Bamlanivimab and Etesevimab Improve Symptoms and Associated Outcomes in Ambulatory Patients at Increased Risk for Severe Coronavirus Disease 2019: Results From the Placebo-Controlled Double-Blind Phase 3 BLAZE-1 Trial.

Background: In the phase 2/3 BLAZE-1 trial, bamlanivimab and etesevimab together reduced coronavirus disease 2019 (COVID-19)-related hospitalizations and any-cause mortality in ambulatory patients. Herein, we assess the impact of bamlanivimab and etesevimab treatment on the severity and length of symptoms and health outcomes among patients at increased risk for severe COVID-19. Methods: In the phase 3 portion of BLAZE-1 (NCT04427501), symptomatic patients with increased risk for severe COVID-19 were randomized (2:1) to a single infusion of 700 mg bamlanivimab and 1400 mg etesevimab or placebo. Hospitalization events, vital signs, and symptomatology were monitored throughout the trial. Results: Overall, 769 patients were randomized to bamlanivimab and etesevimab together (n = 511) or placebo (n = 258). The time to sustained symptom resolution was significantly shorter among patients who received bamlanivimab and etesevimab compared with placebo (8 vs 10 days; P < .01). The median time to first sustained symptom resolution of body aches and pain, chills, fatigue, feeling feverish, headache, and shortness of breath was significantly different in patients receiving bamlanivimab and etesevimab compared to placebo (P < .05). The proportion of patients who experienced COVID-19-related hospitalization by day 29 was significantly reduced among the bamlanivimab and etesevimab group compared with placebo (0.8% vs 5.4%; P < .01). The mean duration of hospital stay was numerically shorter among patients who received bamlanivimab and etesevimab (7.3 vs 13.5 days; P = .16), with fewer intensive care admissions. Conclusions: Patients receiving bamlanivimab and etesevimab together resolved their symptoms more rapidly than those receiving placebo. Bamlanivimab and etesevimab treatment was associated with reduced rates of hospitalizations and shorter hospital stays. Clinical Trials Registration: NCT04427501.

Patient Preferences for Biologic and Biosimilar Osteoporosis Treatments in Colombia.

PURPOSE: Teriparatide is used to treat patients with established osteoporosis but is often reserved for patients who have inadequate response to antiresorptive therapy. Biosimilar teriparatide, which is believed to have efficacy and safety similar to the originator product, is now available in Colombia. However, little is known about patients' preferences for originator biologic and biosimilar treatments. Our objective was to quantify the relative importance that patients in Colombia place on features of injectable osteoporosis treatments including whether the treatment is an originator biologic or a biosimilar. PATIENTS AND METHODS: We used a discrete choice experiment (DCE) to elicit preferences of patients with osteoporosis treatment devices in Colombia. The survey was completed by 200 respondents at high risk of fracture, with or without teriparatide experience. Each treatment alternative within the DCE was characterized by five attributes: type of medicine (originator biologic, biosimilar), needle length, angle of injection, how to measure the medicine dose, and how long the medicine can be left unrefrigerated. A random parameters logit regression was used to estimate preferences and conditional relative attribute importance, while controlling for preference heterogeneity. RESULTS: A total of 200 patients (mean age = 58.3 years) completed the survey. Most were female (84.5%) and married (54.5%); 50.5% had secondary education or less, 21% had current teriparatide exposure. The attribute with the highest conditional relative importance estimate (standard error) was biologic versus biosimilar (10 [1.11]), followed by needle length (8.06 [1.11]), dose measurement (6.38 [0.87]), refrigeration (3.81 [1.18]), and angle of injection (1.30 [0.66]). Unobserved preference heterogeneity was present and controlled for in the analyses. CONCLUSION: Despite the availability of biosimilar teriparatide in Colombia, patients expressed a strong preference for an originator biologic osteoporosis medicine over a biosimilar osteoporosis medicine, when the efficacy, safety, and cost of the two options were assumed to be the same.

A modeling framework for the economic evaluation of baricitinib in moderate-to-severe rheumatoid arthritis.

Objectives: The approval in more than 50 countries of baricitinib, an oral Janus Kinase inhibitor for the treatment of Rheumatoid Arthritis (RA), warrants a framework for corresponding economic evaluations. To develop a comprehensive economic model assessing the cost-effectiveness of baricitinib for the treatment of moderately-to-severely active RA patients in comparison to other relevant treatments, considering the natural history of the disease, real world treatment patterns, and clinical evidence from the baricitinib trials.Methods: A systematic literature review of previously developed models in RA was conducted to inform the model structure, key modeling assumptions and data inputs. Consultations with rheumatologists were undertaken to validate the modeling approach and underlying assumptions.Results: A discrete event simulation model was developed to international best practices with flexibility to assess the cost-effectiveness of baricitinib over a lifetime in a variety of markets. The model incorporates treatment sequencing to adequately reflect treatment pathways in clinical practice. Outcomes assessed include cost and quality-adjusted life years, allowing for a full incremental analysis of cost-effectiveness of competing treatments and treatment sequences.Conclusion: The economic model developed provides a robust framework for future analyses assessing the cost-effectiveness of baricitinib for the treatment of RA in specific country settings.

A risk scoring system to predict coronary stent thrombosis.

OBJECTIVE: Stent thrombosis (ST) is a potentially life-threatening complication of percutaneous coronary intervention (PCI). We aimed to develop a scoring system to predict the risk of ST following PCI. RESEARCH DESIGN AND METHODS: Odds ratios (ORs) for risk factors associated with ST were identified from a meta-analysis based on a systematic literature review, and through consensus expert opinion (Delphi-RAND method). The combined ORs were used to calculate risk scores for acute (within 24 hours), early (within 30 days) and late (31 days to 1 year) ST. Risk scores were validated against patient-level data from the TRITON-TIMI 38 study. Twenty risk factors were identified. RESULTS: The most highly predictive factor for early and late ST was "incomplete duration of dual antiplatelet therapy". Derived total risk scores ranged from 0 to 22 for acute and early ST, and from 0 to 20 for late ST. Increasing scores were associated with an increasing risk of ST when applied to trial data. Model discrimination was 0.60 (p = .0028), 0.67 (p < .0001) and 0.66 (p < .0001) for acute, early and late ST respectively, indicating good discriminatory power for predicting ST. Key limitations included a lack of published data on acute ST, resulting in a risk score for this time point being based predominantly on expert opinion, and that it was not possible to map all risk factors to variables collected in the TRITON-TIMI 38 study. CONCLUSION: Our weighted scoring system may help to stratify ST risk and individualize antiplatelet therapy in patients undergoing PCI.

Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia).

PURPOSE: To systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia). MATERIALS AND METHODS: Medline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood-lipid profile; occurrence of adverse events; and change in quality of life or pain). Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis. RESULTS: Of the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies) were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications), but not the hip region (eight publications), a low incidence of vertebral fracture (three publications), decreases in markers of bone turnover (eleven publications), improved hip structural geometry (two publications), improved blood-lipid profiles (five publications), a low incidence of hot flushes, leg cramps, venous thromboembolism, and stroke (12 publications), and improved quality of life and pain relief (one publication). CONCLUSION: Findings support raloxifene for reducing vertebral fracture risk by improving BMD and reducing bone turnover in postmenopausal Japanese women with osteoporosis or osteopenia. Careful consideration of fracture risk and the risk-benefit profile of antiosteoporosis medications is required when managing patients with osteoporosis.

Prasugrel vs clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a model-based cost-effectiveness analysis for Germany, Sweden, the Netherlands, and Turkey.

OBJECTIVE: To evaluate the long-term cost-effectiveness of 12-months treatment with prasugrel vs clopidogrel from four European healthcare systems' perspectives (Germany, Sweden, the Netherlands, and Turkey). METHODS: In the TRITON-TIMI 38 trial, patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) were treated with prasugrel or clopidogrel. Prasugrel reduced the composite end-point (cardiovascular death, MI, or stroke), but increased TIMI major bleeding. A Markov model was constructed to facilitate a lifetime horizon for the analysis. A series of risk equations constructed using individual patient data from TRITON-TIMI 38 was used to estimate risks of clinical events. Quality-adjusted life-years (QALYs) were derived by weighting survival time by estimates of health-related quality-of-life. Incremental cost-effectiveness is presented based on differences in treatments' mean costs and QALYs for the licensed population in TRITON-TIMI 38, and the sub-groups of UA-NSTEMI, STEMI, diabetes, and the 'core clinical cohort' (<75 years, ≥60 kg, no history of stroke or TIA). RESULTS: Mean cost of study drug was €364 (Turkey) to €818 (Germany) higher for prasugrel vs clopidogrel. Rehospitalization costs at 12 months were lower for prasugrel due to reduced rates of revascularization, although hospitalization costs beyond 12 months were higher due to longer life expectancy associated with lower rates of non-fatal MI in the prasugrel group. The incremental cost per QALY saved with prasugrel in the licensed population ranged from €6520 (for Sweden) to €14,350 for (Germany). Prasugrel's cost per QALY was more favourable still in the STEMI and diabetes sub-groups of the licensed population. LIMITATIONS: Probabilistic analyses of the whole trial population is impractical due to the number of individual patient profiles over which population level results are calculated. CONCLUSION: Among patients undergoing PCI for ACS, treatment with prasugrel compared with clopidogrel resulted in favourable cost-effectiveness profiles from these healthcare systems' perspectives.

Adherence and persistence with once-daily teriparatide in Japan: a retrospective, prescription database, cohort study.

Adherence and persistence with osteoporosis treatments are essential for reducing fracture risk. Once-daily teriparatide is available in Japan for treating osteoporosis in patients with a high risk of fracture. The study objective was to describe real-world adherence and persistence with once-daily teriparatide 20 µg during the first year of treatment for patients who started treatment during the first eight months of availability in Japan. This prescription database study involved patients with an index date (first claim) between October 2010 and May 2011, a preindex period ≥6 months, and a postindex period ≥12 months and who were aged >45 years. Adherence (medication possession ratio (MPR)) and persistence (time from the start of treatment to discontinuation; a 60-day gap in supply) were calculated. A total of 287 patients started treatment during the specified time period; 123 (42.9%) were eligible for inclusion. Overall mean (standard deviation) adherence was 0.702 (0.366), with 61.0% of patients having high adherence (MPR > 0.8). The percentage of patients remaining on treatment was 65.9% at 180 days and 61.0% at 365 days. Our findings suggest that real-world adherence and persistence with once-daily teriparatide in Japan are similar to that with once-daily teriparatide in other countries and with other osteoporosis medications.