Zoledronic Acid: A Pharmacoeconomic Review of its Use in the Management of Bone Metastases

Zoledronic acid (Zometa(R)) is a third-generation nitrogen-containing parenteral bisphosphonate indicated for the treatment of bone metastases due to solid tumours or multiple myeloma and for hypercalcaemia of malignancy (HCM). In patients with advanced breast or prostate cancer, zoledronic acid 4 mg every 3-4 weeks for up to 15 months significantly reduced the proportion of patients with >=1 skeletal-related event (SRE), excluding HCM, compared with placebo. In patients with advanced breast cancer or multiple myeloma, the incidence of SREs was similar in patients treated with zoledronic acid 4 mg or pamidronic acid 90 mg every 3-4 weeks for up to 25 months but, in breast cancer patients, zoledronic acid reduced the risk of SREs, including HCM, by an additional 20% compared with pamidronic acid. In modelled cost-utility studies comparing direct costs based on efficacy and resource-use data from these and/or other trials, results have varied. In the most recent study performed from the perspective of the UK NHS and modelled over a 10-year treatment period in women with advanced breast cancer, intravenous zoledronic acid and oral ibandronic acid were dominant over no treatment. Intravenous zoledronic acid was the most cost effective, in terms of incremental costs per QALY gained, followed by oral ibandronic acid, intravenous pamidronic acid and intravenous ibandronic acid. Two other modelled analyses in patients with advanced breast cancer, also conducted from the perspective of the NHS, evaluated the cost utility of three bisphosphonate therapies in patients receiving hormonal therapy or intravenous chemotherapy. Analyses were modelled over 14.3 months (i.e. expected survival) and assumptions varied markedly from results in clinical breast cancer trials. Also, efficacy assumptions for zoledronic acid were not based on clinical trials with the drug. The results of these analyses suggest that oral ibandronic acid is more cost effective than intravenous zoledronic acid and intravenous pamidronic acid in terms of incremental cost per QALY gained. In a global, 15-month modelled cost-effectiveness analysis of patients with advanced prostate cancer, conducted from a third-party perspective, the incremental cost per QALY gained for zoledronic acid versus no treatment was $US159_200 (year 2000 value), which is about 3-fold greater than commonly accepted thresholds for cost effectiveness. In conclusion, a recent modelled economic analysis suggests that intravenous zoledronic acid 4 mg is dominant relative to no treatment in the management of bone metastases in patients with advanced breast cancer. In contrast, in patients with advanced prostate cancer, the incremental cost per QALY gained for zoledronic acid 4 mg versus no treatment was predicted to be higher than commonly accepted thresholds. Compared with other bisphosphonates in the setting of advanced breast cancer, intravenous zoledronic acid was more cost effective than oral or intravenous ibandronic acid and intravenous pamidronic acid in one study, but less cost effective than oral ibandronic acid in another. Further efficacy and economic data comparing intravenous zoledronic acid with oral ibandronic acid are needed. Meanwhile, zoledronic acid appears to be the most cost effective intravenous bisphosphonate for the management of bone metastases in patients with advanced breast cancer and possibly in patients with different types of advanced solid tumours.Adis-Drug-Evaluations, Bone-cancer, Cancer, Cost-effectiveness, Cost-utility, Zoledronic-acid

Fondaparinux: A Pharmacoeconomic Review of its Use in the Management of Non-ST-Segment Elevation Acute Coronary Syndrome

Fondaparinux (Arixtra) is an anticoagulant that selectively inhibits activated factor X, thereby interrupting the blood coagulation cascade. In OASIS-5, a large pivotal trial in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), subcutaneous fondaparinux 2.5 mg once daily was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (both agents were administered over a mean of about 5 days in combination with antiplatelet therapy) in reducing death or ischaemic events at 9 days, and the efficacy was maintained for up to 6 months (study end). However, fondaparinux was associated with a significantly lower rate of bleeding than enoxaparin in the first 9 days, and at 3 and 6 months. This lower rate of bleeding led to lower long-term mortality and morbidity with fondaparinux than with enoxaparin. In modelled cost-utility analyses conducted from a healthcare payer perspective in Spain, France and the US with a lifetime horizon, fondaparinux once daily was predicted to be cost effective relative to enoxaparin twice daily with regard to the incremental cost per QALY gained. In Spain and the US, fondaparinux dominated enoxaparin (i.e. was less costly and more effective) and, in the French analysis, the incremental cost per QALY gained with fondaparinux versus enoxaparin was well within recommended thresholds. Results of short-term (6-month) cost analyses in the US and France also favoured fondaparinux over enoxaparin. Sensitivity analyses demonstrated that base-case conclusions were robust over a range of parameter estimates and assumptions, including plausible variations in baseline risk of a cardiac event or baseline risk of bleeding. In conclusion, in patients with NSTE-ACS receiving antiplatelet therapy, fondaparinux was cost effective relative to enoxaparin in cost-utility analyses in Europe and the US. This cost advantage primarily reflects the lower rate of bleeding with fondaparinux than with enoxaparin and the lower rate of mortality and morbidity over the long term.Acute-coronary-syndromes, treatment, Adis-Drug-Evaluations, Cost-effectiveness, Cost-utility, Enoxaparin-sodium, therapeutic use, Fondaparinux-sodium, therapeutic use, Myocardial-infarction, treatment

Trastuzumab: A Pharmacoeconomic Review of its Use in Early Breast Cancer

Trastuzumab (Herceptin(R)) is a monoclonal antibody approved for the treatment of breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2). Well designed clinical trials in women with early breast cancer have demonstrated that 1 years' therapy with adjuvant intravenous trastuzumab (a loading dose followed by 6 mg/kg every 3 weeks or 2 mg/kg weekly) significantly improves disease-free survival and overall survival compared with observation (subsequent to chemotherapy) or chemotherapy alone in women with HER2-positive disease. In the HERA trial, disease-free survival was estimated to improve by 6.3% at 3 years in the trastuzumab group compared with the observation group. Trastuzumab is generally well tolerated. The most common adverse events are infusion-related symptoms, such as fever and chills, which usually occur with administration of the first dose. Cardiotoxicity occurs in a small proportion of patients receiving trastuzumab, particularly when coadministered with anthracyclines, and cardiac assessment is recommended for all patients at baseline and at 3-monthly intervals. In modelled cost-effectiveness analyses based on data from clinical trials in patients with HER2-positive early breast cancer, adjuvant trastuzumab was predicted to be cost effective from a healthcare payer or societal perspective in several countries. Incremental costs per QALY or life-year gained with trastuzumab administered subsequent to or concurrent with chemotherapy compared with chemotherapy alone were consistently within accepted local thresholds for cost effectiveness. Sensitivity analyses demonstrated that these results remained generally robust to plausible changes in key model assumptions. In conclusion, in patients with HER2-positive early breast cancer, the addition of adjuvant trastuzumab is clinically effective in improving disease-free survival. Available pharmacoeconomic data from several countries, despite some inherent limitations, support the use of adjuvant trastuzumab for 1 year as a cost-effective treatment relative to chemotherapy alone in this patient population.Adis-Drug-Evaluations, Cost-effectiveness, Early-breast-cancer, Economic-implications, Trastuzumab

Poractant alfa in respiratory distress syndrome in preterm infants: a guide to its use

<div>Compliance with ethical standards</div><div><br></div><div><i>Funding:</i> The preparation of this review was not supported by any external funding.</div><div><br></div><div><i>Conflicts of interest:</i> K. McKeage and K.A. Lyseng-Williamson are employees of Adis/Springer, are responsible for the article content and declare no conflicts of interest.</div><div> </div><div>Additional information about this Adis Drug Review can be found <a href="http://www.springer.com/gp/adis/products-services/adis-journals-newsletters/adis-drug-reviews"><b>here</b></a>.</div><div><br></div><div>Abstract</div><div><br></div><div>Poractant alfa (Curosurf®) is a natural, porcine-derived surfactant that is well established as an effective and generally well-tolerated agent in the treatment of respiratory distress syndrome (RDS) in preterm infants. The efficacy of poractant alfa in RDS is better than that of early-generation synthetic surfactants, and limited data are available regarding its efficacy versus new-generation synthetic agents. Poractant alfa 200 mg/kg is more effective than poractant alfa 100 mg/kg or bovine-derived beractant 100 mg/kg. Techniques for administering poractant alfa include via an endotracheal tube or less invasive techniques [e.g. less invasive surfactant administration (LISA)] performed during non-invasive ventilation of spontaneously breathing infants via nasal continuous positive airway pressure (CPAP). Administration of poractant alfa 200 mg/kg in early rescue [i.e. fraction of inspired oxygen (FiO2) ≥ 0.3] via LISA is associated with increased successful management on continuous positive airway pressure, as well as reductions in the incidence of bronchopulmonary dysplasia (BPD) and death/BPD. Access to the full article can be found <b><a href="https://link.springer.com/article/10.1007/s40267-017-0437-3">here</a>.</b></div><div><br></div><div>© Springer International Publishing AG, part of Springer Nature 2017</div

Triptorelin 3- and 6-month sustained-release formulations in locally advanced or metastatic prostate cancer: a profile of their use in the EU

<div><i>Funding</i>: The preparation of this review was not supported by any external funding.</div><div><i><br></i></div><div><i>Conflicts of interest</i>: K. McKeage and K.A. Lyseng-Williamson are employees of Adis-Springer, are responsible for the article content and declare no conflicts of interest.</div><div><br></div><div>Further information about this Adis Drug Q&A can be found <b><a href="http://www.springer.com/gp/adis/products-services/adis-journals-newsletters/adis-drug-reviews">here</a>.</b></div><div><br></div><div>Abstract</div><div><br></div><div>Triptorelin [available in 1-, 3- and 6-month intramuscular sustained-release (SR) formulations] is a gonadotropin-releasing hormone (GnRH) agonist that effectively achieves and maintains castrate serum testosterone levels and is generally well tolerated in men with locally advanced or metastatic prostate cancer. The availability of the triptorelin 3- and 6-month SR formulations allows flexibility of treatment schedules for the patient and physician. The triptorelin 6-month SR formulation may improve convenience and patient’s potential adherence, health-related quality of life and resource use relative to GnRH agonists that require more frequent administration. This review provides a summary of the clinical evidence regarding the use of the 3- and 6-month SR formulations of triptorelin in the treatment of locally advanced and metastatic prostate cancer in the EU.</div><div> Access to the full article can be found <b><a href="https://link.springer.com/article/10.1007/s40267-017-0413-y">here</a>.</b></div><div><br></div><div>© Springer International Publishing AG, part of Springer Nature 2017</div><div><br></div

Linaclotide in constipation-predominant irritable bowel syndrome and chronic idiopathic constipation: a profile of its use in the USA

<div>Compliance with Ethical Standards</div><div><br></div><div><i>Funding:</i> The preparation of this review was not supported by any external funding.</div><div><br></div><div><i>Conflicts of interest:</i> Kate McKeage is a contracted employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest</div><div><br></div><div>Additional information about this Adis Drug Review can be found <b><a href="http://www.springer.com/gp/adis/products-services/adis-journals-newsletters/adis-drug-reviews">here</a>.</b></div><div><br></div><div>Abstract</div><div><br></div><div>Linaclotide (Linzess) is a synthetic guanylate cyclase C agonist that acts locally in the gastrointestinal tract to increase intestinal fluid levels, increase colonic transit, and reduce peripheral pain. In adults with constipation-predominant irritable bowel syndrome (IBS-C) or chronic idiopathic constipation (CIC), once-daily oral linaclotide 290 lg (IBS-C), or 145 or 72 lg (CIC), significantly improved stool frequency and consistency, abdominal pain and bloating, and health-related quality-oflife. Linaclotide is generally well tolerated and, consistent with its therapeutic action, diarrhea is the most common adverse event. Access to the full article can be found <b><a href="https://link.springer.com/article/10.1007/s40267-017-0448-0">here</a>.</b></div><div><br></div><div>© Springer International Publishing AG, part of Springer Nature 2017</div

Deflazacort in Duchenne muscular dystrophy: a profile of its use in the USA

<div>Compliance with ethical standards</div><div><br></div><div><i>Funding:</i> The preparation of this review was not supported by any external funding.</div><div><br></div><div><i>Conflicts of interest:</i> K. McKeage and K.A. Lyseng-Williamson are employees of Adis/Springer, are responsible for the article content and declare no conflicts of interest</div><div><br></div><div>Additional information about this Adis Drug Review can be found <b><a href="http://www.springer.com/gp/adis/products-services/adis-journals-newsletters/adis-drug-reviews">here</a>.</b></div><div><br></div><div>Abstract</div><div><br></div><div>Deflazacort (Emflaza™) is a derivative of prednisolone with immunomodulatory and anti-inflammatory properties. Overall, in the treatment of boys with Duchenne muscular dystrophy (DMD), deflazacort is as effective as prednisone, but may be better tolerated. In a randomized, double-blind, phase 3 trial in boys with DMD, deflazacort and prednisone both preserved muscle strength more effectively than placebo after 12 weeks of treatment, with improvements being maintained until study end at week 52. Both active treatments were also associated with improved motor function. In the real-word setting, treatment with corticosteroids for ≥ 1 year significantly delayed disease progression relative to no or < 1 month of corticosteroid treatment, with deflazacort showing some benefits over prednisone/prednisolone. Body weight gain-related events were less frequent with deflazacort than with prednisone, but stunted growth and the development of non-serious cataracts were more frequent. Access to the full article can be found <b><a href="https://link.springer.com/article/10.1007/s40267-017-0466-y">here</a>.</b></div><div><br></div><div>© Springer International Publishing AG, part of Springer Nature 2017 </div

Decitabine in newly diagnosed acute myeloid leukaemia: a profile of its use in the EU

<div>Compliance with ethical standards</div><div><br></div><div><i>Funding</i>: The preparation of this review was not supported by any external funding.</div><div><br></div><div><i>Conflicts of interest: </i>K. McKeage and K.A. Lyseng-Williamson are employees of Adis/Springer, are responsible for the article content and declare no conflicts of interest.</div><div><br></div><div>Additional information about this Adis Review Q&A can be found <b><a href="http://www.springer.com/gp/adis/products-services/adis-journals-newsletters/adis-drug-reviews">here</a>.</b></div><div><br></div><div>Abstract</div><div><br></div><div>Decitabine (Dacogen), a deoxynucleoside analogue of cytidine that selectively inhibits DNA methyltransferases, provides beneficial effects in adults with newly diagnosed acute myeloid leukaemia (AML) not eligible for standard induction chemotherapy. In DACO- 016, the registrational phase 3 clinical trial in this patient population, intravenous decitabine provided a clinically meaningful improvement in median overall survival (OS) relative to treatment choice (cytarabine or best supportive care) of 2 months (7.7 vs 5.0 months), as well as signifi- cant improvements in other efficacy outcomes. After a further year of follow-up, the difference in OS between treatment groups significantly favoured decitabine over treatment choice. Decitabine was generally well tolerated with a similar safety profile to that of low-dose cytarabine and low rates of early mortality. Consistent with the clinical presentation of AML, the most frequently observed adverse events were related to myelosuppression. Realworld studies support the effectiveness and tolerability profiles of decitabine in this indication. Access to the full article can be found <b><a href="https://link.springer.com/article/10.1007/s40267-017-0445-3">here</a>.</b></div><div><br></div><div>© Springer International Publishing AG, part of Springer Nature 2017</div