses revealed higher aggression with higher self-reported selfishness. SCRs decreased with increasing proactive aggression. An interaction effect between gender and proactive aggression for the SCRs revealed increased SCRs at higher aggression levels in females, but lower SCRs at higher aggression levels in males. In the rTAP, SCRs were not associated with reactive aggression but aggression increased with increasing provocation and especially after losing against the opponent when provoked. While males showed higher aggression levels than females when unprovoked, reactive aggression increased more strongly in females with higher provocation. Mean levels of aggression in both tasks showed a high positive correlation. Our results highlight that, despite being intercorrelated and both motivated by selfishness, proactive and reactive aggression are differentially influenced by gender and physiological arousal. Proactive aggression is related to lower physiological arousal, especially in males, with females showing the opposite association. Reactive aggressive behavior is a result of individual responses to provocation, to which females seem to be more sensitive.

Dataset Information

Proactive Vs Reactive Therapeutic Drug Monitoring of Infliximab in Crohn's Disease: A Cost-Effectiveness Analysis in a Simulated Cohort.

Background

Methods

Results

Conclusions

Publications

Proactive Vs Reactive Therapeutic Drug Monitoring of Infliximab in Crohn's Disease: A Cost-Effectiveness Analysis in a Simulated Cohort.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure