Patient-level indirect treatment comparison of lanadelumab versus pdC1-INH i.v. in hereditary angioedema patients: PATCH study.

BACKGROUND: Hereditary angioedema (HAE) is an autosomal dominant inherited disease in which patients suffer from local attacks primarily affecting skin and gastrointestinal tract, and sometimes even the upper respiratory tract leading to asphyxiation. Since head-to-head trials between authorized treatments are lacking, this study compares efficacy and safety of lanadelumab and intravenous plasma-derived C1-esterase inhibitor (pdC1-INH i.v.) in HAE patients on long-term prophylaxis by means of an indirect treatment comparison. METHODS: Efficacy and safety of lanadelumab against pdC1-INH i.v. were analyzed in a fully prespecified indirect comparison based on individual patient data (n = 231) from the HELP and CHANGE clinical trials. Primary and secondary efficacy endpoints were compared using a generalized linear model for count data. Confounding variables were identified a priori via systematic literature research and validated by clinical experts. Adjustment of confounders was implemented using a conditional regression model. RESULTS: Lanadelumab showed a statistically significant improvement in reduction of HAE attack rates compared to pdC1-INH i.v. across multiple endpoints: Monthly attack rate of patients treated with lanadelumab was less than half compared to pdC1-INH i.v. (Rate ratio: 0.486; 95% CI: 0.253, 0.932). Monthly rate of laryngeal attacks was found to be five times lower for lanadelumab (Rate ratio: 0.2; 95% CI: 0.044, 0.915) and monthly rate of acute treated HAE attacks among lanadelumab patients was about one third of the attack rate of pdC1-INH i.v. patients (Rate ratio: 0.366; 95% CI: 0.185, 0.727). CONCLUSION: This study contributes to current knowledge in the treatment of HAE by indicating a statistically significant reduction of HAE attacks under lanadelumab compared to pdC1-INH i.v.

Epidemiology, characteristics and treatment of patients with relapsing remitting multiple sclerosis and incidence of high disease activity: Real world evidence based on German claims data.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory, immune mediated disease of the central nervous system, with Relapsing Remitting MS (RRMS) being the most common type. Within the last years, the status of high disease activity (HDA) has become increasingly important for clinical decisions. Nevertheless, little is known about the incidence, the characteristics, and the current treatment of patients with RRMS and HDA in Germany. Therefore, this study aims to estimate the incidence of HDA in a German RRMS patient population, to characterize this population and to describe current drug treatment routines and further healthcare utilization of these patients. METHODS: A claims data analyses has been conducted, using a sample of the InGef Research Database that comprises data of approximately four million insured persons from around 70 German statutory health insurances (SHI). The study was conducted in a retrospective cohort design, including the years 2012-2016. Identification of RRMS population based on ICD-10 code (ICD-10-GM: G35.1). For identification of HDA, criteria from other studies as well as expert opinions have been used. Information on incidence, characteristics and current treatment of patients with RRMS and HDA was considered. RESULTS: The overall HDA incidence within the RRMS population was 8.5% for 2016. It was highest for the age group of 0-19 years (29.4% women, 33.3% men) and lowest for the age group of ≥ 50 years (4.3% women, 5.6% men). Mean age of patients with RRMS and incident HDA was 38.4 years (SD: 11.8) and women accounted for 67.8%. Analyses of drug utilization showed that 82.4% received at least one disease-modifying drug (DMD) in 2016. A percentage of 49.8% of patients received drugs for relapse therapy. A share of 55% of RRMS patients with HDA had at least one hospitalization with a mean length of stay of 13.9 days (SD: 18.3 days) in 2016. The average number of outpatient physician contacts was 28.1 (SD: 14.0). CONCLUSIONS: This study based on representative Germany-wide claims data from the SHI showed a high incidence of HDA especially within the young RRMS population. Future research should consider HDA as an important criterion for the quality of care for MS patients.

Increasing Divergence in Drug Prices Between the United States and Germany After Implementation of Comparative Effectiveness Analysis and Collective Price Negotiations.

BACKGROUND: Payers and purchasers in the United States seek to moderate drug prices and align them with the incremental clinical benefit offered by individual medications; some policymakers have proposed linking U.S. prices to an index of prices paid in other nations. The German health care system resembles that of the United States in featuring multiple private payers but differs in featuring a highly coordinated process of comparative clinical assessment and price negotiations for drugs. OBJECTIVES: To (a) measure trends in prices paid for physician-administered drugs in Germany before and after the mandate for comparative effectiveness assessment and price negotiations in 2011 and (b) compare them with price trends for the same drugs in the United States. METHODS: This study observed trends in the prices paid for 80 physician-administered drugs, which account for approximately half of Medicare Part B drug spending. Quarterly data covering 2004-2018 were obtained for Germany from the Lauer-Taxe database, which contains net prices paid by all German payers. U.S. data were obtained from the Centers for Medicare & Medicaid Services, which publishes net prices paid by private U.S. payers and the Medicare Part B program. These data contain the net prices actually paid after accounting for all discounts and rebates, not merely the manufacturer's list price. Statistical analyses were conducted with multivariable difference-in-differences regression methods. RESULTS: Before implementation in Germany of comparative effectiveness analysis and collective price negotiations, net U.S. prices for physician-administered drugs averaged 29.2% higher (95% CI = 26.6%-31.7) than those in Germany. After implementation of comparative effectiveness assessments and price negotiations in 2011, the divergence between U.S. and German prices increased another 28.9% (95% CI = 23.7%-34.3%). CONCLUSIONS: Commercial health insurers and Medicare pay significantly higher net prices for physician-administered drugs than do insurers in Germany, with the divergence growing after the mandate in Germany that new drugs be subject to comparative effectiveness assessment and collective price negotiations. The experience of Germany may be of special value for the current U.S. debate over pharmaceutical pricing reform, given the demographic, economic, and health system similarities between the 2 nations. DISCLOSURES: This study was supported by the Commonwealth Fund, New York. The sponsor had no role in the study design, conduct, interpretation, or writing up of results. Whaley reports a grant from the National Institute on Aging, unrelated to this work. The other authors have no potential conflicts of interest to report.