Comparative effectiveness and cardiovascular safety of abaloparatide and teriparatide in postmenopausal women new to anabolic therapy: A US administrative claims database study.

Real-world evidence on the comparative effectiveness and safety of abaloparatide versus teriparatide in women with osteoporosis may help inform treatment decisions. Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of nonvertebral fractures, resulted in a 22% risk reduction for hip fractures, and demonstrated similar cardiovascular safety. Osteoporotic fracture risk can be reduced with anabolic or antiresorptive medications. In addition to efficacy and safety data from controlled clinical trials, real-world evidence on comparative effectiveness and safety may help inform treatment decisions. INTRODUCTION: The real-world effectiveness of abaloparatide versus teriparatide on nonvertebral fracture (NVF) incidence and cardiovascular safety during the 19-month period after treatment initiation were evaluated (NCT04974723). METHODS: Anonymized US patient claims data from Symphony Health, Integrated Dataverse (IDV)®, May 1, 2017 to July 31, 2019, included women aged ≥ 50 years with ≥ 1 prescription of abaloparatide or teriparatide and no prior anabolic therapy. Most were enrolled in commercial and Medicare health plans. Index was the date of the initial prescription dispensed during the identification period. In 1:1 propensity score matched cohorts, time to first NVF following index date, major adverse cardiovascular events (MACE), and MACE + heart failure (HF) were compared between cohorts using a Cox proportional hazards model. RESULTS: Propensity score matching yielded 11,616 patients per cohort. Overall median age (interquartile range) was 67 (61, 75) years, and 25.6% had a fracture history. Over 19 months, 335 patients on abaloparatide and 375 on teriparatide had a NVF (hazard ratio [95% confidence interval]: 0.89 [0.77, 1.03]), and 121 and 154 patients, respectively, had a hip fracture [HR (95% CI): 0.78 (0.62, 1.00)]. The MACE and MACE + HF rates were similar between cohorts. CONCLUSIONS: Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of NVF and similar cardiovascular safety was demonstrated between cohorts.

Tools in the assessment of sarcopenia.

This review provides a framework for the development of an operational definition of sarcopenia and of the potential end points that might be adopted in clinical trials among older adults. While the clinical relevance of sarcopenia is widely recognized, there is currently no universally accepted definition of the disorder. The development of interventions to alter the natural history of sarcopenia also requires consensus on the most appropriate end points for determining outcomes of clinical importance which might be utilized in intervention studies. We review current approaches to the definition of sarcopenia and the methods used for the assessment of various aspects of physical function in older people. The potential end points of muscle mass, muscle strength, muscle power, and muscle fatigue, as well as the relationships between them, are explored with reference to the availability and practicality of the available methods for measuring these end points in clinical trials. Based on current evidence, none of the four potential outcomes in question is sufficiently comprehensive to recommend as a uniform single outcome in randomized clinical trials. We propose that sarcopenia may be optimally defined (for the purposes of clinical trial inclusion criteria as well as epidemiological studies) using a combination of measures of muscle mass and physical performance. The choice of outcome measures for clinical trials in sarcopenia is more difficult; co-primary outcomes, tailored to the specific intervention in question, may be the best way forward in this difficult but clinically important area.

Biomarkers and personalised medicine in rheumatoid arthritis: a proposal for interactions between academia, industry and regulatory bodies.

Rheumatoid arthritis (RA) is one of the most appropriate conditions for the application of personalised medicine as a high degree of heterogeneity has been recognised, which remains to be explained. Such heterogeneity is also reflected in the large number of treatment targets and options. A growing number of biologics as well as small molecules are already in use and there are promising new drugs in development. In order to make the best use of treatment options, both targeted and non-targeted biomarkers have to be identified and validated. To this aim, new rules are needed for the interaction between academia and industry under regulatory control. Setting up multi-centre biosample collections with clear definition of access, organising early, possibly non-committing discussions with regulatory authorities, and defining a clear route for the validation, qualification and registration of the biomarker-drug combination are some of the more critical areas where effective collaboration between the drug industry, academia and regulators is needed.

The need for a transparent, ethical, and successful relationship between academic scientists and the pharmaceutical industry: a view of the Group for the Respect of Ethics and Excellence in Science (GREES).

UNLABELLED: This paper provides recommendations for fair and unbiased relationship between academic scientists and the pharmaceutical industry. INTRODUCTION: Real or perceived problems in the relationship between academics and the industry have been the subject of much recent debate. It has been suggested that academic clinicians should sever all links with the industry-a view that is rarely challenged. METHODS: Academic experts and members of the pharmaceutical industry were invited to an expert consensus meeting to debate this topic. This meeting was organized by the Group for the Respect of Ethics and Excellence in Science. Conflict of interest, competing interest, right and duties of academic scientist, authorship, and staff and student education were discussed. RESULTS: Guidelines for a transparent, ethical, strong, and successful partnership between the academic scientist and the pharmaceutical industry have been provided. CONCLUSIONS: The Group support interactions between the industry and clinicians provided that it is transparent and ethical.

Evaluation of vertebral fracture assessment by dual X-ray absorptiometry in a multicenter setting.

SUMMARY: The utility of vertebral fracture assessment (VFA) by DXA to detect prevalent vertebral fracture in a multicenter setting was investigated by comparison to conventional radiography. While limited by lower image quality, overall performance of VFA was good but had a tendency to miss mild prevalent fractures. INTRODUCTION: In osteoporosis clinical trials standardized spine radiographs are used to detect vertebral fractures as a study endpoint. Lateral spine imaging with dual X-ray absorptiometry (DXA) scanners, known as vertebral fracture assessment (VFA) by DXA, presents a potential alternative to conventional radiography with lower radiation dose and greater patient convenience. METHODS: We investigated in a multicenter setting the ability of VFA to detect fractures in comparison with conventional radiography. The study examined 203 postmenopausal women who had imaging of the spine by DXA and radiography. Three radiologists experienced in vertebral fracture assessment independently read the VFA scans and radiographs using the Genant semiquantitative method on two occasions. CONCLUSIONS: Analyzing the data from all readable vertebrae, the kappa statistic, sensitivity, and specificity ranged from 0.64-0.77, 0.65-0.84, and 0.97-0.98, respectively. Considering only moderate and severe fractures improved the kappa statistic (0.80-0.91) and sensitivity (0.70-0.86). While image quality of VFA is inferior to radiography, the detection of vertebral fractures using visual scoring is feasible. However, VFA underperformed due to unreadable vertebrae and reduced sensitivity for mild fractures. Nevertheless, VFA correctly identified most moderate and severe vertebral fractures. Despite this limitation, VFA by DXA provides an important tool for clinical research.

Effectiveness of instant vertebral assessment to detect prevalent vertebral fracture.

INTRODUCTION: Vertebral fracture is currently underdiagnosed, despite its common severity and its value to predict further osteoporotic fracture. Morphometry using dual X-ray absorptiometry (DXA) [vertebral fracture assessment (VFA)] is a new technique that may facilitate detection of many vertebral fractures, as images are obtained at the same time as bone mineral density (BMD) measurement, and would also allow avoiding spine radiographs. METHODS: We conducted a cross-sectional study to assess the diagnostic value of Instant Vertebral Assessment (IVA), which is a morphometry scan using the Hologic Delphi densitometer, to detect prevalent vertebral fracture in postmenopausal women. Interobserver precision was assessed, then IVA scans were compared with lateral spine radiographs, considered the gold standard, to test diagnostic agreement between the two techniques. Sensitivity, specificity and predictive values were calculated, as well as the likelihood ratio of the positive test, using sensitivity and specificity at each vertebral level. RESULTS: Among 85 patients of whom 50% had at least one vertebral fracture identified with radiographs, we found that interobserver precision was moderate, with frequent difficulties in discerning upper thoracic vertebrae. On a per-vertebra basis, sensitivity was around 70% from L4 to T11 and lower above T11 whereas specificity was above 90% for all vertebrae, and the negative predictive value remained above 80% from L4 to T7 and decreased above T7. On a per-patient basis, sensitivity was 0.69, specificity 0.74, positive predictive value equalled 0.72 and negative predictive value 0.71. When only grades 2 and 3 fractures were considered, results were comparable, with slightly improved specificity. Then, with the likelihood ratios calculated in our sample, we obtained posttest probabilities using the prevalence of vertebral fracture at lumbar and thoracic levels in a large sample of postmenopausal women with osteopenia and osteoporosis with and without vertebral fracture [baseline data in women of the Multiple Outcomes on Raloxifene Evaluation (MORE) trial]. At levels where fractures were most common, likelihood ratios of the positive test were good or excellent, associated with sizeable posttest probabilities. CONCLUSION: IVA allowed diagnosis of vertebral fracture at levels where vertebral fracture were most common, i.e., the lumbar and mid and lower thoracic levels, but its value was weaker at the upper thoracic levels.

Clinically favorable effects of raloxifene on bone mineral density and serum lipids: population assessment via bivariate analysis.

Introduction: Raloxifene is a nonsteroidal benzothiophene derivative that is classified as a selective estrogen receptor modulator (SERM). It has clinical promise because of its actions as an estrogen-agonist on bone and serum lipids and an estrogen-antagonist on the breast and uterus.Objectives: To determine the percentage of women who respond to raloxifene therapy with regard to bone mineral density (BMD) and serum low density lipoprotein cholesterol (LDL-C) concentration in a large population of healthy postmenopausal women.Methods: Pooled 24-month interim data from two multicenter, placebo-controlled, double-blind phase III studies were used in this analysis. The study population included 1145 healthy women, 45-60 years of age and 2-8 years postmenopausal, randomized to receive either placebo, raloxifene (RLX) 30 mg/day, RLX 60 mg/day, or RLX 150 mg/day. Changes in BMD, measured by dual x-ray absorptiometry, and serum LDL-C concentration, measured by enzymatic assay, were analyzed simultaneously by plotting the median percentage change (baseline to endpoint) in BMD of the lumbar spine and total hip on the y-axis against the corresponding median percentage change in serum LDL-C on the x-axis for each subject in the placebo group and each of the raloxifene groups. The data localized to one of four quadrants on the plot, the upper-left quadrant representing clinically favorable shifts (increased BMD and decreased LDL-C) and the lower-right quadrant representing clinically unfavorable shifts (decreased BMD and increased LDL-C). The bivariate mean, 50th and 95th percentile ellipses, and the percentage of patients improving in one, both, or neither of the measured parameters are displayed.Results: At the end of 24 months, the bivariate mean and the 50th and 95th percentile ellipses of the placebo group for lumbar spine BMD and LDL-C were shifted to the clinically unfavorable quadrant of the plot, reflecting a decrease in BMD and an increase in LDL-C. In contrast, the bivariate mean for all raloxifene groups had shifted to the clinically favorable quadrant of the plot, reflecting an increase in BMD and a decrease in LDL-C. There was a statistically significant difference (Hotelling-Lawley test, P <.001) in the bivariate mean for all doses of raloxifene compared to placebo. Only 19.1% of subjects in the placebo group exhibited improvement in both lumbar spine BMD and LDL-C, whereas 43.5%, 47.4%, and 49.8% of subjects in the RLX 30, RLX 60, and RLX 150 group, respectively, exhibited improvement in both of these variables. Furthermore, 35.9% of subjects in the placebo group exhibited no improvement in either lumbar spine BMD or LDL-C, whereas only 13.7%, 10.1%, and 11.6% of subjects in the RLX 30, RLX 60, and RLX 150 groups, respectively, exhibited no improvement in either of these variables. Similar results were obtained comparing total hip BMD and LDL-C.Conclusions: Compared with placebo, raloxifene has beneficial effects on BMD and LDL-C in a large sample of healthy postmenopausal women. Thus, insofar as these intermediate endpoints predict disease outcomes, long-term therapy with raloxifene may be beneficial in the prevention of osteoporosis and cardiovascular diseases.