Characteristics, treatment patterns, healthcare resource use, and costs among pediatric patients diagnosed with neurofibromatosis type 1 and plexiform neurofibromas: a retrospective database analysis of a medicaid population.

OBJECTIVES: The objectives of this study were to describe the characteristics and initial treatment patterns, healthcare resource use (HCRU), and costs of patients newly diagnosed with neurofibromatosis type 1 (NF1)-related plexiform neurofibromas (PN). METHODS: This was a retrospective study of individuals enrolled in the IBM MarketScan Multi-State Medicaid database from 1 October 2014 to 31 December 2017. Patients aged ≤18 years at the index date (first diagnosis of NF1 or PN, whichever occurred later) with at least 1 ICD-10-CM diagnosis code for both NF1 and PN were included. All-cause HCRU and the associated direct costs during the follow-up period were calculated per patient per year (PPPY) in 2018 USD. RESULTS: A total of 383 patients were included with a mean follow-up of 448 days. Most patients were diagnosed by a specialist (63.5%). During the follow-up period, pain medications were used by 58.5% of patients, 25.1% were treated with chemotherapy, 7.1% received surgery for PN, 1.6% received MEK inhibitors, and 0.8% received radiation. Mean PPPY inpatient, outpatient, ER, pharmacy, and other visits were 1.4, 17.3, 1.6, 13.6, and 25.8, respectively. Mean ± SD (median) total PPPY healthcare costs were $17,275 ± $61,903 ($2889), with total medical costs of $14,628 ± $56,203 ($2334) and pharmacy costs of $2646 ± $13,303 ($26). CONCLUSIONS: This study showed that many pediatric patients newly diagnosed with NF1 and PN were initially treated with supportive care only, highlighting a substantial unmet medical need. This study also highlights the considerable economic burden among patients with NF1 and PN.

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 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.

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.

Association of clinico-genomic characteristics with tumor mutational burden in small cell lung cancer patients.

Aim: We evaluated the relationship between clinical and genomic characteristics and tumor mutational burden (TMB) in small cell lung cancer. Materials & methods: In a retrospective analysis of small cell lung cancer patients aged ≥18, we assessed treatment patterns and survival in relation to TMB; the association of clinical and genomic characteristics with TMB was determined by multivariate regression. High TMB (TMB-H) was defined as ≥10 mutations/megabase. Results: Among 186 patients, treatment patterns and overall survival were similar for TMB-H and non-TMB-H patients. TMB was determined for 179 patients, 41.9% of whom were TMB-H. Short variants of LRP1B, FAT3, MLL3, MED12 and NOTCH3 were significantly associated with TMB-H (p ≤ 0.01). Conclusion: Neither treatment patterns nor survival differed by TMB status.

Treatment, Resource Use and Costs Among Pediatric Patients with Neurofibromatosis Type 1 and Plexiform Neurofibromas.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition which predisposes individuals to tumors of the nervous system, skin, bones, and eyes. Plexiform neurofibromas (PNs) occur in 20-50% of NF1 cases, causing multiple morbidities and conferring a risk of malignancy. NF1 with PN is poorly characterized in the literature with regard to treatment patterns, healthcare resource utilization, and costs in the real world. METHODS: This was a retrospective analysis of data from a commercial claims database in the US between October 2014 and March 2018. Persons with at least 1 diagnostic code for both NF1 and PN, aged ≤18 years on the index date, and continuously enrolled for ≥12 months before the index date were included. The index date was defined as the date of the first diagnosis of NF1 or PN during the study period, whichever occurred later. Healthcare resource utilization during follow-up included outpatient, inpatient, emergency room (ER), and pharmacy encounters; corresponding costs were calculated as the mean per patient per year (PPPY) in 2018 US dollars. Treatments were classified as PN surgery, pain medication, chemotherapy, radiotherapy, and targeted therapies. All analyses were descriptive. RESULTS: A total of 301 patients were included. In the follow-up period, nearly all patients (99.7%) had outpatient visits, while 81.1% had pharmacy visits, 25.2% had ER visits, and 13.0% had inpatient visits. Mean ± SD [median] total healthcare costs PPPY were $38,292 ± $80,556 [$16,037]. During follow-up, 44.2% of patients used pain medications, 23.9% received chemotherapy, 5.0% underwent surgery for PN, 1.3% received radiotherapy, and 1.0% received targeted therapies. CONCLUSION: Commercially insured pediatric patients diagnosed with NF1 and PN were treated primarily with supportive care, highlighting a substantial unmet need in the United States.

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.

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.

Reasons for Not Treating Women with Postmenopausal Osteoporosis with Prescription Medications: Physicians' and Patients' Perspectives.

BACKGROUND: In the United States, between one-third and two thirds of postmenopausal women do not begin treatment with a prescription osteoporosis medication after a diagnosis of osteoporosis. The objective of this study was to understand the reasons for this lack of treatment. MATERIALS AND METHODS: Online physician and patient surveys were administered in 2013. The physician survey included a chart review of untreated postmenopausal women recently diagnosed with osteoporosis and gathered data on physicians' practices regarding the management of osteoporosis in postmenopausal women. The patient survey was given to untreated postmenopausal women with a recent osteoporosis diagnosis. RESULTS: The physician survey was completed by 224 physicians, who also reviewed 811 patient charts. A total of 165 patients completed the patient survey. In the chart review, physicians reported that 19% of the postmenopausal women they diagnosed with osteoporosis were not prescribed an osteoporosis medication. The patient declined a physician's recommendation for pharmacological treatment in 81% and 52% of cases in the physician and patient surveys, respectively. The most frequent reasons for physicians not recommending treatment were: low calcium and/or vitamin D levels, patients potentially at risk of medication side effects, pre-existing gastrointestinal problems, and polypharmacy. The most frequent reasons for patients deciding against treatment were: concerns about side effects, considering nonprescription options and behavioral modifications, and questioning the potential benefit of taking the medication. CONCLUSIONS: Patients decided against pharmacological treatment of newly diagnosed osteoporosis in at least half of the cases of nontreatment. The principal reasons for not being treated with a prescription medication, given by both physicians and patients, were that there were alternatives and concern about the risks of prescription medications.

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.

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.

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.

Rationale and design of MUSIC OS-EU: an international observational study of the treatment of postmenopausal women for osteoporosis in Europe and Canada.

OBJECTIVES: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS-EU) was designed to better understand the rate and burden of gastrointestinal (GI) events on clinical and health care outcomes among postmenopausal women with osteoporosis. METHODS: MUSIC OS-EU is a prospective, multinational, observational cohort study of postmenopausal women ≥50 years of age diagnosed with osteoporosis and enrolled in physician clinics in six countries: France, Italy, the Netherlands, Sweden, the United Kingdom, and Canada. The MUSIC OS-EU study has three components: (i) a physician survey to describe their management of osteoporotic patients with GI events; (ii) a retrospective chart survey to describe the receipt and type of osteoporosis medication prescribed; and (iii) a prospective cohort study including untreated and treated patients diagnosed with osteoporosis to investigate the rate of GI events and association with osteoporosis medication use patterns, health-related quality of life, treatment satisfaction and resource utilisation among postmenopausal women with osteoporosis. RESULTS: Physicians at 97 sites completed the physician questionnaire and data for 716 patients were abstracted for the retrospective chart review. Enrolment and the baseline data collection for the prospective cohort study were conducted between March 2012 and June 2013 for 292 untreated and 2,959 treated patients, of whom 684 were new users and 2,275 were experienced users of oral osteoporosis medications. CONCLUSIONS: The results of MUSIC OS-EU will illuminate the association of GI events with the management of osteoporosis and with patient-reported outcomes among postmenopausal women with osteoporosis in Europe and Canada.

Cost and consequences of noncompliance with osteoporosis treatment among women initiating therapy.

OBJECTIVE: The objective was to evaluate compliance with osteoporosis (OP) treatments and determine the fracture and healthcare burden associated with noncompliance. METHODS: This retrospective analysis of a US claims database identified women initiating an OP medication from 1 January 2002 to 30 June 2009. Patients were ≥55 years and had ≥1 pharmacy claim for a bisphosphonate or non-bisphosphonate (raloxifene, calcitonin, teriparatide); the index date was the first pharmacy claim. There were three study periods: baseline (12 months pre-index); compliance period (0-12 months post-index); and follow-up period (12-24 months post-index). Medication possession ratio (MPR) was calculated during the compliance period to differentiate two cohorts: compliant (MPR ≥ 80%) and noncompliant (MPR < 80%). Outcomes during follow-up were modeled by logistic regression (presence of fracture), Poisson regression (healthcare utilization incidence rate) and gamma regression (healthcare costs), all adjusted for patient demographic and clinical characteristics. RESULTS: Overall, 685,505 women initiating OP therapy were identified and 57,913 (8.4%) met the inclusion criteria: only 23,430 (40.5%) were compliant and 34,483 (59.5%) were noncompliant. Mean age was 64 years. Noncompliance was associated with a 20% higher risk of any fracture (odds ratio: 1.20, 95% CI = 1.07-1.35), a higher incidence rate ratio (IRR) for inpatient utilization (IRR: 1.26, 95% CI = 1.19-1.34) and a lower rate of outpatient utilization (IRR: 0.97, 95% CI = 0.95-0.98). Noncompliant patients had 13% higher medical costs (cost ratio: 1.13, 95% CI = 1.06-1.21) than compliant patients. LIMITATIONS: Inclusion in this study required 36 months of continuous healthcare coverage. Thus, the results are primarily applicable to a stable, managed care population and may not be generalizable to other populations. CONCLUSION: Noncompliance with OP therapy was associated with a higher risk of fracture, higher all-cause medical costs and a higher frequency of inpatient service utilization. Additional research is needed to identify barriers to compliance with OP therapy.

Osteoporotic fracture rate among women with at least 1 year of adherence to osteoporosis treatment.

PURPOSE: In clinical trials, bisphosphonate therapy reduces but does not eliminate the risk of fracture. The objective of this retrospective observational study was to examine fracture rates among women who were adherent to bisphosphonate therapy for at least 1 year. METHODS: We studied outcomes for women ≥50 years old who received their first osteoporosis therapy as an oral bisphosphonate during 2002-2008 and were enrolled in a large claims database for ≥3 consecutive years, including a baseline year before and 2 years after the index prescription (thus, the full study period was 2001-2010). Adherence during the first year of therapy was defined as a medication possession ratio (MPR) ≥80% (total number of days' supply/365 days × 100%). RESULTS: Of the 62,446 women who met the eligibility criteria, 26,852 (43%) had an MPR ≥80% for osteoporosis therapy during year 1. In year 2, the fracture rate was 52/1000 patient-years. Fragility fractures were recorded for 1292 patients (4.8%) during the baseline year (before initiating therapy); for 1051 patients (3.9%) during year 1 (adherence year); and for 871 patients (3.2%) during year 2. Significant predictors of fracture in year 2 were older age, higher comorbidity score, comorbid inflammatory joint disease, and prior fragility fracture during the baseline year or first year of treatment. The primary limitation of these results is the scope of the claims database, which did not provide information on bone mineral density, supplemental use of calcium or vitamin D, or reasons for initiating oral bisphosphonates. CONCLUSIONS: Despite being adherent to bisphosphonate treatment for 1 year, 3.2% of women experienced a fracture in the subsequent year. These results suggest an unmet need in patients with osteoporosis and an opportunity for newer therapies to help address this need.

Substantial under-treatment among women diagnosed with osteoporosis in a US managed-care population: a retrospective analysis.

BACKGROUND: Multiple therapies are approved for the treatment of osteoporosis (OP), but many patients with osteoporosis may not initiate treatment upon osteoporosis diagnosis. OBJECTIVE: To characterize initiation of pharmacologic OP treatment among women within 1 year of OP diagnosis in a US managed care population. RESEARCH DESIGN AND METHODS: The retrospective cohort study included women aged ≥55 years with a claims-documented diagnosis of OP who were naïve to OP medications prior to OP diagnosis (index date) during 2001-2010. Continuous enrollment for 12 months before (baseline) and after (follow-up) the index date was required. Patients who received OP medications but did not have an OP diagnosis were excluded. Differences in baseline characteristics between the treated and untreated cohorts were compared using Wilcoxon rank-sum (continuous variables) and chi-square tests (categorical variables). MAIN OUTCOMES MEASURES: During the follow-up period, the percentages of patients treated with bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid) and non-bisphosphonates (calcitonin, raloxifene, teriparatide) were determined. RESULTS: A total of 65,344 patients, mean age 65.7 years, met study inclusion exclusion criteria. During the follow-up period, 42,033 patients (64.3%) received no OP medication and 23,311 patients (35.7%) received OP treatment. A total of 20,200 patients (30.9% of total study population) received bisphosphonates and 3111 (4.8% of total) patients received non-bisphosphonates as their index medication. At baseline, untreated patients were slightly older and had higher rates of hypertension, chronic inflammatory joint disease, diabetes mellitus, and gastrointestinal events (p ≤ 0.01) compared with treated patients. CONCLUSIONS: Among women aged ≥55 years in a US managed-care population, 64.3% received no pharmacologic treatment within 1 year after being diagnosed with OP. The authors were not able to determine if untreated patients did not receive or did not fill a prescription. Further research is needed to understand the barriers to OP treatment and reasons for non-treatment.

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.

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.

Development of a practical screening tool to predict low muscle mass using NHANES 1999-2004.

BACKGROUND: Skeletal muscle mass declines after the age of 50. Loss of skeletal muscle mass is associated with increased morbidity and mortality. OBJECTIVE: This study aims to identify predictors of low skeletal muscle mass in older adults toward development of a practical clinical assessment tool for use by clinicians to identify patients requiring dual-energy X-ray absorptiometry (DXA) screening for muscle mass. METHODS: Data were drawn from the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2004. Appendicular skeletal mass (ASM) was calculated based on DXA scans. Skeletal muscle mass index (SMI) was defined as the ratio of ASM divided by height in square centimeters. Elderly participants were classified as having low muscle mass if the SMI was 1 standard deviation (SD) below the mean SMI of young adults (20-40 years old). Logistic regression was conducted separately in males and females age ≥65 years of age to examine the relationship between patients identified as having low muscle mass and health behavior characteristics, adjusting for comorbid conditions. The model was validated on a separate sample of 200 patients. RESULTS: Among the NHANES study population, 551 (39.7 %) males and 374 (27.5 %) females had a SMI below the 1 SD cutoff point. NHANES study subjects with a low SMI were older (mean age, 76.2 vs. 72.7 for male; 76.0 vs. 73.7 for female; and both p < 0.0001) and had a lower body mass index (mean BMI, 24.1 vs. 29.4 for male; 22.9 vs. 29.7 for female; p < 0.0001). In adjusted logistic regression analyses, age (for males) and BMI (for both males and females) remained statistically significant. A parsimonious logistic regression model adjusting for age and BMI only had a C statistic of 0.89 for both males and females. The discriminatory power of the parsimonious model increased to 0.93 for males and 0.95 for females when the cutoff defining low SMI was set to 2 SD below the SMI of young adults. In the validation sample, the sensitivity was 81.6 % for males and 90.6 % for females. The specificity was 66.2 % for males and females. CONCLUSIONS: BMI was strongly associated with a low SMI and may be an informative predictor in the primary care setting. The predictive model worked well in a validation sample.