A review of moxidectin vs. other macrocyclic lactones for prevention of heartworm disease in dogs with an appraisal of two commercial formulations.

Macrocyclic lactones (MLs) are the only drug class currently licensed for heartworm disease prophylaxis. Macrocyclic lactones kill third- and fourth-stage larvae of Dirofilaria immitis, thus preventing the development of adult worms in dogs, which are responsible for heartworm disease, a potentially life-threatening condition. Despite considerable overlap in terms of endectocide spectrum, several important differences distinguish moxidectin from other MLs. Moxidectin has beneficial pharmacokinetic characteristics, such as a longer half-life and greater tissue distribution compared to ivermectin. Additionally, moxidectin has a greater margin of safety compared to ivermectin in dogs with ABCB1 (previously MDR1) gene-defect, which is commonly recognized in collies and other breeds. Multiple laboratory studies have shown that moxidectin is more effective than other commonly used heartworm preventives against resistant strains of D. immitis. This improved efficacy benefits individual dogs and helps reduce the risk of spreading resistant strains within the community. Despite the presence of proven resistant strains in the United States, non-compliance with preventive measures remains a major factor contributing to the diagnosis of heartworm disease in dogs. In retrospective analyses, the oral moxidectin combination product Simparica Trio® (sarolaner, moxidectin, and pyrantel) was associated with increased compliance, resulting in more time of protection compared to dogs receiving flea/tick and heartworm preventive products separately. Compliance with the extended-release moxidectin injectables ProHeart® 6 and ProHeart® 12 was higher than with monthly heartworm preventives, as they provide 6 months or a full year of protection with one single injection, respectively, and revenues remain in the veterinary clinics as injectable moxidectin cannot be sourced through online retailers.

Retrospective analyses of heartworm (Dirofilaria immitis) disease and ectoparasite preventive medication compliance in veterinary practices in the USA.

BACKGROUND: Compliance failure with administration of heartworm (HW) disease preventives has been reported as the main contributor to HW disease incidence in medicalized dogs. This study aimed to evaluate purchase compliance with different canine HW preventive products in the USA. METHODS: Anonymized transaction data from clinics throughout the USA served as the basis for two retrospective analyses. We first examined the monthly equivalent doses of HW preventive purchases from clinics that had implemented extended-release moxidectin injectables ProHeart® 6 (PH6) and/or ProHeart® 12 (PH12) compared to clinics that prescribed monthly HW preventatives (MHWP) only. In the second analysis, the purchase compliance in practices that dispensed only flea and tick (FT) and HW products separately but did not dispense combination products (dual-therapy practices) was compared to the purchase compliance with the combination product Simparica Trio® (sarolaner, moxidectin, and pyrantel chewable tablets), purchased in clinics having implemented combination therapy in their formulary (combination-therapy practices). In both analyses, the numbers of monthly doses dispensed annually per dog were calculated. RESULTS: Transaction data from 3,539,990 dogs in 4615 practices were included in the first analysis. In dogs administered PH12 or PH6, the numbers of monthly equivalent doses were 12 and 8.1, respectively. In both clinic types, the average annual number of MHWP doses totaled 7.3. In the second analysis, a total of 919 practices were identified as combination-therapy practices and 434 as dual-therapy-only practices. A total of 246,654 dogs (160,854 dogs in dual-therapy practices and 85,800 dogs in combination-therapy practices) were included in the calculation of the average annual number of monthly doses, which totaled 6.8 (HW preventive products) and 4.4 (FT products) in dual-therapy practices compared to 7.2 months for both FT and HW preventives with Simparica Trio® across both practice types. CONCLUSIONS: The injectable HW preventive PH12 is the only product that provides 12 months of heartworm disease prevention in a single veterinarian-administered injection. When choosing a monthly preventive, the combination therapy was associated with a greater purchase compliance compared with FT and HW products being dispensed separately.

A Chimeric Vaccine against Porcine Circovirus Type 2: Meta-Analysis of Comparative Clinical Trials.

This meta-analysis compared the efficacy of a chimeric vaccine against porcine circovirus type 2 (PCV2) containing the genotypes PCV2a+b (Fostera® Gold PCV MH [FOS-G]), with commonly used vaccines being derived from genotype PCV2a, considering the following parameters: average daily gain (ADG), mortality and market classification as full value and cull. Data from seven hitherto unpublished comparative US field trials with FOS-G (two experimental challenges and five natural environmental studies) were provided by the manufacturer. A complementary literature review revealed a Korean study, which was considered separately in meta-analysis. Competitors were Circumvent® PCV-M (CV) and Ingelvac Circoflex® + Ingelvac Mycoflex® (IC + IM) in the US, and Porcilis® (POR) in Republic of Korea. Heterogeneity between experimental and environmental challenge studies in the US was not significant, justifying a combined analysis. Over the entire feeding period, ADG (11 comparisons), mortality (12 comparisons) and market classification were not significantly different between FOS-G and its competitor in the US setting. In the Korean study, however, ADG was higher in pigs vaccinated with FOS-G compared to POR, whereas mortality was not significantly different.

Prevention and long-term outcomes of naturally occurring canine heartworm infection in primary care settings.

Background: This study had two objectives: first, to examine the association between the history of heartworm preventive purchase compliance and the risk of positive heartworm tests, and second to preliminarily investigate the long-term cardiac outcomes of heartworm disease in dogs that had undergone successful adulticidal therapy. Methods: A retrospective cohort study design was used for both analyses, using anonymous transaction data from Covetrus (retrospective analysis 1) and anonymized medical records from Banfield Pet Hospital (retrospective analysis 2), both including canine patients across the USA. The first analysis examined the relative risk (RR) of a positive heartworm test in dogs with lapses in heartworm preventive purchase history compared to dogs that had no history of a preventive purchase six to 24 months prior to the test. In the second analysis, a long-term evaluation of structured diagnostic codes pertaining to cardiac diseases and risk assessment of outcomes was performed in dogs that had previously been successfully treated for heartworm disease compared to dogs that never had a positive heartworm test. Results: 83,478 unique patients were included in the first analysis. Compared to 32,413 dogs with no history of a heartworm preventive purchase, 44,410 dogs with lapses in monthly preventive purchases had a reduced risk of testing positive for heartworm disease (RR = 0.36, p < 0.0001). Dogs (n = 6,655) with lapses in injectable heartworm preventive administration had a decreased risk of a positive test versus dogs with no preventive purchases (RR = 0.15, p < 0.0001), as well as versus dogs with lapses in monthly heartworm preventive purchases (RR = 0.28, p = 0.0024). In the second analysis, 6,138 patients treated for heartworm infection were found to have significantly (p < 0.001) elevated risks of right heart failure (RR = 3.59), left heart failure (RR = 1.83), or cardiomyopathy (RR = 2.79) compared to 4,022,752 patients that never had a positive heartworm test. Conclusion: This study highlights the importance of compliance with heartworm preventive guidelines, to reduce the risk of heartworm disease in dogs, which is not only a potentially life-threatening condition in the short-term but also associated with long-term negative cardiac outcomes.

Cost-utility analysis of increasing uptake of universal seasonal quadrivalent influenza vaccine (QIV) in children aged 6 months and older in Germany.

Seasonal influenza causes many cases and related deaths in Europe annually, despite ongoing vaccination programs for older adults and people at high-risk of complications. Children have the highest risk of infection and play a key role in disease transmission. Our cost-utility analysis, based on a dynamic transmission model, estimated the impact of increasing the current vaccination coverage with inactivated quadrivalent influenza vaccine in Germany to all (healthy and high-risk) children under 5 years of age (40% uptake), or under 18 years (40% uptake), or only high-risk children under 18 years (90% uptake). Eight influenza complications were modeled, hospitalization and death rates were based on age and risk status. All three vaccination strategies provided more health benefits than the existing vaccination situation, reducing influenza cases, complications, hospitalizations and deaths across the entire population. The strategy targeting all children under 5 years was highly cost-effective (€6/quality-adjusted life-year gained, payer perspective). The other strategies were cost saving from the payer and societal perspectives. The vaccination strategy targeting all children under 18 years was estimated to provide the most health benefits (preventing on average 1.66 million cases, 179,000 complications, 14,000 hospitalizations and 3,600 deaths due to influenza annually) and the most cost savings (annually €20.5 million and €731.3 million from payer and societal perspectives, respectively). Our analysis provides policy decision-makers with evidence supporting strategies to expand childhood influenza vaccination, to directly protect children, and indirectly all other unvaccinated age groups, in order to reduce the humanistic and economic burden on healthcare systems and society.

What is the context? Every winter, millions of people in Europe become ill due to influenza (flu), and some need to be hospitalized for complications that can sometimes lead to death.While mainly older adults and people with chronic illness are at higher risk of complications from influenza, children have the highest risk of infection and of transmitting the disease.Current vaccination policies in Europe, including Germany, target older adults and high-risk populations (pregnant women, children and other age groups with chronic diseases).What is new? This analysis simulates the effects of expanding current German vaccination programs in high-risk children to include healthy children, and of increasing vaccination coverage rates, for direct protection against infection, and to reduce the disease transmission in the rest of the population.We modeled three vaccination strategies: vaccinating 40% of all (healthy and high- risk) children under 5 years old;vaccinating 40% of all (healthy and high-risk) children under 18 years old;vaccinating 90% of high-risk children under 18 years old.What is the impact? All three strategies resulted in health gains, as more influenza cases, complications and deaths were prevented in all age groups of the population compared to the current situation.The strategies targeting both healthy and high-risk children provided the greatest health benefits. In particular, a vaccination policy targeting all children under 18 years old was predicted to provide the most health benefits as well as the highest cost savings: the increased costs of vaccination were more than offset by the savings in disease management costs as a result of having fewer influenza patients.Vaccinating healthy children against influenza is expected to significantly reduce the disease burden in the total population while saving costs, due to reduced transmission of the disease.

Do High Levels of Maternally Derived Antibodies Interfere with the Vaccination of Piglets against Porcine Circovirus Type 2? A Literature Review and Data Analysis.

Vaccination against porcine circovirus type 2 (PCV2) is commonly performed in piglets worldwide, and increasingly also in sows. We conducted a literature search and review to assess the potential interference of maternally derived antibodies (MDA) in piglets with vaccination against PCV2. The effectiveness of vaccination was compared to no vaccination in the presence of high levels of MDA (≥8 log2 IPMA titer), as reported in field studies. In total, 13 papers fulfilled the predefined inclusion criteria, allowing up to 24 comparisons per parameter. In the presence of high levels of MDA, vaccinated pigs had, on average, a 20 g/d higher mean daily weight gain and a 34% lower mortality compared to non-vaccinates. The maximum percentage of viremic pigs was reduced by 63% and the maximum viral load in serum was 0.72 log10 PCV2 DNA copies lower. Vaccination at 3 weeks of age was associated with the highest improvements in production parameters and reductions in viremia. Our findings suggest that the vaccination of piglets is effective with respect to production parameters and viremia even in the presence of high MDA, with an age of 3 weeks at vaccination being most beneficial.

Cost-effectiveness of the recombinant zoster vaccine in the German population aged ≥60 years old.

Each year, around 300,000 Herpes Zoster (HZ) cases are observed in the German population, resulting in costs over €182 million to society. The objective of this study was to estimate the potential public health and economic impact of the new Adjuvanted Recombinant Zoster Vaccine (RZV, Shingrix) in the German population ≥ 60 years of age (YOA) and to identify the optimal age of vaccination. We used a static, multi-cohort Markov model that followed a hypothetical cohort of 1 million people ≥ 60 YOA life-long after vaccination using German-specific inputs. Both costs and outcomes were discounted at 3%, the incremental cost-effectiveness ratio (ICER) was calculated based on the societal perspective. The coverage of RZV was set at 40% with a second-dose compliance of 70%. Vaccinating the population aged ≥ 60 YOA would result in 45,000 HZ cases avoided, 1,713 quality-adjusted life years (QALYs) gained at a total cost of approximately €63 million compared to 38,000 cases avoided, 1,545 QALYs gained at a total cost of approximately €68 million in the population ≥ 70 YOA. This would result in an ICER of approximately €37,000 and €44,000/QALY, for the age cohort ≥ 60 and ≥ 70 YOA, respectively. Scenario analyses demonstrated that vaccinating at age 60 or 65 YOA would show greater public health impact and would result in the lowest observed ICER compared to vaccinating at 70 YOA. In conclusion, starting vaccination with RZV in the German population ≥ 60 YOA would demonstrate the best value from a public health and economic standpoint.

Cost-Utility of Quadrivalent Versus Trivalent Influenza Vaccine in Germany, Using an Individual-Based Dynamic Transmission Model.

BACKGROUND: Seasonal influenza infection is primarily caused by circulation of two influenza A strain subtypes and strains from two B lineages that vary each year. Trivalent influenza vaccine (TIV) contains only one of the two B-lineage strains, resulting in mismatches between vaccine strains and the predominant circulating B lineage. Quadrivalent influenza vaccine (QIV) includes both B-lineage strains. The objective was to estimate the cost-utility of introducing QIV to replace TIV in Germany. METHODS: An individual-based dynamic transmission model (4Flu) using German data was used to provide realistic estimates of the impact of TIV and QIV on age-specific influenza infections. Cases were linked to health and economic outcomes to calculate the cost-utility of QIV versus TIV, from both a societal and payer perspective. Costs and effects were discounted at 3.0 and 1.5 % respectively, with 2014 as the base year. Univariate and probabilistic sensitivity analyses were conducted. RESULTS: Using QIV instead of TIV resulted in additional quality-adjusted life-years (QALYs) and cost savings from the societal perspective (i.e. it represents the dominant strategy) and an incremental cost-utility ratio (ICUR) of €14,461 per QALY from a healthcare payer perspective. In all univariate analyses, QIV remained cost-effective (ICUR <€50,000). In probabilistic sensitivity analyses, QIV was cost-effective in >98 and >99 % of the simulations from the societal and payer perspective, respectively. CONCLUSION: This analysis suggests that QIV in Germany would provide additional health gains while being cost-saving to society or costing €14,461 per QALY gained from the healthcare payer perspective, compared with TIV.

Cost-effectiveness of strong opioids focussing on the long-term effects of opioid-related fractures: a model approach.

Opioid analgesics are known to impact on the central nervous system (CNS). These CNS side effects, such as dizziness and confusion, have been shown to lead to an increased risk of falling with subsequent fractures in elderly patients being treated with opioids. The risk of experiencing fractures has been shown to be dependent on the substance administered. Therefore, a health economic model was developed to investigate the cost-effectiveness of the most commonly used strong opioids in Germany, focussing on opioid-related fractures. By means of a Markov model, the consequences of hip, spine and forearm fractures due to the prior administration of transdermal (TD) buprenorphine, TD fentanyl, oral oxycodone as well as oral morphine were assessed from the perspectives of the German statutory health insurance (SHI) and the German social security (GSS) system over a time horizon of 6 years. The most frequently prescribed strength/package-size combinations of these opioids were taken into consideration, including generics where available. The results of the present analysis predict that TD buprenorphine is dominant compared to TD fentanyl and oxycodone by showing better effects [life years gained/quality adjusted life years (QALY) gained] at lower cost. From the SHI perspective, the incremental cost-effectiveness ratio (ICER) compared to morphine is 6,801.61 per life year gained, and 7,766.11 per QALY gained. From the GSS perspective, the ICER is 2,496.77 per life year gained and 2,850.83 per QALY gained. The model is robust regarding probabilistic variations of all parameters in the sensitivity analyses. Focussing on fractures due to the prior administration of strong opioids, TD buprenorphine is less costly and more effective than TD fentanyl and oxycodone and represents a cost-effective treatment option versus morphine in patients with chronic pain from both the SHI and GSS perspective in Germany.

Patterns of dosage changes with transdermal buprenorphine and transdermal fentanyl for the treatment of noncancer and cancer pain: a retrospective data analysis in Germany.

BACKGROUND: Previous studies have suggested that buprenorphine may have a low association with tolerance development compared with other strong opioids. In a previous study by our group, mean cohort and intraindividual dosage increases over an entire course of treatment and on a per-day basis were significantly lower with transdermal (TD) buprenorphine than with TD fentanyl. However, no information concerning the relationship between qualitative and quantitative dose changes is available. OBJECTIVE: The aim of this study was to compare TD buprenorphine and TD fentanyl with respect to dosage increases, dosage stability, and the nature of dosage changes. METHODS: This retrospective analysis used data from the IMS Disease Analyzer-Mediplus database, which contains patient-related data documented by 400 medical practices in Germany. Data from patients with noncancer or cancer pain treated with TD buprenorphine or TD fentanyl for at least 3 months between May 2002 and April 2005 were analyzed. Daily dosages were directly determined from the prescribed patch strength, taking into account the possibility of multiple patches applied simultaneously. To determine dosage stability, patients were classified based on the type of dosage change (stable, increase, alternating, or decrease) of the prescribed dosages. From the prescribed daily dosages, mean percentage increases were calculated on a per-patient basis for the entire treatment period and per day, and these were assessed in relation to the type of dosage change. RESULTS: In total, 631 patients with noncancer pain and 605 patients with cancer pain were included in the analysis (782 women, 454 men; mean age, 76.3 years [range, 29-100 years]). Treatment indications included osteoarthritis, low back pain, osteoporosis (noncancer groups), and neoplasm (cancer groups). Patients had similar analgesic premedication requirements based on steps 1 to 3 of the World Health Organization analgesic ladder. Comedication requirements for breakthrough pain were also similar between the TD buprenorphine and TD fentanyl groups. The mean percentage increases per day were 0.10% (TD buprenorphine) and 0.25% (TD fentanyl) in the noncancer groups and 0.19% (TD buprenorphine) and 0.47% (TD fentanyl) in the cancer groups (both, P < 0.05). A significantly larger proportion of patients receiving TD buprenorphine had stable dosages over the entire treatment period compared with patients receiving TD fentanyl (noncancer groups: 56.9% vs 41.6%; cancer groups: 50.0% vs 26.2% [both, P < 0.05]). Compared with TD buprenorphine, the proportion of patients with alternating dosage changes was significantly greater in patients receiving TD fentanyl (noncancer groups: 22.7% vs 13.1%; cancer groups: 30.6% vs 11.8% [both, P < 0.05]). CONCLUSIONS: In this retrospective data analysis, compared with TD buprenorphine, the increase in mean daily dosage was significantly greater in patients treated with TD fentanyl. Also, compared with TD buprenorphine, alternating dosage changes were seen in a significantly greater proportion of patients receiving TD fentanyl. On the other hand, a significantly greater proportion of patients treated with TD buprenorphine had stable dosages over their entire treatment periods.

Oral fixed drug combination analgesic tramadol/paracetamol: benefits for patients and budgets.

Although pain can present in many different ways, acute, subacute and chronic pain are frequently used and helpful categories that cover a wide range of pain phenomena. This paper reviews five cost-minimization studies of tramadol/paracetamol compared with codeine/paracetamol, immediate-release tramadol and nonsteroidal anti-inflammatory drugs for the treatment of postsurgical pain, lower back pain and osteoarthritis. These conditions represent the main general indications for the combination analgesic. This economic modeling data is preceded by a discussion of each pain type, focusing on the published clinical literature of the efficacy of tramadol/paracetamol and relevant comparators. For the cost-minimization studies, each model employed a similar decision analytical framework, with data derived from clinical trials, Delphi panels and official price and tariff lists. Rollback analyses were used to calculate the cost of treatment per patient. The initial hypothesis in each study was that higher drug costs for tramadol/paracetamol would be offset by a reduction of costs associated with the treatment of side effects. In addition, a cost-utility model carried out among patients with moderate or severe back pain could also underline a benefit-adjusted outcome (quality of life) for patients treated with tramadol/paracetamol. Results of the published clinical literature and these recent economic analyses suggest that tramadol/paracetamol, by reducing the incidence of adverse events, provides benefits for both patients and budgets.