A Cost-Utility Analysis of Add-On Cannabidiol Versus Usual Care Alone for the Treatment of Seizures Associated with Tuberous Sclerosis Complex in England and Wales.

OBJECTIVES: The aim of this study was to evaluate the cost effectiveness of plant-derived highly purified cannabidiol (Epidyolex® in the UK; 100 mg/mL oral solution) as an add-on treatment to usual care for the management of treatment-refractory seizures associated with tuberous sclerosis complex (TSC) in patients aged ≥ 2 years. METHODS: A cohort-based model was developed using a National Health Service perspective and lifetime horizon. Health states were based on weekly seizure frequency and seizure-free days, utilizing patient-level data from the GWPCARE6 trial (ClinicalTrials.gov identifier: NCT02544763). Two independent regression models were applied to individual patient-level data to predict seizure-free days and seizure frequency. Healthcare resource utilization data were sourced from a Delphi panel, and patient and caregiver health-related quality of life values were elicited using vignettes valued by the general public. Outcomes relating to TSC-associated neuropsychiatric disorders were modeled with costs and quality-adjusted life-years sourced from published literature. RESULTS: In the base case, compared with usual care alone, 12 mg/kg/day cannabidiol was associated with an incremental cost-effectiveness ratio (ICER) of £23,797. The National Institute for Health and Care Excellence disease severity modifier reduced the ICER to £19,831. Probabilities of cost effectiveness at willingness-to-pay thresholds of £20,000 and £30,000 were 30% and 52%, respectively, for the base case and 39% and 66%, respectively, for the disease severity modifier. Results were robust to sensitivity and scenario analyses. CONCLUSIONS: At 12 mg/kg/day and an ICER threshold of £20,000-£30,000, we provide evidence for the cost effectiveness of add-on cannabidiol treatment for patients with TSC-associated seizures aged ≥ 2 years who are refractory to current treatment.

Comparative efficacy, quality of life, safety, and tolerability of atogepant and rimegepant in migraine prevention: A matching-adjusted indirect comparison analysis.

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1-12. RESULTS: There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1-12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: -1.65 [-2.49, -0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. CONCLUSION: In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

Indirect treatment comparison of nivolumab versus placebo for the adjuvant treatment of melanoma.

INTRODUCTION: Until recently, adjuvant treatment options for stage III and IV resectable melanoma have been limited. Patients were often managed through routine surveillance. The phase III randomised controlled trial (RCT) CheckMate 238 (238) demonstrated the safety and efficacy of nivolumab as an adjuvant treatment for melanoma in patients with stage IIIB/C or IV disease (American Joint Committee on Cancer [AJCC], 7th edition) versus ipilimumab. The study objective was to estimate the relative efficacy, safety and health-related quality of life (HRQoL) between nivolumab and routine surveillance. METHODS: Indirect treatment comparisons (ITCs) of nivolumab versus placebo were constructed using data from 238 and EORTC 18071. EORTC 18071 is a phase III RCT comparing ipilimumab with placebo in patients with resected stage IIIA-IIIC melanoma (AJCC, 6th edition). ITCs were performed using the Bucher comparison method and patient-level data for efficacy, safety and HRQoL. RESULTS: For the efficacy outcomes, nivolumab performed significantly better than placebo for recurrence-free survival (hazard ratio [HR]: 0.53 [95% confidence interval {CI}: 0.41, 0.68]) and distant metastases-free survival (HR: 0.59 [95% CI: 0.44, 0.78]). Safety ITCs indicated that patients receiving nivolumab had a greater hazard of experiencing an adverse event (AE) and AEs leading to treatment discontinuation, whereas there was a non-significant increased hazard of experiencing a serious AE. HRQoL ITCs showed comparable time to deterioration in 14 of the 15 QLQ-C30 domains; only the dyspnoea domain significantly favoured placebo. CONCLUSION: Nivolumab was associated with significantly improved efficacy outcomes versus placebo, whereas maintaining patient's overall HRQoL. Across the different analysis and populations, there was a high level of consistency in the effect size.

Modelling Survival of Patients Treated with Adjuvant Nivolumab Who Have Melanoma with Lymph Node Involvement or Metastatic Disease After Complete Resection.

INTRODUCTION: Nivolumab demonstrated significant recurrence-free survival (RFS) gains versus ipilimumab in the CheckMate-238 trial, whereas the CA184-029 trial showed superior RFS gains for ipilimumab versus placebo. No head-to-head trial data were available to compare the efficacy of nivolumab to that of observation, so indirect treatment comparisons were required. Additionally, overall survival (OS) data were not available from CheckMate-238, and the clinical pathway for melanoma has changed significantly over the last decade. Four modelling options were developed using different methods and evidence sources to estimate OS and the impact of nivolumab on predicted life-years in the adjuvant setting; however, this article focuses on two primary methods. METHODS: RFS for nivolumab and observation were informed by a patient-level data meta-regression. The first model was a partitioned survival model, where the parametric OS curve for observation was derived from CA184-029 and nivolumab OS was based on a surrogacy relationship between RFS and OS specific to adjuvant melanoma. The other option used a state-transition model to estimate post-recurrence survival using different data sources. RESULTS: The modelling options estimated different OS for both nivolumab and observation but demonstrated at least a 32% increase in life-years gained for nivolumab versus observation. CONCLUSION: This analysis demonstrated the difficulties in modelling within the adjuvant setting. Each model produced different survival projections, showing the need to explore different techniques to address the extent of uncertainty. This also highlighted the importance of understanding the impact of RFS in the long term in a setting where the aim of treatment is to remain disease free.

The impact of home parenteral nutrition on the burden of disease including morbidity, mortality and rate of hospitalisations.

INTRODUCTION: Home parenteral nutrition (HPN) provides fluid and nutrition essential for the survival of patients with type 3 intestinal failure (IF). However, it is associated with complications and re-admission to hospital. This study aims to investigate the effect of HPN on mortality, morbidity and hospital re-admissions. METHOD: This is a retrospective cohort study. All patients newly dependent on HPN discharged over a 4-year period between 2011 and 2015 were included. Patients' characteristics, nutritional status and diagnosis were recorded, along with frequency and duration of HPN administration. Outcomes collected included hospital re-admissions, morbidity, catheter related blood stream infections (CRBSIs) and mortality. Regression analyses were performed to estimate the rate of different outcomes adjusted for prognostic factors. RESULTS: There were 210 patients included, 561 separate HPN prescriptions equating to 110,537 catheter days. Total number of deaths was 44 (0.398 deaths per 1000 catheter days). There were 196 re-admissions to hospital recorded for a total of 5594 days, 69 (33%) of these re-admissions were unplanned (2484 days in hospital). Principle reasons for unplanned re-admissions included: CRBSIs (n = 31, 45%); other sepsis (n = 10, 14.5%) and abdominal symptoms (n = 9, 13%). CRBSIs were recorded in 22 (10%) patients, equating to a rate of 0.199 per 1000 catheter days. Days per week on HPN increased the relative rate (RR) of time in hospital due to any reason or for unplanned readmissions, RR 1.50 (95% CI: 1.26, 1,78 p < 0.001) and RR 1.39 (95% CI: 1.10, 1.75 p = 0.006) respectively. However, there was no association between days per week on HPN and CRBSI occurrence. CONCLUSION: Unplanned re-admissions for patients with IF accounted for a third of all hospitalisations in those on HPN and the majority were due to CRBSI. The number of HPN dependent days per week was related to all-cause unplanned re-admissions, although not to CRBSI rate.

A new modeling approach allowing prediction and comparison of the long-term outcomes of treatments for hemophilia B.

AIM: To develop a modeling approach to compare clinical outcomes of nonacog beta pegol to a standard-acting factor IX (FIX) product. METHODS: Regression analysis linked FIX activity to bleed rates. Pharmacokinetic parameters were used to estimate FIX activity over time. The probability of bleeds was estimated for both treatment arms. A Markov model estimated the presence of target joints and annualized bleed rates (ABRs). RESULTS: Higher FIX activity showed reduced ABRs (p < 0.001). Target joints resulted in higher bleed rates (p < 0.001). When FIX activity levels and bleed risks were applied to the Markov model, ABRs for nonacog beta pegol and its comparator were 2.40 and 6.36, respectively. CONCLUSION: This model provides a starting point for assessing the added value of new FIX products.