Cost-utility analysis of second-line therapy with rituximab compared to tumour necrosis factor inhibitors in rheumatoid arthritis.

OBJECTIVE: To compare direct costs and treatment utility associated with the second-line therapy with rituximab and tumour necrosis factor inhibitors (TNFis) (adalimumab, etanercept, and infliximab) in patients with Rheumatoid Arthritis (RA) using data from a prospective registry. METHODS: Health Assessment Questionnaire Disability Index (HAQ-DI) scores and RA-related healthcare resource utilization data (biologic agents and visits to rheumatologists) were extracted from a registry (Quebec, Canada) for patients with RA (n = 129) who had to discontinue a first-line TNFi and were treated with rituximab, adalimumab, etanercept, or infliximab as the second-line therapy between January 2007 and May 2016. A decision analytic model followed patients for 1 and 6 years. Treatment utility was measured as quality-adjusted life-years (QALYs) gained, which were calculated from HAQ-DI scores observed over the follow-up time. Quebec 2020 unit costs (Canadian Dollars, $) were used to value healthcare resource consumption. A probabilistic sensitivity analysis was performed with 10,000 Monte Carlo simulations to assess uncertainty around point-estimates of cost-utility. RESULTS: Over 1-year, rituximab and etanercept resulted in the effectiveness of 0.80 QALYs gained at the cost of $14,291and $18,880, respectively, and were dominant (i.e. associated with lower costs and more QALYs gained) compared to adalimumab (0.79 QALYs, $18,825) and infliximab (0.76 QALYs, $20,158). Over 6-years, rituximab (4.42 QALYs, $82,402) was dominant compared to adalimumab (4.30 QALYs, $101,420), etanercept (4.02 QALYs, $99,191), and infliximab (3.71 QALYs, $100,396). In the probabilistic analysis, rituximab was dominant over adalimumab, etanercept, and infliximab with the probability of 0.51, 0.62, and 0.65, respectively. CONCLUSION: Real-world data revealed differences between alternative biologic agents used as the second-line therapy in terms of both treatment costs for the healthcare system and utility of treatment for patients. Therefore, new guidelines on the order of selecting and switching biologic agents should be explored.

A theoretical exploration of therapeutic monomania as a physician-based instrumental variable.

PURPOSE: To explore the utility of physician prescribing preference as an instrumental variable. METHODS: Expert (non-systematic) review of relevant literature on the appropriate selection of instrumental variables and theoretical exploration of individual physician and physician group prescriber preference. RESULTS: An instrumental variable must satisfy three criteria: (1) It must predict the treatment received (strength of the instrument); (2) it cannot influence the outcome other that through the treatment received (exclusion restriction); and (3) it cannot be influenced by any factor that also influences the outcome (independence assumption). Arguments in favor of prescriber preference as an instrumental variable and suggestions for how to approach specific scenarios that may be encountered are offered. CONCLUSIONS: Prescriber preference, be it of individual physicians or groups of physicians, may, under the right conditions, be powerful instrumental variables. Empiric experimental data are required to determine the appropriateness of combining propensity matching and instrumental variable analysis.

Assessing the risk of multiple sclerosis disease-modifying therapies.

Introduction: The number of immunomodulatory options approved for multiple sclerosis has increased over the past years, resulting in a better control of the disease. Depending on disease activity, neurologists can now propose treatments with different levels of efficacy, from injectable and oral treatments with modest efficacy, to highly active immunosuppressants. Nevertheless, this gain in efficacy has come with an increase in the global burden of treatment-related adverse events. Areas covered: The authors have reviewed extensively the existing literature to gain insight into the adverse events associated with disease modifying therapies, so as to help neurologists choose the right treatment for their patients. The authors classified and summarized the adverse events based on frequency, severity and relevance. Expert opinion: As the number and diversity of adverse events is expected to increase, careful surveillance of patients under treatment will be even more important. The characteristics of the MS population, i.e. mainly young women of childbearing age, who will remain treated for decades, and the need for serial administration of distinct treatments with different mechanisms of action highlights the importance of a comprehensive risk-benefit assessment.

The burden of symptomatic skeletal events in castrate-resistant prostate cancer patients with bone metastases at three Canadian uro-oncology centres.

INTRODUCTION: Metastatic bone disease in castrate-resistant prostate cancer risks significant morbidity, including symptomatic skeletal events. We estimated the healthcare resource costs of managing skeletal events. METHODS: A retrospective chart review was conducted for patients who died from or were treated palliatively for metastatic castrate-resistant prostate cancer from 2006-2013 at Centre Hospitalier de l'Université de Montréal (Montreal), Princess Margaret Cancer Centre (Toronto), or Vancouver General Hospital (Vancouver). RESULTS: Of 393 patients, 275 (70%) experienced 833 events (85 per 100 patient-years), with a median (95% confidence interval) time (months) to first event of 17.6 (15.3, 21.7). The mean metastatic bone disease-related healthcare resource use cost (2014 Canadian dollars) estimate for patients without symptomatic skeletal events was $9550 and between $22 101 (observed) and $34 615 (adjusted) for patients with at least one event. Fewer patients in Montreal (55%) experienced events compared to Toronto (79%) or Vancouver (76%). Median time (months) to first event was longer in Montreal (25.0 [18.5, 32.6]) than in Toronto (14.6 [9.7, 16.8] or Vancouver (17.3 [14.8, 24.0]). More patients received bone-targeted therapy in Montreal (64%) and Toronto (60%) than in Vancouver (24%). Bone-targeted therapy was mostly administered every 3-4 weeks in Montréal and every 3-4 months in Toronto. CONCLUSIONS: Metastatic bone disease-related healthcare resource use costs for Canadian castrate-resistant prostate cancer patients are high. Symptomatic skeletal events occurred frequently, with the incremental cost of one or more events estimated between $12 641 and $25 120. Symptomatic skeletal event incidence and bone-targeted therapy use varied considerably between three Canadian uro-oncology centres. An important limitation is that only patients who died from prostate cancer were included, potentially overestimating costs.

Medication Persistence, Duration of Treatment, and Treatment-switching Patterns Among Canadian Patients Taking Once-daily Extended-release Methylphenidate Medications for Attention-Deficit/Hyperactivity Disorder: A Population-based Retrospective Cohort Study.

PURPOSE: We conducted a retrospective cohort study to compare medication use patterns of a long-acting extended-release methylphenidate (Osmotic Release Oral System [OROS(®)] methylphenidate, CONCERTA(®)) and Teva-methylphenidate (methylphenidate ER-C), a generic drug determined by the Canadian regulatory authority, Health Canada, to be bioequivalent to OROS(®) methylphenidate. METHODS: We established an OROS(®) methylphenidate-experienced and new-user population cohort to compare medication use patterns, including medication persistence, duration of therapy, and treatment-switching patterns. Multivariable log-binomial regression was used to adjust for confounders of the associations with persistence. FINDINGS: In the OROS(®) methylphenidate-experienced cohort (n = 21,940), OROS(®) methylphenidate was associated with a 70% higher rate of medication persistence at 12 months relative to methylphenidate ER-C (adjusted relative risk = 1.70; 95% CI, 1.64-1.77). In the new-user cohort (n = 20,410), OROS(®) methylphenidate had a 58% higher rate of medication persistence relative to methylphenidate ER-C (adjusted relative risk = 1.58; 95% CI, 1.51-1.65). Median duration of therapy was significantly longer in patients taking OROS(®) methylphenidate compared with those taking methylphenidate ER-C, and treatment-switching occurred significantly more frequently in patients taking methylphenidate ER-C compared with those taking OROS(®) methylphenidate. IMPLICATIONS: Significant differences were observed in how the medications were used by patients in the real-world setting. Because the data sources were administrative databases, it was not possible to control for all potentially important confounding variables. Although differences in medication persistence may not directly reflect differences in treatment efficacy, the findings are important because these products are used interchangeably in a number of Canadian provinces.

Effect of cinacalcet availability and formulary listing on parathyroidectomy rate trends.

BACKGROUND: Recent trends in parathyroidectomy rates are not known. Our objective was to investigate the trend in parathyroidectomy rates between 2001 and 2010, and to evaluate if the availability and reimbursement of cinacalcet modified that trend. METHODS: Using a provincial administrative database, we included all adult patients receiving chronic dialysis treatments between 2001 and 2010 (incident and prevalent) in a time series analysis. The effect of cinacalcet availability on parathyroidectomy bimonthly rates was modeled using an ARIMA intervention model using different cut-off dates: September 2004 (Health Canada cinacalcet approval), January 2005, June 2005, January 2006, June 2006 (date of cinacalcet provincial reimbursement), and January 2007. RESULTS: A total of 12 795 chronic dialysis patients (mean age 64 years, 39% female, 82% hemodialysis) were followed for a mean follow-up of 3.3 years. During follow-up, 267 parathyroidectomies were identified, translating to an average rate of 7.0 per 1000 person-years. The average parathyroidectomy rate before cinacalcet availability was 11.4 /1000 person-years, and 3.6 /1000 person-years after cinacalcet public formulary listing. Only January 2006 as an intervention date in the ARIMA model was associated with a change in parathyroidectomy rates (estimate: -5.58, p = 0.03). Other intervention dates were not associated with lower parathyroidectomy rates. CONCLUSIONS: A reduction in rates of parathyroidectomy was found after January 2006, corresponding to cinacalcet availability. However, decreased rates may be due to other factors occurring simultaneously with cinacalcet introduction and further studies are needed to confirm these findings.

Modifiable factors predicting patient survival in elderly kidney transplant recipients.

BACKGROUND: Elderly transplant candidates represent an increasingly important group on the waiting list for kidney transplantation. Yet the factors that determine posttransplantation outcomes in this population remain poorly defined. METHODS: We performed a population-based retrospective cohort study involving all patients aged 60 years or older who received a first cadaveric kidney transplantation between 1985 and 2000 in the province of Quebec. The main outcomes were patient survival, overall graft survival, and treatment failure (patient death or graft loss within the first posttransplant year). Survival analyses were performed using a Cox proportional hazard model. Logistic regression identified factors predicting treatment failure. RESULTS: On multivariate analysis, the modifiable factors associated with patient survival were active smoking at transplantation [hazard ratio (HR) 2.09, 95% confidence interval (CI) 1.22-3.60)], body mass index (BMI) (HR 1.34 for a 5-point increase, 95% CI 1.05-1.67), and time on dialysis before transplantation (HR 1.10 for a 1-year increase, 95% CI 1.02-1.18). The only modifiable factor associated with graft survival was active smoking at transplantation (HR 2.04, 95% CI 1.24-3.30). Treatment failure was associated with time on dialysis before transplantation (odds ratio for dialysis >/=2 years 3.28, 95% CI 1.34-7.9). CONCLUSION: Our results show that active smoking, obesity, and time on dialysis before transplantation are modifiable risk factors associated with an increased risk of mortality after transplantation in elderly recipients. They represent potential targets for interventions aimed at improving patient and graft survival in elderly patients.