Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy.

Background: Abemaciclib was recently approved by the European Medicines Agency in combination with adjuvant endocrine therapy (ET) for adult patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive early breast cancer (EBC) at high risk of recurrence. Objective: To evaluate the cost-effectiveness of abemaciclib plus ET vs. ET alone in patients with HR+, HER2-, node-positive EBC at high risk of disease recurrence, from the Italian healthcare system perspective. Methods: A cohort state transition model was developed with five states: invasive disease-free survival (IDFS), nonmetastatic recurrence, remission, metastatic recurrence, and death. The analysis had a time horizon of 30 years. Individual patient-level data from the monarchE trial (NCT03155997) were used to generate IDFS estimates. Resource use included drug acquisition/administration, best supportive care, terminal care, adverse events, hospitalization, post-progression therapy, and associated resource use in the metastatic disease health state. Health state utilities were derived from monarchE patient-level data and other sources, applying Italian tariffs where feasible. Results: The estimated total discounted costs (€39,249 vs. €16,806; difference: €22,443) and quality-adjusted life years (QALYs) (11.49 vs. 10.50; difference: 0.99) were higher for abemaciclib plus ET compared with ET alone. The incremental cost-effectiveness ratio was €22,651 per QALY gained. The likelihood of abemaciclib plus ET being cost-effective vs. ET alone was 99% at a willingness-to-pay threshold of €30,000 per QALY gained. Conclusion: Abemaciclib plus ET is a cost-effective treatment option vs. ET alone for those with HR+, HER2- node-positive EBC at high risk of recurrence in Italy.

Systematic literature review and network Meta-analysis of sulodexide and other drugs in chronic venous disease.

OBJECTIVE: To assess the clinical efficacy of sulodexide, including a comparison with venoactive drugs (VAD) (micronized purified flavonoid fraction, MPFF; hydroxy-ethyl-rutosides, HR; calcium dobesilate;Ruscus extract combined with hesperidin methyl chalcone and vitamin C, Ruscus+HMC+VitC; horse chestnut seed extract, HCSE) and pentoxifylline in patients with chronic venous disease. METHODS: We performed a literature search in MEDLINE, Embase, and Cochrane Library for randomized controlled trials (RCTs) and observational studies. Proportion of patients with complete venous ulcer healing was the primary outcome and lower leg volume, foot volume, ankle circumference and symptoms were the secondary outcomes. Bayesian network meta-analysis (NMA) was perfomed with random effects models using only RCTs. A meta-analysis of observational studies was performed for sulodexide because no RCT could be included in NMA for symptoms or signs. RESULTS: Forty-five RCTs and eighteen observational studies were identified. Sulodexide was included only in a single NMA for the proportion of patients with complete ulcer healing and it showed to have the highest probability of being the best treatment (48%) compared with pentoxifylline (37%) and MPFF (16%). MPFF was the most effective treatment in reducing lower leg volume, CIVIQ-20 score and pain VAS scale while calcium dobesilate and Ruscus+HMC+VitC were the most effective in reducing foot volume and ankle circumference respectively.Meta-analyses of observational studies for sulodexide showed that it improves significantly the scoring of pain, feeling of swelling, heaviness and parasthesiae measured by Likert scales. CONCLUSIONS: Sulodexide is at least as effective as pentoxifylline and more effective than MPFF in improving the rate of ulcer healing in patients with CVD. VADs are effective in improving venous symptoms and signs, as was also shown by sulodexide in the meta-analysis of observational studies. The relative effectiveness of sulodexide and VADs needs to be evaluated by an RCT in order to better inform clinical practice.

Cycling of tumor necrosis factor inhibitors versus switching to different mechanism of action therapy in rheumatoid arthritis patients with inadequate response to tumor necrosis factor inhibitors: a Bayesian network meta-analysis.

INTRODUCTION: For patients with rheumatoid arthritis (RA) with an inadequate response to tumor necrosis factor inhibitors (TNFi), main options include cycling onto a different TNFi or switching to a biologic/targeted synthetic disease-modifying antirheumatic drug with a different mechanism of action (MOA). This network meta-analysis (NMA) assessed comparative clinical efficacy of cycling versus switching. METHODS: We conducted a literature search in MEDLINE, Embase, and Cochrane Library. Outcomes included proportion of patients with 20%, 50%, or 70% response to American College of Rheumatology criteria (ACR20/ACR50/ACR70 response), Disease Activity Score in 28 joints (DAS28) score below 2.6 or between 2.6 and 3.2, mean change in DAS28 score, mean reduction in and proportion of patients achieving a clinically meaningful reduction (⩾0.22) in Health Assessment Questionnaire score, number of serious adverse events (AEs), and withdrawals for any reason/due to AEs/lack of treatment efficacy. To account for the wide range of study populations and designs, we developed three models to conduct the NMA: fixed-effect, random-effects, and hierarchical Bayesian. PROSPERO ID: CRD42019122993. RESULTS: We identified nine randomized controlled trials and 16 observational studies. The fixed-effect model suggested a 0.99 probability that switch was the better strategy for increasing odds of a clinically meaningful improvement in ACR50 [odds ratio (OR): 1.35 (95% credible interval (CI): 0.96-1.81)]. The fixed-effect model also suggested that switch was associated with lower rates of withdrawal for any reasons [OR: 0.53 (95% CI: 0.40-0.68)]. The random-effects and hierarchical Bayesian models suggested additional uncertainty as they considered more variability than the fixed-effect model. DISCUSSION: Results suggest that switching to a drug with a different MOA is more effective and associated with lower rates of withdrawal than cycling to a different TNFi after failure of first-line TNFi. Further trials that directly compare cycling with switching are warranted to better assess comparative efficacy. PLAIN LANGUAGE SUMMARY: Assessment of the effectiveness of different drug treatment strategies in patients with rheumatoid arthritis: an analysis of the published literature Rheumatoid arthritis (RA) is a chronic disease in which inflammation affects joints along with the entire body; this may cause significant pain, joint damage, physical disability, a decreased quality of life, and an increased risk of death.Tumor necrosis factor inhibitors (TNFis) are a common choice as first-line drugs to treat RA. Although they are effective in many patients, therapy with a TNFi is not successful within the first year of treatment in approximately one-third of patients due to either a lack of efficacy or safety issues.When TNFi therapy is unsuccessful, the options are to "cycle" to another TNFi or to "switch" to another drug with a different mechanism of action (MOA). Further studies are needed to help doctors decide the best treatment strategy for their patients when treatment with an initial TNFi fails.This study analyzed 25 published studies in which patients were either "cycled" to another TNFi or "switched" to a drug with a different MOA after unsuccessful treatment with an initial TNFi.The results showed that "switching" to a drug with a different MOA was a better treatment strategy than "cycling" to another TNFi; "switching" increased the chance of clinically meaningful improvement in disease status and lowered the chance of having to stop treatment for any reason.

Comparative Efficacy and Safety of Sulodexide and Other Extended Anticoagulation Treatments for Prevention of Recurrent Venous Thromboembolism: A Bayesian Network Meta-analysis.

Objective This network meta-analysis (NMA) assesses the clinical comparative efficacy and safety of sulodexide versus direct-acting oral anticoagulants (DOACs), vitamin K antagonist (VKA), and aspirin in patients with an unprovoked venous thromboembolism (VTE). Methods We conducted a literature search in MEDLINE, Embase, and Cochrane Library using both randomized controlled trials (RCTs) and observational studies. Reduction in recurrent deep venous thrombosis (r-DVT), pulmonary embolism (PE), major bleeding (MB), clinically relevant nonmajor bleeding (CRNMB) were the primary efficacy and safety outcomes. Other secondary end points were also included. We performed a fixed, random effects, and hierarchical models Bayesian NMA for each outcome. Results We identified 18 RCTs and seven observational studies. Random models showed sulodexide is the best treatment compared with DOACs, VKA, and aspirin at reducing the risk of CRNMB, for preventing death from any cause, and VTE/PE/myocardial infarction (MI)/stroke with 0.47, 0.81, and 0.65 probabilities, respectively. In the random model sulodexide was the best treatment for reducing the risk of MB with a 0.50 probability and hierarchical model that confirmed favorable results. Random and hierarchical models showed sulodexide and DOACs to be the best treatments for reducing PE risk. Sulodexide was more effective than aspirin for reducing r-DVT with 0.12 and less of 0.0001 probabilities, respectively. Conclusion Sulodexide is more effective for reducing MB and CRNMB, for preventing deaths from any cause, and from VTE/PE/MI/stroke, than other treatments, for both random and hierarchical models. Sulodexide showed to be more effective than aspirin in reducing the risk of r-DVT and PE. Sulodexide's reduction in bleeding while protecting from recurrent DVT risk makes this therapeutic option an important alternative for extended anticoagulation treatment.

Cost-effectiveness and budget impact analysis of viscosupplementation with hylan G-F 20 for knee and hip osteoarthritis.

PURPOSE: To estimate the cost-effectiveness and budget impact of viscosupplementation with one intra-articular (IA) injection of 6 mL hylan G-F 20 (Synvisc-One®) and with three injections of 2 mL hylan G-F 20 (Synvisc®3×2) in knee osteoarthritis (OA) patients compared with conventional support therapy (CST - eg, NSAIDs and acetaminophen) and the cost-effectiveness of one IA injection of 2 mL hylan G-F 20 (Synvisc®1×2) in hip OA patients compared with CST from an Italian Health System perspective. METHODS: The model used was a Markov model with states for stages II-IV on the Kellgren-Lawrence scale and runs on 6-month cycles over a 5-year time horizon. A 3.5% discount was applied to both costs and utilities. Direct costs were determined from the perspective of the Italian National Health Service. A one-way and probabilistic sensitivity analysis was conducted for both comparisons. RESULTS: Hylan G-F 20 1×6 mL and hylan G-F 20 3×2 mL for knee OA were very likely to be cost-effective when compared to acetaminophen (ICER = €3,160.61 and €3,845.81 per QALY, respectively) and NSAIDs as both ICERs are below €25,000. The hip OA treatment by hylan G-F 20 1×2 mL was dominant compared to NSAIDs and very likely compared to acetaminophen. The results of the cost-effectiveness analysis were confirmed by one-way sensitivity analysis. The budget impact analysis for knee and hip OA showed a small increase in expenditure during 5 years. CONCLUSIONS: Hylan G-F 20 1×6 mL/hylan G-F 20 is a cost-effectiveness treatment compared to NSAIDs and acetaminophen in the treatment of knee/hip OA in Italy. The treatment of hip and knee OA resulted in cost-saving with hylan G-F 20 1×2 mL and economically sustainable with hylan G-F 20 1×6 mL. However, Real Word Evidence studies should be conducted in order to estimate costs associated with both prosthetics and to understand the reduction of physiotherapy and medication due to hylan G-F 20.