Real-World Characteristics, Treatment Patterns, Health Care Resource Use, and Costs of Patients with Diffuse Large B-Cell Lymphoma in the U.S.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma in the U.S., but current real-world data are limited. This study was conducted to describe real-world characteristics, treatment patterns, health care resource utilization (HRU), and health care costs of patients with treated DLBCL in the U.S. MATERIALS AND METHODS: A retrospective study was conducted using the Optum Clinformatics Data Mart database (January 2013 to March 2018). Patients with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis for DLBCL after October 2015 and no prior International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis for unspecified DLBCL or primary mediastinal large B-cell lymphoma were classified as incident; those with such codes were classified as prevalent. An adapted algorithm identified lines of therapy (e.g., first line [1L]). All-cause HRU and costs were calculated per-patient-per-year (PPPY) among patients with a ≥1L. RESULTS: Among 1,877 incident and 651 prevalent patients with ≥1L, median age was 72 years and 46% were female. Among incident patients, 22.6% had at least two lines (2L), whereas 38.4% of prevalent patients had ≥2L. The most frequent 1L therapy was rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Incident patients had 1.3 inpatient and 42.0 outpatient (OP) visits PPPY, whereas prevalent patients had 0.8 and 31.3 visits PPPY, respectively. Total costs were $137,156 and $81,669 PPPY for incident and prevalent patients, respectively. OP costs were the main driver of total costs at $88,202 PPPY, which were higher within the first year. CONCLUSION: This study showed that a large portion of patients require additional therapy after 1L treatment to manage DLBCL and highlighted the substantial economic burden of patients with DLBCL, particularly within the first year following diagnosis. IMPLICATIONS FOR PRACTICE: Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) carry a substantial clinical and economic burden. A large portion of these patients require additional therapy beyond first-line treatment. There is significant unmet need among patients with DLBCL who require additional therapy beyond first-line treatment. Patients who do not respond to first-line therapy and are not eligible for transplants have very high health care resource utilization and costs, especially in the first 12 months following initiation of treatment.

Cost-effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam as empiric therapy based on the in-vitro surveillance of bacterial isolates in the United States for the treatment of complicated urinary tract infections.

BACKGROUND: A challenge in the empiric treatment of complicated urinary tract infection (cUTI) is identifying the initial appropriate antibiotic therapy (IAAT), which is associated with reduced length of stay and mortality compared with initial inappropriate antibiotic therapy (IIAT). We evaluated the cost-effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam (one of the standard of care antibiotics), for the treatment of hospitalized patients with cUTI. METHODS: A decision-analytic Monte Carlo simulation model was developed to compare the costs and effectiveness of empiric treatment with either ceftolozane/tazobactam or piperacillin/tazobactam in hospitalized adult patients with cUTI infected with Gram-negative pathogens in the US. The model applies the baseline prevalence of resistance as reported by national in-vitro surveillance data. RESULTS: In a cohort of 1000 patients, treatment with ceftolozane/tazobactam resulted in higher total costs compared with piperacillin/tazobactam ($36,413 /patient vs. $36,028/patient, respectively), greater quality-adjusted life years (QALYs) (9.19/patient vs. 9.13/patient, respectively) and an incremental cost-effectiveness ratio (ICER) of $6128/QALY. Ceftolozane/tazobactam remained cost-effective at a willingness to pay of $100,000 per QALY compared to piperacillin/tazobactam over a range of input parameter values during one-way and probabilistic sensitivity analysis. CONCLUSIONS: Model results show that ceftolozane/tazobactam is likely to be cost-effective compared with piperacillin/tazobactam for the empiric treatment of hospitalized cUTI patients in the United States.

Natural History and Disease Burden of Neurofibromatosis Type 1 with Plexiform Neurofibromas: A Systematic Literature Review.

Neurofibromatosis type 1 (NF1) is an incurable genetic condition that frequently includes the development of plexiform neurofibromas (PNs) in patients. A systematic literature review was conducted to identify data on the natural history, disease burden, and treatment patterns among patients diagnosed with NF1 and PN, as well as to identify evidence gaps in these areas. MEDLINE and MEDLINE In-Process, Embase, and Cochrane Library Searches were searched using predefined terms. Potential references underwent two phases of screening by two independent researchers. A total of 39 references focusing on populations of patients with both NF1 and PN were included in this review. The wide range of PN-related complications creates a substantial quality-of-life (QOL) burden for patients, including pain, social functioning, physical function impact, stigma, and emotional distress. The severe burden of NF1 with PN on the QOL of patients demonstrates the high unmet need for an effective treatment option that can reduce tumor burden and improve QOL. The heterogeneity of measurement tools used to evaluate QOL and the gap in data evaluating the health economic burden of PN should be the focus of future research.

Treatment patterns, healthcare resource utilization, and costs of patients diagnosed with primary mediastinal B-cell lymphoma in the United States.

AIMS: With the advent of ICD-10-CM codes for PMBCL on 10/01/2015, assessment of treatment patterns and healthcare burden among US patients is possible. This study sought to describe the real-world treatment patterns and economic outcomes of patients with PMBCL. METHODS: Data from the Optum Clinformatics DataMart database was used (January 2013-March 2018). Patients with a first PMBCL ICD-10-CM diagnosis (with or without an antecedent ICD-10-CM diagnosis of DLBCL/other lymphoma, which may have been assigned before PMBCL confirmation) after 10/01/2015 (index date) and no ICD-9-CM diagnosis code for unspecified PMBCL/DLBCL were identified as incident patients. Those with PMBCL ICD-10-CM and unspecified ICD-9-CM diagnosis for PMBCL/DLBCL before 10/01/2015 (index date) were identified as prevalent patients. Patients were observed from the index date up to the earliest among death, end of data availability, or end of continuous health plan enrollment. An adapted algorithm was used to identify lines of therapy (LOT). RESULTS: Among 118 incident and 30 prevalent PMBCL patients, 14% and 20% of patients received ≥2 LOTs, respectively. In incident patients, 48% received ≥1 LOT, 14% ≥2, and 4% ≥3 LOTs. Among prevalent patients, 63% received ≥1 LOT and 20% ≥2 LOTs. The most frequently recorded 1 L therapy was R-CHOP both among incident and prevalent patients. Mean total healthcare costs for incident and prevalent patients were $149,340 and $92,799 per patient per year, respectively, with higher costs ≤12 months ($187,241 and $167,553). Outpatient costs were the main driver (accounting for 60.5% and 64.6% for incident and prevalent patients, respectively). LIMITATIONS: Potential underuse of ICD-10-CM codes shortly after discontinuation of ICD-9-CM codes in 01/2015; regimens identified for each LOT using the claims-based algorithm may not reflect the regimen administered. CONCLUSION: The multiple LOTs necessary for a sizeable minority of patients and the high costs of care highlight the significant unmet needs of PMBCL patients.

Real-World Healthcare Resource Utilization in Patients with Classical Hodgkin Lymphoma Treated with Pembrolizumab and Nivolumab in the USA.

BACKGROUND: Patients with classical Hodgkin lymphoma (cHL) relapsed or refractory (R/R) disease who relapse after or are ineligible for autologous stem cell transplantation have a poor prognosis. Recently, the anti-PD1 monoclonal antibodies nivolumab and pembrolizumab were approved by the US Food and Drug Administration (FDA; May 2016 and March 2017, respectively) as treatment options for R/R cHL patients. OBJECTIVE: In the absence of comparative clinical trials between these agents, this observational study was conducted to evaluate the healthcare resource utilization (HRU) of patients with cHL initiated on pembrolizumab compared to nivolumab in the USA. PATIENTS AND METHOD: Healthcare insurance claims from Symphony Health's IDV® (Integrated Dataverse) (July 2014-June 2018) were used in this retrospective study. The study population included adult patients with cHL initiated on pembrolizumab or nivolumab (index date). Inverse probability of treatment weighting was used to adjust for differences in patient characteristics between cohorts. All-cause and cHL-related hospitalizations and outpatient visits were measured during the observation (post-index) period and reported per patient-year (PPY). Rates of HRU were compared between cohorts using rate ratios (RRs). RESULTS: A total of 92 and 218 patients initiated on pembrolizumab and nivolumab, respectively, were included in the study population. After weighting, the mean age was similar at 55 years in both cohorts, while the proportion of females was lower in the pembrolizumab cohort (35.3%) compared to the nivolumab cohort (44.1%). Mean Quan-Charlson Comorbidity Index score was well balanced after weighting in the pembrolizumab and nivolumab cohorts (4.2 and 4.3, respectively). During the observation period, patients in the pembrolizumab cohort had significantly lower rates of all-cause hospitalizations (RR [95% CI] 0.33 [0.09-0.80]) and cHL-related hospitalizations (RR [95% CI] 0.14 [0.02-0.37]) than those in the nivolumab cohort. Rates of all-cause and cHL-related outpatient visits were not statistically different between patients in the pembrolizumab and nivolumab cohorts. CONCLUSIONS: In this real-world study, adult cHL patients initiated on pembrolizumab had significantly lower rates of all-cause and cHL-related hospitalizations compared to patients initiated on nivolumab.

An Asian viewpoint on the use of vitamin D and calcium in osteoporosis treatment: physician and patient attitudes and beliefs.

BACKGROUND: Osteoporosis treatment guidelines recommend calcium and vitamin D supplementation for both prevention as well as treatment, however, compliance with these guidelines is often unsatisfactory. This study investigated the opinion of Asian physicians and Asian patients regarding vitamin D and calcium and patients' use of both. METHODS: Physicians selected from Malaysia, Taiwan, Philippines, Korea and Singapore were asked to grade the significance of vitamin D and calcium in the treatment of osteoporosis and their patients' use of these supplements. In addition, physicians recruited seven eligible osteoporotic women to answer a questionnaire to determine their use of vitamin D and calcium, and their attitudes and beliefs regarding these supplements. RESULTS: In total, 237 physicians and 1463 osteoporosis patients completed the questionnaire. The results revealed that 22% of physicians in Malaysia, 12% in Taiwan, 72% in the Philippines, 50% in Korea and 24% in Singapore rated the importance of vitamin D supplementation as being extremely important. For calcium, 27% of physicians in Malaysia, 30% in Taiwan, 80% in the Philippines, 50% in Korea and 38% in Singapore rated the importance as being extremely important. Forty-three percent of patients in Malaysia, 38% in Taiwan, 73% in the Philippines, 35% in Korea and 39% in Singapore rated the importance of vitamin D as being extremely important. For calcium, 69% of patients in Malaysia, 58% in Taiwan, 90% in the Philippines, 70% in Korea and 55% in Singapore rated the importance as being extremely important. In addition, results of the patient questionnaire revealed that only a very small number regularly took both supplements. In addition, the results indicated that, with the exception of patients from the Philippines, the majority of patients had no or infrequent discussion with their physician about vitamin D and calcium. CONCLUSIONS: There is generally suboptimal appreciation by both physicians and patients of the importance of vitamin D and calcium for maintenance of bone health as reflected in the low number of patients who reported regularly taking these supplements. Recognition of this problem should translate to appropriate action to improve education for both physicians and patients, with a goal to increase use of these supplements among Asian patients with osteoporosis.

COX-2 inhibitors: complex association with lower risk of hospitalization for gastrointestinal events compared to traditional NSAIDs plus proton pump inhibitors.

PURPOSE: To compare hospitalization rates for serious upper and lower gastrointestinal (GI) events between chronic and acute users of a traditional non-steroidal anti-inflammatory drugs (tNSAID) + proton pump inhibitor (PPI) and users of a COX-2 selective inhibitor (Coxib). METHODS: The PHARMO Record Linkage System, including linked drug-dispensing and hospital records of approximately 3 million individuals in the Netherlands was used. We selected new Coxib or tNSAID users (01/01/2000-31/12/2004) with > or =1 year history before the first NSAID dispensing and > or =1 year follow-up ending at the first hospitalization for GI event (the outcome), last dispensing, or end of the study period. Chronic users were patients who used any NSAIDs for > or =60 days during the first year (n = 58 770); others were acute users (n = 538 420). Multivariate analysis was performed by Poisson regression adjusted for gender, age, and duration of follow-up, tNSAID and Coxib dose, NSAID/PPI adherence, use of other gastroprotective agents, anticoagulants, acetaminophen, corticosteroids, and cardiovascular disease. RESULTS: The cohort included 23 999 new tNSAIDs + PPI users and 25 977 new Coxib users, with main characteristics: mean +/- SD age 58.1 +/- 15.5 vs. 56.7 +/- 17.5; female 55.3% vs. 62.2%; duration of treatment (days): 137 +/- 217 vs. 138 +/- 179, respectively. Among acute users, adjusted hazard ratios (95% Confidence Interval) were 0.21 (0.14-0.32) for upper and 0.26 (0.16-0.42) for lower GI events, for Coxib versus tNSAIDs + PPI users. Among chronic users, these were 0.35 (0.22-0.55) for upper GI and 0.43 (0.25-0.75) for lower GI events. CONCLUSIONS: Coxib users had significantly lower rates of GI events. Further research should elucidate the possible impact of selection bias.

Impact of high- versus low-dose neuromuscular blocking agent administration on unplanned 30-day readmission rates in retroperitoneal laparoscopic surgery.

Recent data shows that a neuromuscular block (NMB) induced by administration of high doses of rocuronium improves surgical conditions in certain procedures. However, there are limited data on the effect such practices on postoperative outcomes. We performed a retrospective analysis to compare unplanned 30-day readmissions in patients that received high-dose versus low-dose rocuronium administration during general anesthesia for laparoscopic retroperitoneal surgery. This retrospective cohort study was performed in the Netherlands in an academic hospital where routine high-dose rocuronium NMB has been practiced since July 2015. Charts of patients receiving anesthesia between January 2014 and December 2016 were searched for surgical cases receiving high-dose rocuronium and matched with respect to procedure, age, sex and ASA classification to patients receiving low-dose rocuronium. The primary post-operative outcome was unplanned 30-day readmission rate. There were 130 patients in each cohort. Patients in the high- and low-dose rocuronium cohorts received 217 ± 49 versus 37 ± 5 mg rocuronium, respectively. In the high-dose rocuronium group neuromuscular activity was consistently monitored; matched patients were unreliably monitored. All patients receiving high-dose rocuronium were reversed with sugammadex, while just 33% of matched patients were reversed with sugammadex and 20% with neostigmine; the remaining patients were not reversed. Unplanned 30-day readmission rate was significantly lower in the high-dose compared to the low-dose rocuronium cohort (3.8% vs. 12.7%; p = 0.03; odds ratio = 0.33, 95% C.I. 0.12-0.95). This small retrospective study demonstrates a lower incidence of unplanned readmissions within 30-days following laparoscopic retroperitoneal surgery with high-dose relaxant anesthesia and sugammadex reversal in comparison to low-dose relaxant anesthesia. Further prospective studies are needed in larger samples to corroborate our findings and additionally assess the pharmacoeconomics of high-dose relaxant anesthesia taking into account the benefits (reduced readmissions) and harm (cost of relaxants and reversal agents) of such practice.

An evaluation of patients' preferences for osteoporosis medications and their attributes: the PREFER-International study.

BACKGROUND: Patients' preferences for medications may be important in determining their compliance with therapy, particularly in the case of an asymptomatic chronic disease such as osteoporosis. Although preferences for certain attributes of osteoporosis medications, including dosing frequency and tolerability, can be evaluated in short-term clinical trials, years of use may be necessary for differences in effectiveness in reducing fracture risk to emerge. OBJECTIVES: The primary aim of this study was to evaluate the relative importance of various attributes in determining patients' preferences for osteoporosis medications. Its secondary aim was to investigate patients' preferences for either of 2 hypothetical osteoporosis medications with different profiles. METHODS: The Preference for Effective Regimens (PREFER)-International study was a cross-sectional survey of postmenopausal women with osteoporosis in France, Germany, Mexico, Spain, and the United Kingdom. Participants were recruited by their physicians in the 4 European countries and were identified by trained interviewers going door to door in Mexico. Participants were administered a questionnaire in which they were asked to rate and rank the importance of 7 medication attributes in determining their preferences for prescription osteoporosis medications. The attributes were side effects, out-of-pocket costs, effectiveness in improving bone health and preventing fractures, dosing frequency, formulation, administration procedure, and length of time on the market. They were also asked to indicate their preference for 2 hypothetical osteoporosis medications whose profiles differed in terms of efficacy (medication A reduced the risk of spine and hip fracture; medication B reduced spine fracture only), time on the market (10 years vs recently introduced), dosing frequency (weekly vs monthly), and dosing procedure (30- vs 60-minute wait after dosing). RESULTS: Of 3000 patients interviewed, 1500 were receiving prescription treatment for osteoporosis. Across the rankings and ratings, effectiveness in reducing the risk of fracture emerged as the most important factor in determining patients' preferences for prescription osteoporosis medications, followed by side effects. Out-of-pocket costs, dosing frequency, formulation, time on the market, and dosing procedure were less important considerations among respondents from most countries. The majority (78%) of patients indicated a preference for medication A over medication B. CONCLUSION: Effectiveness in reducing fracture risk was cited as the primary reason for patients' preference for prescription osteoporosis medications among postmenopausal women with osteoporosis from 4 European countries and Mexico.

Cost-effectiveness of ceftolozane/tazobactam plus metronidazole versus piperacillin/tazobactam as initial empiric therapy for the treatment of complicated intra-abdominal infections based on pathogen distributions drawn from national surveillance data in the United States.

BACKGROUND: The prevalence of antimicrobial resistance among gram-negative pathogens in complicated intra-abdominal infections (cIAIs) has increased. In the absence of timely information on the infecting pathogens and their susceptibilities, local or regional epidemiology may guide initial empirical therapy and reduce treatment failure, length of stay and mortality. The objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam + metronidazole compared with piperacillin/tazobactam in the treatment of hospitalized US patients with cIAI at risk of infection with resistant pathogens. METHODS: We used a decision-analytic Monte Carlo simulation model to compare the costs and quality-adjusted life years (QALYs) of persons infected with nosocomial gram-negative cIAI treated empirically with either ceftolozane/tazobactam + metronidazole or piperacillin/tazobactam. Pathogen isolates were randomly drawn from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database, a surveillance database of non-duplicate bacterial isolates collected from patients with cIAIs in medical centers in the USA from 2011 to 2013. Susceptibility to initial therapy was based on the measured susceptibilities reported in the PACTS database determined using standard broth micro-dilution methods as described by the Clinical and Laboratory Standards Institute (CLSI). RESULTS: Our model results, with baseline resistance levels from the PACTS database, indicated that ceftolozane/tazobactam + metronidazole dominated piperacillin/tazobactam, with lower costs ($44,226/patient vs. $44,811/patient respectively) and higher QALYs (12.85/patient vs. 12.70/patient, respectively). Ceftolozane/tazobactam + metronidazole remained the dominant choice in one-way and probabilistic sensitivity analyses. CONCLUSIONS: Based on surveillance data, ceftolozane/tazobactam is more likely to be an appropriate empiric therapy for cIAI in the US. Results from a decision-analytic simulation model indicate that use of ceftolozane/tazobactam + metronidazole would result in cost savings and improves QALYs, compared with piperacillin/tazobactam.

Association between gastrointestinal events and compliance with osteoporosis therapy.

PURPOSE: The aim of this study was to estimate the rate of gastrointestinal (GI) events, and association between GI events and compliance with osteoporosis therapy among osteoporotic women. METHODS: A retrospective cohort study using a large administrative claims database in the United States from 2001 through 2010 was conducted. We studied women ≥ 55 years old who were continuously enrolled in a health plan for at least 2 years, a baseline year before and a follow-up year after the date of the first prescription of oral bisphosphonate as the first oral osteoporosis treatment. Compliance with osteoporosis therapy was measured using the medication possession ratio (MPR), with compliance defined as MPR ≥ 0.8. Multivariate logistic regression was used to assess the association between occurrence of GI events and compliance with osteoporosis therapy after controlling for demographic and clinical characteristics. RESULTS: A sample consisting of 75,593 women taking at least one oral bisphosphonate with mean (SD) age of 64 (8) years was identified. A total of 21,142 (28%) patients experienced at least one GI event during the follow-up period. Only 31,306 (41%) patients were compliant with osteoporosis therapy. Patients who experienced GI events after initiation of oral bisphosphonates were 29% less likely to adhere to osteoporosis therapy as compared to patients who did not experience GI events (odds ratio [95% CI], 0.71 [0.69-0.74]; P < .001). CONCLUSIONS: Less than half of the patients were compliant with osteoporosis therapy within one year after initiating oral bisphosphonates, and the likelihood of compliance was significantly lower by 29% among women with GI events.

A risk assessment tool (OsteoRisk) for identifying Latin American women with osteoporosis.

OBJECTIVE: To develop a simple and easy-to-use tool for identifying osteoporotic women (femoral neck bone mineral density [BMD] T-scoresor=50 in Latin America who had femoral neck BMD measurements. MEASUREMENTS AND MAIN RESULTS: A risk index was developed from 1,547 patients based on least square regression using age, weight, history of fractures, and other variables as predictors for BMD T-score. The final model was simplified by reducing the number of predictors; sensitivity and specificity were evaluated before and after reducing the number of predictors to assess performance of the index. The final model included age, weight, country, estrogen use, and history of fractures as significant predictors for T-score. The resulting scoring index achieved 91% sensitivity and 47% specificity. Simplifying the index by using only age and weight yielded similar performance (sensitivity, 92%; specificity, 45%). Three risk categories were identified based on OsteoRisk, the index using only age and body weight: high-risk patients (index <=-2; 65.6% were osteoporotic), moderate-risk patients (-2< index <=1; 26.7% were osteoporotic), and low-risk patients (index>1; 8% were osteoporotic). Similar results were seen in a validation sample of 279 women in Brazil. CONCLUSION: Age and weight alone performed well for predicting the risk of osteoporosis among postmenopausal women. The OsteoRisk is an easy-to-use tool that effectively targets the vast majority of osteoporotic patients in Latin America for evaluation with BMD.

Gastrointestinal events and association with initiation of treatment for osteoporosis.

BACKGROUND: Preexisting gastrointestinal (GI) events may deter the use of pharmacologic treatment in patients diagnosed with osteoporosis (OP). The objective of this study was to examine the association between preexisting GI events and OP pharmacotherapy initiation among women diagnosed with OP. METHODS: The study utilized claims data from a large US managed care database to identify women aged ≥55 years with a diagnosis code for OP (index date) during 2002-2009. Patients with a claim for pharmacologic OP treatment in the 12-month pre-index period (baseline) were excluded. OP treatment initiation in the post-index period was defined as a claim for bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid), calcitonin, raloxifene, or teriparatide. During the post-index period (up to 12 months), GI events were identified before treatment initiation. A time-dependent Cox regression model was used to investigate the likelihood of initiating any OP treatment. Among patients initiating OP treatment, a discrete choice model was utilized to assess the relationship between post-index GI events and likelihood of initiating with a bisphosphonate versus a non-bisphosphonate. RESULTS: In total, 65,344 patients (mean age 66 years) were included; 23.7% had a GI event post diagnosis and before treatment initiation. Post-index GI events were associated with a 75% lower likelihood of any treatment initiation (hazard ratio 0.25; 95% confidence interval 0.24-0.26). Among treated patients (n=23,311), those with post-index GI events were 39% less likely to receive a bisphosphonate versus a non-bisphosphonate (odds ratio 0.61; 95% confidence interval 0.54-0.68). CONCLUSION: GI events after OP diagnosis were associated with a decreased likelihood of OP treatment initiation and an increased likelihood of treatment initiation with a non-bisphosphonate versus a bisphosphonate.

Cost effectiveness of alendronate for the treatment of male osteoporosis in Sweden.

BACKGROUND: One third of all the hip fractures occur in men. The risk for mortality following hip fracture is higher for men compared to women. The Fracture Intervention Trial (FIT) showed that the bisphosphonate alendronate reduces the risk of fractures and increases bone mineral density (BMD) in osteoporotic women. Similar effects of alendronate were observed in men in some other trials. There are also results demonstrating alendronate to be cost-effective in the treatment of osteoporosis in women. OBJECTIVE: To investigate the cost effectiveness of alendronate for male osteoporosis in Sweden by assuming the same relative risk reduction of fractures in men as for women, based on the FIT trial. DESIGN: A Markov model earlier used to analyze cost effectiveness of alendronate in treatment of postmenopausal osteoporosis in Sweden was adapted to fit a cohort of Swedish men. Cost effectiveness of alendronate vs. no treatment was assessed by transitioning men in the model over time between different health states. TIME HORIZON: The patients were followed from start of intervention until 100 years of age or death. In the base-case alendronate was assumed to have a fracture-risk-reducing effect for 10 years; a treatment duration period of 5 years followed by a 5-year period where the effect declined linearly to zero. RESULTS: Taking a societal perspective treating a 71-year-old man (mean age in the FIT) with low BMD and prior vertebral fracture (VFA) with alendronate was found to be associated with a cost of 14,843 per quality adjusted life year (QALY) gained. CONCLUSIONS: The results in this study indicate that treating osteoporotic men with alendronate was projected to be cost-effective, under the assumption of the same fracture-risk-reducing effect of alendronate for men as for women.

Persistence with weekly and monthly bisphosphonates among postmenopausal women: analysis of a US pharmacy claims administrative database.

BACKGROUND: Bisphosphonates are available in daily, weekly, and monthly dosing formulations to treat postmenopausal osteoporosis. Some researchers suggested that adherence to monthly bisphosphonate might be different from that with weekly or daily bisphosphonate because of different dosing regimens. However, the actual persistency rates in regular practice settings are unknown. OBJECTIVES: To compare persistence rates with alendronate 70 mg once weekly (AOW), risedronate 35 mg once weekly (ROW), and ibandronate 150 mg once monthly (IOM) in a US pharmacy claims database. METHODS: In this retrospective cohort study, pharmacy claims data of patients with new bisphosphonate prescriptions were extracted for women aged ≥ 50 years who had an AOW, ROW, or IOM prescription (index prescription) between December 30, 2004 and May 31, 2005 (the index period) and did not have the index Rx during the previous 12 months. Patients' records were reviewed for at least 5 months from their index date to November 2, 2005 (the follow-up period). Patients were considered persistent if they neither discontinued (failed to refill the index Rx within a 45-day period following the last supply day of the previous dispensing) nor switched (changed to another bisphosphonate) during the follow-up period. Medication-possession ratio was defined as days with index prescription supplies/total days of follow-up. RESULTS: Among 44,635 patients, 25,207 (56.5%) received prescriptions of AOW, 18,689 (41.9%) ROW, and 739 (1.7%) IOM as the index prescription. In all, 35.1% of AOW patients, 32.5% of ROW patients, and 30.4% of IOM patients (P < 0.0001 AOW vs ROW or IOM) had persisted with their initial therapy, whereas 64.0% of AOW, 66.4% of ROW, and 68.2% of IOM patients discontinued (P < 0.0001) during follow-up. The medication-possession ratio (days with index prescription supplies/total days of follow-up) was significantly higher for AOW (0.55) compared with ROW (0.52) and IOM (0.51, P < 0.05). By Kaplan-Meier analysis, the time for 50% of patients to discontinue therapy was also significantly longer with AOW (109 days) compared with ROW (95 days, P < 0.05) or IOM (58 days, P < 0.05). CONCLUSION: In a real-world clinical setting, although persistence with all treatments was suboptimal, patients receiving prescriptions for once-weekly alendronate were more likely to be persistent than those receiving prescriptions for once-weekly risedronate or once-monthly ibandronate.

Epidemiology of falls and osteoporotic fractures: a systematic review.

BACKGROUND AND METHODS: Fractures in elderly populations result from the combination of falls and osteoporosis. We report a systematic review of studies indexed in PubMed reporting annual rates of low-trauma falls and associated osteoporotic fractures among older community-dwelling people (age ≥ 50 years). An osteoporotic fracture was defined as either a fracture resulting from a low-impact fall in subjects with clinical osteoporosis, a fall resulting in an investigator-defined osteoporotic fracture, or a fall resulting in a low-trauma fracture. Rates are presented using descriptive statistics. Meta-analysis was conducted for statistically homogeneous data sets. RESULTS: The median (range) annual fall prevalence rates (median proportion of people who experienced one or more falls during the past year) for cohorts of women and men (10 determinations), women alone (seven determinations), and men alone (four determinations) were, respectively, 0.334 (0.217-0.625), 0.460 (0.372-0.517), and 0.349 (0.284-0.526). In studies that reported fall prevalence rates for Western men and women separately (four determinations), the pooled risk ratio (95% confidence interval [CI]) for men versus women was 0.805 (95% CI 0.721-0.900). The ranges of fall prevalence rates in East Asian women (two studies) and East Asian men (two studies) were, respectively, 0.163-0.258 and 0.087-0.184. The risk ratio (95% CI) for fall prevalence in East Asian men versus women was 0.634 (0.479-0.838) in studies (two determinations) reporting results for East Asian men and women separately. In cohorts of Western women and men (five determinations), the pooled rate (95% CI) of low-impact falls resulting in fractures was 0.041 (0.031-0.054). The proportion of low-trauma fractures attributable to falls among the Western community-dwelling elderly was within the range of 0.860-0.950 for fractures at all sites or the hip (five determinations). A range of 0.716-0.924 of all fractures were osteoporotic (eight determinations). CONCLUSION: Fall rates are higher in women than in men in Western community-dwelling populations and lower in East Asian populations. Extrapolated to the US population, the statistics imply that low-impact falls cause approximately 0.53 million osteoporotic fractures annually among the US community-dwelling elderly.

Calcium and vitamin D intake by postmenopausal women with osteoporosis in Spain: an observational calcium and vitamin D intake (CaVIT) study.

BACKGROUND: Osteoporotic fractures are important causes of morbidity, mortality, and increased health care costs. However, the risk of osteoporotic fractures can be decreased, with clinical studies supporting the use of calcium and vitamin D supplements to promote bone health. Vitamin D insufficiency is widespread, particularly among postmenopausal women with osteoporosis, and this indicates that dietary intake is suboptimal, even though vitamin D supplements are widely available. METHODS: We conducted an observational study, using telephone surveys, to estimate vitamin D and calcium intake and the use of prescription osteoporosis medications in Spanish women aged ≥ 50 years with osteoporosis. RESULTS: Among the study participants, mean dietary calcium intake was 1239 mg/day and generally appeared sufficient in terms of the recommended daily intake guidance documents. Participants aged ≥ 75 years had a significantly lower mean dietary calcium intake (988 mg/day), thus one-half were below the level advised by the World Health Organization. Daily calcium intake was also lower in participants who were not taking prescription medications for bone health. Dietary vitamin D intake was 167 IU/day, which is well below both the established target dose (400 IU/day) and the more recent, higher guideline recommended for postmenopausal women (800-1300 IU/day). Dietary vitamin D intake was even lower for participants aged ≥ 75 years (120 IU/day) and was not related to the use of bone health prescription medications. CONCLUSION: These results support the need for greater promotion of the benefits of higher vitamin D intake in Spanish women with osteoporosis.

How do physicians weigh benefits and risks associated with treatments in patients with osteoarthritis in the United Kingdom?

OBJECTIVE: To quantify the relative importance that UK physicians attach to the benefits and risks of current drugs when making treatment decisions for patients with osteoarthritis (OA). METHODS: Physicians treating at least 10 patients with OA per month completed an online discrete-choice experiment survey and answered 12 treatment-choice questions comparing medication profiles. Medication profiles were defined by 4 benefits (reduction in ambulatory pain, resting pain, stiffness, and difficulty doing daily activities) and 3 treatment-related risks [bleeding ulcer, stroke, and myocardial infarction (MI)]. Each physician made medication choices for 3 of 9 hypothetical patients (varied by age, history of MI, hypertension, and history of gastrointestinal bleeding). Importance weights were estimated using a random-parameters logit model. Treatment-related risks physicians were willing to accept in exchange for various reductions in ambulatory and resting pain also were calculated. RESULTS: The final sample was 475. A reduction in ambulatory pain from 75 mm to 25 mm (1.6 units) was 1.1 times as important as an increase in MI risk from 0% to 1.5% (1.5 units). The greatest importance was for eliminating a 3% treatment-related risk of MI or stroke. On average, physicians were willing to accept an increase in bleeding ulcer risk of 0.7% (95% CI 0.4%-1.7%) for a reduction in ambulatory pain of 75 mm to 50 mm. CONCLUSION: When presented with well-known benefits and risks of OA treatments, physicians placed greater importance on the risks than on the analgesic properties of the drug. This has implications for the reporting of the results of clinical research to physicians.

Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: a meta-analysis.

BACKGROUND: The efficacy of vitamin D(3) in preventing fractures and falls has been explored in a number of clinical trials. However, recent evidence revealed new questions about the adequate doses of vitamin D(3) supplementation and its efficacy in fracture prevention independent of calcium supplements for various types of fractures. OBJECTIVE: To conduct a meta-analysis to estimate the effectiveness of 800 IU daily vitamin D(3) supplementation for increasing bone mineral density (BMD) and preventing fractures in postmenopausal women. METHODS: Medline and EMBASE were searched for controlled trials comparing the effectiveness of cholecalciferol (vitamin D(3)) against placebo with or without background calcium supplementation in the treatment of postmenopausal women. RESULTS: Eight controlled trials evaluating the effect of vitamin D(3) supplementation with or without calcium were assessed. Of 12 658 women included in a Bayesian meta-analysis, 6089 received vitamin D(3) (with or without calcium) and 6569 received placebo (with or without calcium). Compared to placebo, vitamin D(3) with calcium supplementation showed beneficial effects on the incidence of non-vertebral (odds ratio [OR] 0.77, 95% credibility limit [CL] 0.6-0.93) and hip (OR 0.70, 95% CL 0.53-0.90) fractures, while the effects on non-vertebral-non-hip fractures (OR 0.84, 95% CL 0.67-1.04) % point increase) were associated with more uncertainty. Vitamin D(3) supplementation showed a 70% probability of being a better treatment than placebo for the prevention of non-vertebral fractures, hip fractures, and non-vertebral, non-hip fractures. Compared to calcium supplementation, vitamin D(3) plus calcium reduced non-vertebral fractures (OR 0.68, 95% CL 0.43-1.01) and non-vertebral, non-hip fractures (OR 0.64, 95% CL 0.38-0.99), but did not reduce hip fractures (OR 1.03, 95% CL 0.39-2.25). Key limitations to this analysis include a small number of studies and heterogeneity in the study populations. CONCLUSIONS: This meta-analysis supports the use of vitamin D3 of 800 IU daily to reduce the incidence of osteoporotic non-vertebral, hip, and non-vertebral-non-hip fractures in elderly women. Vitamin D(3) with calcium appears to achieve benefits above those attained with calcium supplementation alone for non-vertebral and non-vertebral-non-hip fractures.

Cost-effectiveness of a fixed dose combination of alendronate and cholecalciferol in the treatment and prevention of osteoporosis in the United Kingdom and The Netherlands.

OBJECTIVE: To evaluate the cost-effectiveness of a fixed dose combination of alendronate 70 mg and cholecalciferol 2800 IU (alendronate/vitamin D3; Fosavance) versus no treatment, alendronate with dietary vitamin D supplements and ibandronate in the treatment of osteoporosis in the UK and Netherlands. METHODS: A patient simulation model was developed. One-year cycles included health states related to hip, vertebral, wrist and proximal humerus fractures, as well as death due to hip fractures and other causes. Effect of treatment was extracted from alendronate and ibandronate clinical trials. Direct costs and utilities were derived from other literature. Analyses were performed for women with a history of vertebral fractures and osteoporosis aged 50, 60, 70 and 80 years. Probabilistic sensitivity analyses were undertaken to estimate the uncertainty of outcomes. RESULTS: In the UK, alendronate/vitamin D3 was cost-effective compared to no treatment in women 70 years and older with osteoporosis ( pound17 439 per quality-adjusted life year [QALY] gained) and women 60 years and older with a history of vertebral fractures ( pound29 283 per QALY gained). For women 80 years of age alendronate/vitamin D3 was cost-saving combined with QALY gains. Alendronate/vitamin D3 was cost-saving relative to alendronate with dietary supplements. Relative to ibandronate, alendronate/vitamin D3 was cost-effective in women 50 years ( pound19 095 per QALY gained) and economically dominant in women 60 years or older. Comparable results were observed for the Netherlands. CONCLUSIONS: Given the underlying assumptions and data used, this economic modelling study showed that alendronate/vitamin D3 is cost-effective in women 70 years or older with osteoporosis and in women 60 years or older with a history of vertebral fractures in the UK and Netherlands. Alendronate/vitamin D3 is economically dominant over ibandronate in women with a history of vertebral fractures aged 60 and over and cost-saving relative to alendronate with dietary supplements.