Treatment patterns and outcomes for patients with unresectable stage III and metastatic melanoma in the USA.

Aim: To describe treatment patterns and outcomes of patients with unresectable stage III and metastatic/stage IV melanoma. Materials & methods: An observational retrospective chart review of patients diagnosed with advanced melanoma before 1 November 2015 who initiated a new line of therapy (LOT) from 1 January 2015 to 31 May 2016.  Results: Among 487 patients, ipilimumab monotherapy (27.5%) was the most common first line of therapy (1LOT) in 2015, surpassed by nivolumab monotherapy (21.5%) in 2016. 12-month survival was ≥80.1%; proportions were highest forpatients treated with nivolumab + ipilimumab (86.6%). All treatments relatively well tolerated in real-world setting and adverse events were consistent with the previously reported safety profiles. Conclusion: This study provides important insights into real-world advanced melanoma treatment patterns and demonstrates encouraging treatment safety and patient survival data.

Understanding the Disease Course and Therapeutic Benefit of Tafamidis Across Real-World Studies of Hereditary Transthyretin Amyloidosis with Polyneuropathy: A Proof of Concept for Integrative Data Analytic Approaches.

INTRODUCTION: Hereditary transthyretin (TTR) amyloidosis with polyneuropathy (hATTR-PN) is a rare, autosomal dominant amyloidosis characterized primarily by progressive ascending sensorimotor neuropathy often associated with  autonomic involvement. hATTR-PN is caused by a mutation in the TTR gene leading to protein misfolding and amyloid accumulation in peripheral nerves and vital organs. The latest global prevalence estimates point to 10,000 cases worldwide, with an upper end of about 40,000. Tafamidis has been approved in over 40 countries for delaying neurologic disease progression in early-stage hATTR-PN. Multiple observational studies have examined clinical outcomes in hATTR-PN patients treated with tafamidis in the routine clinical setting. Integrative data analysis (IDA) is a technique for optimally constructing synthetic treatment and control cohorts from multiple independent studies, which allows meta-analysis of patient-level data. Herein, we provide a proof of concept for the application of IDA to real-world and natural history hATTR-PN data. IDA permits increased understanding of outcomes in tafamidis-treated and untreated persons with hATTR-PN by optimally pooling all available information. METHODS: Summary statistics corresponding to the Neuropathy Impairment Score-Lower Limb (NIS-LL) from five published studies were pooled, converted to change from baseline means and variances, and analyzed using IDA. IDA-based synthetic cohorts were generated by averaging across studies stratified on treatment versus control cohort. Trends in change from baseline in each study and the corresponding synthetic cohorts were plotted. Patient-level data were simulated from the synthetic cohort trends in a Monte Carlo simulation to highlight the ability to contrast synthetic cohort trends using the mixed model for repeated measures (MMRM). RESULTS: The average sample size among the five studies was 71 (37-128) patients. The average NIS-LL trends indicated that tafamidis-treated patients experienced slower progression in neuropathy compared to untreated patients. Synthetic cohort trends reflected the trends observed in the contributing studies, while simultaneously shrinking the width of corresponding confidence bands. Monte Carlo simulation results demonstrated precise recovery of the synthetic cohort and time-dependent simulated NIS-LL means by the MMRM. DISCUSSION: This proof of concept demonstrates the utility of IDA-based synthetic cohorts for increased precision in characterizing and testing hypotheses about treatment outcomes and prognosis in hATTR-PN. FUNDING: Pfizer. Plain language summary available for this article.

Biologic Disease-Modifying Antirheumatic Drugs in a National, Privately Insured Population: Utilization, Expenditures, and Price Trends.

BACKGROUND: Spending on biologic drugs is a significant driver of drug expenditures for payers in private health plans. Biologic disease-modifying antirheumatic drugs (DMARDs) are some of the most effective and costly treatments in a physician's arsenal. Understanding the total annual expenditure, the average cost per prescription, and the impact of cost-sharing is important for drug benefit managers. OBJECTIVE: To assess drug utilization, expenditures, out-of-pocket (OOP) cost, and price trends of biologic DMARDs in patients with rheumatoid arthritis (RA) in a large managed care organization. METHODS: We conducted a retrospective database analysis of pharmacy claims data from January 2004 to December 2013 using the Optum Clinformatics Data Mart database, which covers 13.3 million lives. Pharmacy claims for 40,373 patients with RA were identified during the study period. In all, 9 biologic DMARDs approved for the treatment of RA, including infliximab, etanercept, adalimumab, certoizumab, golimumab, tocilizumab, anakinra, abatacept, and rituximab, and 1 nonbiologic oral, small molecule-targeted synthetic drug, tofacitinib, were included in this study. Descriptive statistics were used to analyze the total annual number of prescriptions, the total annual expenditures, the average annual cost per drug (a proxy of drug price), and the average OOP cost (copay plus deductible and coinsurance). All measurements were also stratified by study drugs and by insurance type. RESULTS: Of the 40,373 patients with RA included in the study, approximately 76% were female (mean age, 55 years at diagnosis). Approximately 77% of the patients were white, and almost 48% lived in the South or Midwest region of the United States. Approximately 62% of patients had a point of service insurance plan. Expenditures on biologic DMARDs increased from $166 million in 2004 to $243 million in 2013, and the number of prescriptions and refills increased from 59,960 in 2004 to 105,295 in 2013. Prescriptions for biologic DMARDs increased more than 20% per patient from 2004 to 2013. The average cost per prescription remained relatively unchanged, at approximately $2300 per prescription, but the OOP expenditures increased from $36 (2.5%) per prescription to $128 (7%) during the study period. The OOP expenditures increased the most in HMO plans and in plans categorized as other (284% and 388%, respectively). CONCLUSIONS: Spending on biologic DMARDs has been primarily driven by an increase in prescribing rates, as the average amount reimbursed per prescription remained relatively unchanged over time, despite a regular annual increase to the average wholesale acquisition cost of 2% to 10%. The OOP burden for patients has increased, but this does not appear to have limited the use of biologic DMARDs. The entrance of new biologic and nonbiologic DMARDs into the market in the past few years is eroding the market share for several established drugs, and may lead to different results, warranting a study of new trends.