Ariel Hammerman

Antipsychotics and Diabetes: An Age-Related Association

Background Previous studies have reported an association between antipsychotic medications and diabetes. Objective To explore the association between antipsychotic medications and diabetes in patients of different ages. Methods A retrospective analysis of a large health maintenance organizations drug claim database (3.7 million members) was performed. All patients treated with antipsychotic drugs during 1998–2004 were identified. Patients with diabetes were defined by a record of antidiabetic drug uso during 2004. The prevalence of diabetes in different age groups treated with antipsychotics was compared with the prevalence of diabetes among enrollees in the same age groups not treated with antipsychotics. Results: Among 82,754 patients treated with antipsychotics, the association between diabetes and consumption of antipsychotics was strongest in the younger age groups and decreased with increasing age: for patients aged 0–24 years, OR 8.9 (95% CI 7.0 to 11.3); 25–44 years, OR 4.2 (95% CI 3,8 to 4.5); 45–54 years, OR 1.9 (95% CI 1.8 to 2.1); 55–64 years, OR 1.3 (95% CI 1.2 to 1.4); and 65 years or older, OR 0.93 (95% CI 0.9 to 1.0). However, the risk associated with atypical antipsychotics was lower than the risk associated with typical antipsychotics, with ORs ranging from 0.7 in patients 0–24 years old to 0.3 in those 65 years or older. Conclusions: Antipsychotic drug use was associated with diabetes mellitus. This association was stronger in younger patients. In older adults, the difference was much smaller and, in some cases, there was no association. A lowor risk was associated with atypical agents, as compared with typical antipsychotics. Clinicians should bo aware that young adults treated with antipsychotics are at increased risk for diabetes.

Systemic Therapy for Psoriasis and the Risk of Herpes Zoster: A 500 000 Person-year Study

IMPORTANCE The risk for herpes zoster (HZ) in patients with psoriasis treated with biologic medications or other systemic treatments has been given little attention to date. OBJECTIVE To describe the risk for HZ in patients with psoriasis and its relation to treatment. DESIGN, SETTING, AND PARTICIPANTS A cohort study was performed using the administrative database of Clalit Health Services, the largest public health care provider organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. We extracted information for all patients who received a psoriasis diagnosis from January 2002 to June 2013. Follow-up was conducted until the end of July 2013. The study included 95,941 patients with psoriasis in the analysis, with 522,616 person-years of follow-up. Incidence of HZ events was calculated for each systemic antipsoriatic medication provided, during a follow-up period of 11 years and 7 months. We used a generalized estimating equation Poisson regression model to examine the effect of each systemic treatment for psoriasis on HZ incidence, adjusting for age, sex, psoriasis severity, Charlson comorbidity index, steroid treatment, and socioeconomic status. MAIN OUTCOMES AND MEASURES Incidence of HZ associated with systemic therapies. RESULTS In a multivariate analysis, it was observed that treatment with phototherapy (rate ratio [RR], 1.09 [95% CI, 0.62-1.93]; P = .99), methotrexate (RR, 0.98 [95% CI, 0.78-1.23]; P = .83), cyclosporine (RR, 1.16 [95% CI, 0.48-2.80]; P = .49), and biologic medications as a single agent (RR, 2.67 [95% CI, 0.69-10.3]; P = .14) was not associated with HZ. The use of combination treatment with biologic medications and methotrexate was significantly associated with an increased incidence of HZ (RR, 1.66 [95% CI, 1.08-2.57]; P = .02). The use of acitritin was associated with decreased incidence of HZ (RR, 0.69 [95% CI, 0.49-0.97]; P = .004). CONCLUSIONS AND RELEVANCE Physicians may need to consider offering an HZ preventive vaccine to patients receiving combination treatment with biologic medications and methotrexate, particularly if they have additional risk factors for HZ.

Bleeding in patients with atrial fibrillation treated with dabigatran, rivaroxaban or warfarin: A retrospective population-based cohort study

BACKGOUND Randomized controlled trials (RCTs) have shown that dabigatran, rivaroxaban and warfarin cause similar bleeding rates. METHODS We performed a retrospective population-based cohort study to determine the incidence of bleeding in patients with atrial fibrillation (AF) beginning dabigatran, rivaroxaban or warfarin. Consecutive patients initiating anticoagulation for AF during a 3year period were identified using a computerized database. Patients who bled and required hospitalization underwent chart review. Bleeding incidences were calculated per 100 patient-years of treatment. RESULTS 18,249 patients were included: 9564 (52.4%) received warfarin, 5976 (32.7%) dabigatran, and 2709 (14.8%) rivaroxaban. Bleeding incidences were 3.9 (95% CI, 3.6-4.4) in warfarin-treated patients, 4.2 (95% CI, 3.7-4.7) in dabigatran patients, and 4.1 (95% CI, 3.0-5.3) in rivaroxaban patients. Intracranial hemorrhage (ICH) rates were 0.71 (95% CI, 0.56-0.90) for warfarin, 0.4 (95% CI, 0.18-0.87) for dabigatran, and 0.27 (95%CI, 0.10-0.80) for rivaroxaban. GI hemorrhage rates were 1.88 (95%CI, 1.62-2.20) for warfarin, 2.98 (95% CI, 2.4-3.5) for dabigatran and 2.39 (95%CI, 1.6-3.5) for rivaroxaban. CONCLUSIONS We demonstrate similar bleeding rates with both dabigatran 150mg and 110mg and rivaroxaban compared to warfarin.

Oncologists' and family physicians' views on value for money of cancer and congestive heart failure care.

BackgroundPrevious studies suggest that cancer-related interventions are valued by policy makers more favorably than interventions for other medical conditions, but the views of practicing physicians have not yet been assessed in Israel. Attitudes and judgments of practicing physicians may assist decision-makers in their deliberations on coverage of new technologies. We conducted a national survey in Israel among oncologists and family physicians to explore their views on access to care, coverage decisions and treatment recommendations for cancer and congestive heart failure (CHF) patients.MethodsWe administered a web-based survey to 300 family physicians and 156 oncologists. The questionnaire included 24 statements and physicians were asked to indicate their level of agreement with each statement on a 5-point Likert scale, ranging from “strongly agree” to “strongly disagree”. Where relevant, physicians were asked to express their views on interventions for cancer and CHF respectively.ResultsResponse rates were 39% for family physicians and 36% for oncologists. Participants expressed similar views on cancer and CHF care and no significant differences were found between the two medical specialties. More than 85% of physicians believe that inclusion of a treatment in the National List of Health Services (NLHS) strongly affects their patients’ access to care. Approximately 80% suggest that more use of comparative-effectiveness and cost-effectiveness analysis is needed in coverage decisions. The vast majority of respondents (75%) suggest that assessment of value-for-money should be made by an independent (academic) institution or the national committee responsible for recommending coverage decisions, Seventy percent believe that treatments not included in the NLHS should be included in supplementary health insurance programs and only a small minority of respondents (<30%) believe that cancer-related interventions should receive higher priority than non-cancer interventions in coverage decisions.ConclusionsOur findings suggest that both oncologists and family physicians value cancer and CHF interventions equally. We could not find evidence for a “cancer premium” as implied from previous surveys and analysis of coverage decisions in various countries.

PCSK9 inhibitors may improve cardiovascular outcomes-Can we afford them?

BACKGROUND/OBJECTIVES Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) can significantly lower low-density lipoprotein (LDL) cholesterol levels. Early evidence suggests that use of PCSK9i also reduces the incidence of major adverse cardiovascular events (MACE). Our objective was to determine preliminary economic implications of PCSK9i use to avoid MACE, based on the current data from major phase III clinical trials. METHODS Outcome data of the 4529 patients treated with PCSK9i in the OSLER and ODYSSEY LONG TERM trials were collected from the published reports. Cost of preventing MACE was evaluated based on the existing outcome data and current US prices of PCSK9i. The pooled results were compared to the cost of curing Hepatitis C Virus (HCV) patients with novel HCV drugs. RESULTS PCSK9i treatment in the OSLER and ODYSSEY LONG TERM trials resulted in prevention of 35 MACE in a total of 4903 patient-years: 8 cardiovascular deaths, 22 myocardial infarctions, 0 strokes and 5 unstable anginas. The cost of PCSK9i drugs consumed during the trials current follow-up period, could have reached

The 'real-life' impact of adding bevacizumab to first-line therapy in metastatic colorectal cancer patients: a large Israeli retrospective cohort study.

70,172,141. Therefore, the cost of preventing any MACE would be

The ESMO-Magnitude of Clinical Benefit Scale for novel oncology drugs: correspondence with three years of reimbursement decisions in Israel

2,004,918 and the cost of preventing one death would be

Effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir for hepatitis C virus in clinical practice: A population-based observational study

8,777,518. These figures are one hundred fold higher than the cost of curing one HCV patient (~

Effectiveness and safety of nivolumab in advanced non-small cell lung cancer: the real-life data

84,000). CONCLUSIONS According to the current published data, using PCSK9i to prevent MACE seems to be a very expensive strategy. If upcoming outcome trials will demonstrate similar results, it seems that at current prices, using these drugs would not be affordable for most healthcare systems.

Bevacizumab for Metastatic Colorectal Cancer: A Global Cost‐Effectiveness Analysis

Abstract Background. After a decade of extensive use, the actual contribution of bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC) is still unclear. Objective. To evaluate ‘real-life’ outcomes of patients with mCRC before and after the introduction of bevacizumab to standard mCRC first-line practice. Methods. Using the computerized administrative database of Clalit Health Services’ (CHS), Israels largest health care provider, we retrospectively compared two cohorts (n = 1739): (A) all CHS’ patients diagnosed with mCRC between January 2000 and December 2004 that received first-line irinotecan or oxaliplatin-based combination chemotherapy (before bevacizumab was introduced) (n = 1052), and (B) all patients that started first-line irinotecan or oxaliplatin combination chemotherapy together with bevacizumab between September 2006 and December 2009 (after bevacizumab was fully reimbursed in Israel for mCRC first-line therapy) (n = 687). The primary endpoint was overall survival (OS) and secondary endpoints were first-line progression-free survival (PFS) and metastatectomy rates. Results. Median OS was longer in Cohort B than in Cohort A [23.0 months vs.15.0, adjusted hazard ratio (HR), 0.75]. Secondary outcomes were also better; PFS of 14.0 months vs. 9.8 in the earlier period (HR, 0.75) and metastatectomy rate of 8.1% versus 3.9%. The longer OS in Cohort B was preserved even after controlling for latter-line epidermal growth factor receptor (EGFR) inhibitor use (HR = 0.77). Conclusion. In this analysis, OS, PFS and metastatectomy rates of first-line treatment of mCRC were significantly higher in the later period of the study. These results, derived from ‘real-life’ practice, suggest that the use of bevacizumab, among other alterations in the clinical management of mCRC between the two periods, might have had a significant contribution to these outcomes, and may therefore support the current practice of adding bevacizumab to first-line treatment of mCRC.