Cost-effectiveness analysis of dupilumab among patients with oral corticosteroid-dependent uncontrolled severe asthma in Japan.

BACKGROUND: Asthma is a common, chronic inflammatory airway disorder, with up to 1,177,000 people receiving asthma treatment in Japan. Dupilumab is a first-in-class, monoclonal antibody for the treatment of atopic diseases, including persistent asthma. The objective of this study was to assess the cost-effectiveness of dupilumab, compared with other biologics, as add-on treatment to background therapy in patients aged ≥12 years with uncontrolled, persistent asthma in Japan. METHODS: A life-time Markov cohort model was used to conduct cost-effectiveness analysis from the Japanese healthcare payer perspective with an annual discount rate of 2%. Dupilumab was compared with benralizumab and mepolizumab, and against omalizumab (as a hypothetical scenario). Inputs were informed by dupilumab clinical trials (VENTURE [NCT02528214] and QUEST [NCT02414854] trials), the literature, official Japanese sources and expert opinions. RESULTS: The base case results suggest that treatment with dupilumab leads to fewer severe exacerbations and increased life-years (LYs) and quality-adjusted LYs (QALYs) than benralizumab and mepolizumab. At a willingness-to-pay (WTP) threshold of ¥5,000,000 per QALY gained, dupilumab was the dominant strategy (lower cost, increased QALYs) versus benralizumab, and cost-effective versus mepolizumab with an incremental cost-effectiveness ratio (ICER) of ¥1,010,921 (US$9,190, US$1 = ¥110). Versus omalizumab, dupilumab was not cost-effective (ICER of ¥10,802,368 [US$98,203]). CONCLUSIONS: In Japan, dupilumab, as an add-on to background therapy, is economically dominant compared with benralizumab, and cost-effective versus mepolizumab.

Cost-Effectiveness of Alirocumab in Patients With Acute Coronary Syndromes: The ODYSSEY OUTCOMES Trial.

BACKGROUND: Cholesterol reduction with proprotein convertase subtilisin-kexin type 9 inhibitors reduces ischemic events; however, the cost-effectiveness in statin-treated patients with recent acute coronary syndrome remains uncertain. OBJECTIVES: This study sought to determine whether further cholesterol reduction with alirocumab would be cost-effective in patients with a recent acute coronary syndrome on optimal statin therapy. METHODS: A cost-effectiveness model leveraging patient-level data from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was developed to estimate costs and outcomes over a lifetime horizon. Patients (n = 18,924) had a recent acute coronary syndrome and were on high-intensity or maximum-tolerated statin therapy, with a baseline low-density lipoprotein cholesterol (LDL-C) level ≥70 mg/dl, non-high-density lipoprotein cholesterol ≥100 mg/dl, or apolipoprotein B ≥80 mg/l. Alirocumab 75 mg or placebo was administered subcutaneously every 2 weeks. Alirocumab was blindly titrated to 150 mg if LDL-C remained ≥50 mg/dl or switched to placebo if 2 consecutive LDL-C levels were <15 mg/dl. Incremental cost per quality-adjusted life-year (QALY) was determined with the addition of alirocumab versus placebo and, based on clinical efficacy findings from the trial, was stratified by baseline LDL-C levels ≥100 mg/dl and <100 mg/dl. RESULTS: Across the overall population recruited to the ODYSSEY OUTCOMES trial, using an annual treatment cost of US$5,850, the mean overall incremental cost-effectiveness ratio was US$92,200 per QALY (base case). The cost was US$41,800 per QALY in patients with baseline LDL-C ≥100 mg/dl, whereas in those with LDL-C <100 mg/dl the cost per QALY was US$299,400. Among patients with LDL-C ≥100 mg/dl, incremental cost-effectiveness ratios remained below US$100,000 per QALY across a wide variety of sensitivity analyses. CONCLUSIONS: In patients with a recent acute coronary syndrome on optimal statin therapy, alirocumab improves cardiovascular outcomes at costs considered intermediate value, with good value in patients with baseline LDL-C ≥100 mg/dl but less economic value with LDL-C <100 mg/dl. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402).

Aflibercept Plus FOLFIRI vs. Placebo Plus FOLFIRI in Second-Line Metastatic Colorectal Cancer: a Post Hoc Analysis of Survival from the Phase III VELOUR Study Subsequent to Exclusion of Patients who had Recurrence During or Within 6 Months of Completing Adjuvant Oxaliplatin-Based Therapy.

The aim of this post hoc analysis of the VELOUR study (ClinicalTrials.gov NCT00561470) was to investigate the treatment effect of adding aflibercept to second-line infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) in patients with metastatic colorectal cancer (mCRC) who had failed any prior oxaliplatin-containing regimen. Adjuvant rapid relapsers (ARR), who were enrolled directly following relapse during or within 6 months of completion of oxaliplatin-containing adjuvant chemotherapy (N = 124, including 17 patients who also received bevacizumab as part of their adjuvant therapy), were excluded from the original VELOUR intention-to-treat (ITT) population (N = 1226). After exclusion of the ARR, overall survival (OS) in the ITT minus ARR (ITT-ARR) population (N = 1102) was longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm [hazard ratio (HR) 0.78, 95 % confidence interval (CI) 0.68-0.90; median survival difference 1.87 months]. In the subgroup of patients assigned to the prior bevacizumab stratum at randomization, OS was numerically longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm (HR 0.81; 95 % CI 0.63-1.04; median survival difference 2.14 months). Comparison of the post hoc analysis results with the primary analysis from VELOUR suggests that the inclusion of the directly enrolled ARR may have understated the aflibercept treatment benefit for both bevacizumab-pretreated and bevacizumab-naïve patients in the strictly second-line setting although no definitive conclusion may be inferred. The benefit associated with the addition of aflibercept to second-line FOLFIRI in patients with mCRC was observed whatever the timing of first-line disease progression. There were no unexpected safety concerns.

A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI.

BACKGROUND: The VELOUR study demonstrated a survival benefit for FOLFIRI + aflibercept versus FOLFIRI + placebo in metastatic colorectal cancer (mCRC) patients who progressed on oxaliplatin-based chemotherapy. Continued divergence of overall survival (OS) curves in the intension to treat (ITT) population, with the survival advantage persisting beyond median survival time, suggested subpopulations might have different magnitudes of survival gain. Additionally, 10% of patients within VELOUR had recurrence during or within 6 months of completing oxaliplatin-based adjuvant therapy (adjuvant fast relapsers)--previously identified as having poorer survival outcomes. METHODS: To determine which patients received the greatest benefit from FOLFIRI-aflibercept, a post hoc multivariate analysis of the VELOUR ITT population was conducted. Prognostic factors identified were applied to the ITT population, excluding adjuvant fast relapsers, to derive OS prognostic profiles. RESULTS: The better efficacy subgroup was identified as patients within VELOUR exclusive of adjuvant fast relapsers and had performance status (PS) 0 with any number of metastatic site or PS 1 with <2 metastatic site. A significant improvement in efficacy outcome was observed with aflibercept in the better efficacy subgroup. Median OS for FOLFIRI-aflibercept and FOLFIRI-placebo:16.2 and 13.1 months (adjusted Hazard Ratio [HR] = 0.73; 95% confidence interval [CI]: 0.61-0.86); median progression free survival (PFS): 7.2 and 4.8 months (adjusted HR = 0.68; 95% CI: 0.57-0.80); and objective response rate (ORR): 24% versus 11% respectively. Poorer efficacy subgroup comprised of adjuvant fast relapsers or patients with PS2 or PS1 with ≥ 2 metastatic sites. In poorer efficacy subgroup, no benefit was seen with aflibercept. Median OS for FOLFIRI-aflibercept and FOLFIRI-placebo: 10.4 and 9.6 months (adjusted HR = 0.97; 95% CI: 0.78-1.21) respectively with no improvement in PFS or ORR. CONCLUSION: This analysis suggests that within VELOUR, patients in the better efficacy subgroup may derive enhanced benefit from treatment with FOLFIRI-aflibercept. These prognostic criteria may guide practitioners toward optimal use of targeted biologicals in appropriate second-line mCRC patients.

Development and validation of the self-completed ascites impact measure to understand patient motivation for requesting a paracentesis.

BACKGROUND: The Ascites Impact Measure (AIM) was developed to record patients' daily experiences of symptoms that trigger a request for a paracentesis. METHODS: Development of the AIM followed a rigorous step-wise approach, including a review of the literature, expert opinions, and qualitative research involving patients who experience symptomatic malignant ascites. The AIM's measurement properties were assessed using data from two international trials, including 59 ovarian cancer patients with symptomatic malignant ascites. RESULTS: Following the literature review and expert discussions to develop the conceptual model, ten patients with symptomatic malignant ascites were interviewed in the item elicitation phase, resulting in a draft questionnaire with four questions. Validation analyses consisted of 59 patients pooled from two international trials. Inter-items correlations for the AIM were good (r > 0.60), except for the Pain item. Internal consistency reliability (α = 0.89) improved after removing the Pain item from the Total Symptom score (TSS). Test-retest reliability was sufficient. Scores significantly improved after paracentesis except for the Pain item. Preliminary estimates indicate that a two-point improvement on the three-item TSS (without the Abdominal Pain item) could be interpreted as clinically meaningful. CONCLUSION: The Abdominal Pain item appears to behave differently than the other three items, and could be more related to cancer. While the validity of the AIM TSS (four-item) is acceptable, removing the Pain item from the TSS scoring algorithm demonstrated better construct validity. In addition, test-retest reliability and responsiveness were found to be similar to the results for the four-item AIM TSS. The Pain item should be used as a supplemental item to the three-item AIM TSS, as it provides additional information about the underlying cancer state.

The role of gender and other factors as predictors of not receiving reperfusion therapy and of outcome in ST-segment elevation myocardial infarction.

BACKGROUND: The standard of care for ST-segment elevation myocardial infarction (STEMI) is prompt coronary reperfusion with thrombolysis or percutaneous coronary intervention. Women have higher mortality rates than men following STEMI and fewer women are considered eligible for reperfusion therapy. We analyzed the impact of gender, and other factors, on the outcome and treatment of STEMI in the TETAMI trial and registry. METHODS: This exploratory analysis included 2741 patients from Treatment with Enoxaparin and Tirofiban in Acute Myocardial Infarction (TETAMI) presenting with STEMI within 24 hours of symptom onset. The primary composite end point was the combined incidence of all-cause death, recurrent myocardial infarction, and recurrent angina, at 30 days. Three multivariate analyses were performed to determine predictors of not receiving reperfusion therapy, the composite end point, or death. RESULTS: The triple end point occurred in 17.8% of women versus 13.3% of men. Reperfusion therapy was utilized in 38.2% of women versus 47.3% in men. However, age > 75 years, delayed presentation, high systolic blood pressure (> 100) and region (South Africa), were significant, independent predictors of not receiving reperfusion therapy. Significant predictors of the triple end point included not receiving reperfusion therapy, age > 60 years, and higher Killip class. Predictors of death included age > 60 years, low systolic blood pressure, higher Killip class, high heart rate, delayed presentation, and region (South Africa and South America). CONCLUSION: Female gender was not an independent predictor of outcome or underutilization of reperfusion therapy. Factors more common in female STEMI patients (advanced age and delayed presentation) were associated with not receiving reperfusion therapy and adverse outcome. Increased awareness is needed to reduce delayed presentation after symptom onset, especially among women. Abbreviated abstract. In this analysis of 2741 ST-segment elevation myocardial infarction patients in the TETAMI trial and registry, a trend was observed for women being less likely to receive reperfusion therapy and more likely to have an adverse outcome than men. This was related to factors more common in female patients (advanced age and delayed presentation), and showed that an increased awareness is needed to reduce delayed presentation after symptom onset, especially among women.