Cost-effectiveness analysis of recombinant human follicle-stimulating hormone alfa(r-hFSH) and urinary highly purified menopausal gonadotropin (hMG) based on data from a large German registry.

This was a retrospective real-world evidence analysis of the costs per live birth for reference recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG-HP), based on data from a German in vitro fertilization registry (RecDate). Pregnancy and live birth rates from the RecDate real-world evidence study over three complete assisted reproductive technology (ART) cycles using the same gonadotropin drug were used as clinical inputs. Costs related to ART treatment and to drugs were obtained from public sources. Treatment with r-hFSH-alfa resulted in higher adjusted cumulative live birth rates versus hMG-HP after one (25.3% vs. 22.3%), two (30.9% vs. 27.5%), and three (31.9% vs. 28.6%) ART cycles. Costs per live birth were lower with r-hFSH-alfa versus hMG-HP after one (€17,938 vs. €20,054), two (€18,251 vs. €20,437), and three (€18,473 vs. €20,680) ART cycles. r-hFSH-alfa was found to be a cost-effective strategy compared with hMG-HP over three cycles.

Originator recombinant human follitropin alfa versus recombinant human follitropin alfa biosimilars in Spain: A cost-effectiveness analysis of assisted reproductive technology related to fresh embryo transfers.

This study compared the cost per live birth and cost-effectiveness of the originator recombinant human follicle-stimulating hormone follitropin alfa (r-hFSH-alfa) and r-hFSH-alfa biosimilars for ovarian stimulation prior to assisted reproductive technology treatment in Spain. A decision tree model was developed, comprising pregnancy and live birth for one treatment cycle with fresh embryo transfer. Clinical inputs were based on a recent meta-analysis by Chua et al. [4]. Cost inputs were extracted from publicly available Spanish sources. The costs per live birth were lower with originator r-hFSH-alfa (€18,138) versus r-hFSH-alfa biosimilars (€20,377). The incremental cost-effectiveness ratio was €7208 for originator r-hFSH-alfa versus biosimilars. Drug acquisition costs for originator r-hFSH-alfa represented 10.5% of total costs in the base case analysis, and 6.2% in a treatment cycle resulting in live birth with one fresh embryo transfer. Results from the sensitivity analyses confirmed the robustness of the findings.

A cost-effectiveness evaluation of the originator follitropin alpha compared to the biosimilars for assisted reproduction in Germany.

Background and objectives: Demand for assisted reproduction technology (ART) in Germany is high, with 100,844 treatment cycles during 2016. Many ART procedures involve ovarian stimulation with follicle stimulating hormone (FSH). Recently, biosimilar FSH products have become available. The objective of this study was to evaluate the cost-effectiveness of the recombinant FSH Gonal-f® (Originator) in comparison to biosimilar follitropin alfa, Bemfola® (Biosimilar 1) and Ovaleap® (Biosimilar 2), from a German payer perspective in terms of cost per live birth. Methods: A decision tree model was developed, based on one cycle of assisted reproduction, to compare the original product to biosimilars. Clinical inputs, including live birth rates and adverse event rates were obtained from published randomized trials. Cost inputs were obtained from publicly available German sources. Clinical inputs, model structure and methodology were based on previous publications and validated by a clinical expert. Results: Results indicated that the live birth rate is higher for the Originator compared to Biosimilar 1 (40.7% vs 32.1% respectively), and Biosimilar 2 (32.2% vs 26.8%). The average cost per live birth for women treated with the Originator was estimated to be lower than those who were treated with biosimilars: Originator vs Biosimilar 1 (€10,510 vs €12,192), Originator vs Biosimilar 2 (€12,590 vs €13,606). The analysis also found that the Originator is associated with an incremental cost-effectiveness of €4,168 and €7,540 per additional live birth versus Biosimilar 1 and Biosimilar 2 respectively. Sensitivity analysis indicated probabilities of pregnancy, embryo transfer and live birth, were key drivers of model costs. Scenario analysis confirmed the robustness of the model outcomes. Conclusion: This study suggests that treatment with the Originator could result in a lower cost per live birth in comparison to biosimilars. Further analysis using real-world data, when available, is recommended to validate the results of the present study.

MAGE-A3 is a frequent tumor antigen of metastasized melanoma.

MAGE-3 or MAGE-A3 is one of the best-characterized tumor antigens. Due to its tumor-restricted expression pattern and its recognition by both cytotoxic and helper T cells it constitutes a promising tumor antigen for anticancer immunotherapy, notably of malignant melanoma. Surprisingly, however, only very limited information is available on the frequency and consistency of its expression in metastatic melanoma lesions. We have now investigated the presence of MAGE-A3 mRNA in 316 tumor samples from 147 melanoma patients by RT-PCR. MAGE-A3 mRNA was detectable in 62% of metastases, and expression did not depend on the site of the metastases (skin, lymph node, and internal organs), age, sex, or duration of disease. Southern blot hybridization of the PCR product enhanced sensitivity of detection, and 26% more samples (13/50 samples tested) scored positive, indicating an even higher MAGE-A3 mRNA frequency than determined by simple ethidium bromide gel analysis. In 62 patients, we were able to investigate MAGE-A3 expression in several metastases from the same patient, and unexpectedly, both MAGE-A3-positive and MAGE-A3-negative metastases were found in 32% of these patients (20 of 62). Immunohistochemistry (using mAb 57B) demonstrated that the expression pattern was usually also heterogeneous with positively and negatively stained tumor cells within one metastasis. However, most (90%) of the metastases (47/52) gave a partially positive signal. Taken together, MAGE-A3 is a common and frequent tumor antigen in metastasized melanoma, but its expression is often heterogeneous.

Age-related differences in response to peginterferon alfa-2a/ribavirin in patients with chronic hepatitis C infection.

AIM: To evaluate the safety and efficacy of pegylated interferon alfa-2a and ribavirin therapy in elderly patients with chronic hepatitis C infection. METHODS: Patients characteristics, treatment results and safety profiles of 4859 patients with hepatitis c virus (HCV) infection receiving treatment with pegylated interferon alfa-2a and ribavirin were retrieved from a large ongoing German multicentre non-interventional study. Recommended treatment duration was 24 wk for GT 2 and GT 3 infection and 48 wk for GT 1 and GT 4 infection. Patients were stratified according to age (< 60 years vs ≥ 60 years). Because of limited numbers of liver biopsies for further assessment of liver fibrosis APRI (aspartate aminotransferase - platelet ratio index) was performed using pre-treatment laboratory data. RESULTS: Out of 4859 treated HCV patients 301 (6.2%) were ≥ 60 years. There were more women (55.8% vs 34.2%, P < 0.001) and predominantly GT 1 (81.4% vs 57.3%, P < 0.001) infected patients in the group of patients aged ≥ 60 years and they presented more frequently with metabolic (17.6% vs 4.5%, P < 0.001) and cardiovascular comorbidities (32.6% vs 6.7%, P < 0.001) and significant fibrosis and cirrhosis (F3/4 31.1% vs 14.0%, P = 0.0003). Frequency of dose reduction and treatment discontinuation were significantly higher in elderly patients (30.9% vs 13.7%, P < 0.001 and 47.8% vs 30.8%, P < 0.001). Main reason for treatment discontinuation was "virological non-response" (26.6% vs 13.6%). Sustained virological response (SVR) rates showed an age related difference in patients with genotype 1 (23.7% vs 43.7%, P < 0.001) but not in genotype 2/3 infections (57.7% vs 64.6%, P = 0.341). By multivariate analysis, age and stage of liver disease were independent factors of SVR. CONCLUSION: Elderly HCV patients differ in clinical characteristics and treatment outcome from younger patients and demand special attention from their practitioner.

The economic burden of advanced Parkinson's disease: an analysis of a UK patient dataset.

BACKGROUND: To evaluate the cost burden of patients with advanced Parkinson's disease (PD) according to the waking hours per day spent in OFF state. An analysis of resource use comprising medical services, professional care and informal care data from an observational, cross-sectional study was conducted. METHODS: A total of 60 physicians comprising 40 neurologists and 20 geriatricians across the UK participating in the Adelphi PD Disease Specific Programme took part. There were 302 PD patients at H&Y stages 3-5. Patients were characterised according to the percentage of time per day spent in OFF state (<25%, 26-50%, 51-75%, >75%). RESULTS: Average 12-monthly total costs increased according to the time spent in OFF state from £25,630 in patients spending less than 25% of their waking hours in OFF to £62,147 for patients spending more than 75% of their time in OFF. Overall, 7% of costs were attributed to direct medical care, while 93% were split between direct non-medical professional care (50%) and indirect informal care (43%). LIMITATIONS: Low patient numbers in the more advanced disease stages of PD led to very little or no data to directly inform some of the severe health states of the analysis. Data gaps were filled in with data derived from a regression analysis which may affect the robustness of the analysis. CONCLUSION: This study illustrates the increasing costs of advancing PD, in particular related to the time spent in OFF state, and identifies that the foremost cost burden is associated with the care needs of the patient rather than medical services.

A cost-effectiveness analysis of levodopa/carbidopa intestinal gel compared to standard care in late stage Parkinson's disease in the UK.

OBJECTIVE: Evaluation of cost-effectiveness of levodopa/carbidopa intestinal gel (LCIG), compared to standard care (SC) in patients with advanced Parkinson's disease (aPD) in the UK. DESIGN: Markov model to quantify costs and outcomes associated with LCIG versus SC in aPD patients at Hoehn and Yahr (H&Y) stages 3, 4 or 5 experiencing >50% OFF time per day. Time horizon was lifetime, LCIG treatment was assumed to last maximal 5 years after which patients revert to SC. Model comprised 12 aPD health states according to H&Y status and daily time spent in OFF state. Cost analyses are reported from a UK NHS and Personal Social Services perspective. Uncertainties were assessed through one-way sensitivity analyses. COMPARATORS: LCIG, providing patients with continuous dopaminergic stimulation to maximise functional ON time during the day and SC, defined as medically determined best available oral medication. MAIN OUTCOME MEASURES: Cost-effectiveness, based on quality adjusted life years gained, presented as an incremental cost-effectiveness ratio. RESULTS: Lifetime analysis yields an incremental cost per QALY of £36,024 for LCIG compared to SC (incremental cost £39,644, QALY gain 1.1). Results were sensitive to time on treatment, health state on treatment initiation, and estimates of long term benefit (OWSA results from £32,127 to £66,421 per QALY). Findings must be considered in the context of the study limitations which were mainly due to data availability constraints. CONCLUSIONS: LCIG is an effective treatment, reducing OFF time and improving quality of life in advanced PD. It provides value for money in levodopa-responsive aPD patients with severe motor fluctuations when no other treatment options are effective or suitable. Given LCIG is an orphan drug, it is reasonable to suggest that it may be considered cost-effective in the UK setting. However, further research is needed to complete current data gaps and increase robustness of the model.