Review article: a clinician's guide for therapeutic drug monitoring of infliximab in inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF)-antagonists have an established role in the treatment of inflammatory bowel diseases (IBDs), however, subtherapeutic drug levels and the formation of anti-drug antibodies (ADAs) may decrease their efficacy. AIM: The evidence supporting the use of therapeutic drug monitoring (TDM) based clinical algorithms for infliximab (IFX) and their role in clinical practice will be discussed. METHODS: The literature was reviewed to identify relevant articles on the measurement of IFX levels and antibodies-to-infliximab. RESULTS: Treatment algorithms for IBD have evolved from episodic monotherapy used in patients refractory to all other treatments, to long-term combination therapy initiated early in the disease course. Improved remission rates have been observed with this paradigm shift, nevertheless many patients ultimately lose response to therapy. Although empiric dose optimization or switching agents constitute the current standard of care for secondary failure, these interventions have not been applied in an evidence-based manner and are probably not cost-effective. Multiple TDM-based algorithms have been developed to identify patients that may benefit from measurement of IFX and ADA levels to guide adjustments to therapy. CONCLUSIONS: Therapeutic drug monitoring offers a rational approach to the management of secondary failure to IFX. This concept has gained momentum based on evidence from case series, cohort studies and post-hoc analyses of randomised controlled trials.

Incremental cost-effectiveness analysis comparing rofecoxib with nonselective NSAIDs in osteoarthritis: Ontario Ministry of Health perspective.

BACKGROUND: Clinical trials have shown rofecoxib, a selective inhibitor of cyclo-oxygenase-2, to be associated with fewer gastrointestinal complications than non-selective nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVE: To evaluate the potential clinical and economic consequences of rofecoxib prescription in Ontario, Canada, for patients with osteoarthritis (OA) aged >65 years who did not respond to paracetamol (acetaminophen) therapy. DESIGN: Decision analytic modelling study. METHODS: A model was constructed to compare rofecoxib and nonselective NSAIDs with respect to their gastrointestinal complications in patients with OA. The model had a 1-year horizon and considered direct medical costs from the perspective of the Ontario Ministry of Health. Event rates were estimated from a pooled analysis of 8 phase IIb/Ill clinical trials. The number of perforations, ulcers and bleeds (PUBs) with each strategy was used as the primary measure of effectiveness. RESULTS: In the base-case scenario, the expected total cost per patient-day on nonselective NSAIDs was 1.60 Canadian dollars (Can dollars) versus 1.67 Can dollars on rofecoxib (1999 values). Rofecoxib was associated with 0.0109 fewer PUBs per patient per year. The incremental cost to avoid 1 additional PUB by substituting rofecoxib for nonselective NSAIDs was 2247 Can dollars. The rofecoxib strategy became dominant if a gastroprotective agent was prescribed to more than 27.5% of the patients receiving nonselective NSAIDs. CONCLUSION: For patients with OA aged >65 years in whom paracetamol therapy has failed, rofecoxib may represent a cost-effective alternative to nonselective NSAIDs. Increased costs for drug acquisition are offset, in part. by avoidance of gastrointestinal complications and reduced use of gastroprotective agents. Rofecoxib may offer increased benefit among patients at a higher risk of serious gastrointestinal events.

Test and treat strategies for Helicobacter pylori in uninvestigated dyspepsia: a Canadian economic analysis.

BACKGROUND: Recognition of the pivotal role of Helicobacter pylori in the pathogenesis of peptic ulcer disease has revolutionized primary care approaches to dyspepsia. Decision analysis was used to compare the cost effectiveness of empirical ranitidine with a test and treat strategy using either H pylori serology or the 13carbon-urea breath test (13C-UBT). PATIENTS AND METHODS: A cohort of patients under age 50 years presenting with uninvestigated dyspepsia was evaluated. Three initial strategies were compared with respect to direct medical costs and effectiveness in curing H pylori-related ulcers - empirical ranitidine, H pylori serology and UBT. A one-year time horizon and third-party payer perspective were adopted in a Canadian health care setting. RESULTS: UBT was more costly than either serology or ranitidine but was the most effective strategy and required the fewest endoscopies. No strategy demonstrated dominance over another in the base case. The incremental cost effectiveness ratio (ICER) of serology versus ranitidine was $118/cure, and sensitivity analysis induced dominance of serology in several plausible scenarios. The baseline ICER of UBT versus serology was $885/cure but showed substantial variation in sensitivity analysis. Each ICER was highly sensitive to variation in the cost of the tests themselves. At a serology cost of $25, UBT became dominant when its cost fell to $39. CONCLUSIONS: In low risk patients with uninvestigated dyspepsia, testing for H pylori using serology appears to be economically attractive. 13C-UBT may be a cost effective alternative to serology if local conditions closely approximate the model parameters. Future changes in the costs of serology and 13C-UBT may determine the optimal approach.

Demographic predictors of resource utilization for bleeding peptic ulcer disease: the Ontario GI Bleed Study.

Peptic ulcer disease (PUD) and its complications impose a substantial burden on health care resources. To help identify subpopulations in which preventative measures might achieve maximal cost savings, the authors studied the variation in resource utilization and cost for management of bleeding PUD among demographic subgroups. Resource utilization profiles and direct medical cost estimates were generated for consecutive admissions for bleeding PUD at four hospitals in southern Ontario via chart review and adaptation of an administrative cost database. Multiple linear regression models were developed to identify independent demographic predictors of direct medical case cost and hospital length of stay (LOS). Among 158 admissions, the average LOS and case costs were 5.73 days and $2,953 (Canadian) respectively. Age, comorbid illness, nonsteroidal anti-inflammatory drug use, and the absence of prior PUD or upper gastrointestinal hemorrhage were associated with higher cost in univariate analysis, whereas increasing age and comorbidity predicted LOS. Only age and absence of prior PUD persisted as independent predictors of direct medical cost and LOS in a stepwise multiple linear regression. Costs for managing bleeding PUD vary substantially among demographic subgroups. More careful stratification of treatment costs is needed when economic models of interventions to prevent or to treat PUD are applied to specific subpopulations.

Prediction of resource utilization and case cost for acute nonvariceal upper gastrointestinal hemorrhage at a Canadian community hospital.

OBJECTIVE: Upper gastrointestinal hemorrhage (UGIH) is common, and thus imposes a substantial burden on health care resources. We describe resource utilization and cost for management of acute nonvariceal UGIH, and studied their variation among population subgroups. METHODS: Resource utilization and direct medical case costs were extracted for consecutive admissions for nonvariceal UGIH at a large community hospital in southern Ontario through chart review and adaptation of an administrative case cost database. Univariate and multiple regression models were then developed to identify independent demographic predictors of case cost and length of stay. RESULTS: Among 116 eligible admissions the average length of stay and case cost were 4.26 days and Can$2690, respectively (Can$1 = US$0.70). Both cost and length of stay demonstrated significant univariate relationships with age, comorbid illness, prior peptic ulcer disease (PUD), and prior UGIH. Age and prior PUD persisted as independent predictors in multiple regression models. An inverse transformation of total case cost allowed these variables to explain 26% of the total variance. CONCLUSIONS: Resource utilization for management of acute nonvariceal UGIH at a Canadian community hospital varies substantially among population subgroups, but correlates independently with age and prior ulcer history. Careful attention must be paid to practice environments and demographic profiles before economic models of strategies to prevent or treat UGIH are applied to specific subpopulations.