Ankita Modi

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

Abstract 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.

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

Abstract 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.

Challenges in implementing and maintaining osteoporosis therapy.

In the United States, an estimated 19% of older men and 30% of older women are at elevated risk of osteoporotic fracture and considered to be eligible for treatment. The burden of osteoporosis is similar in Europe and is projected to rise worldwide, with aging populations and increasing fracture rates accompanying urbanization. Notwithstanding its high prevalence, osteoporosis is often underdiagnosed and undertreated. Moreover, even when the diagnosis is made and the decision is taken to treat, there are remaining challenges in implementing therapy for osteoporosis. Several patient populations are particularly challenging for clinicians to treat and require further study with regard to osteoporosis therapy. These include the very elderly, who face challenges relating to adherence; men, in whom osteoporosis remains under-recognized; patients with glucocorticoid-induced osteoporosis or renal impairment, who are at increased risk of fracture; patients with preexisting gastrointestinal problems who cannot tolerate existing orally administered osteoporosis therapies; and high-risk patients who show inadequate response to therapy. Moreover, poor adherence and poor persistence with osteoporosis medications are common and result in an increased risk of fracture, higher medical costs, and increased hospitalizations. Once the decision to institute therapy is made, patient education about osteoporosis and fracture risk should be provided. This is particularly important for men, who may not be aware that osteoporosis can be a concern. Secondary prevention programs, including fracture liaison services and bone therapy groups, can help to improve adherence to therapy. Further study is needed to guide the treatment of men, the very elderly, patients with glucocorticoid-induced osteoporosis and renal impairment, high-risk patients not well-controlled despite therapy, and patients with preexisting gastrointestinal conditions. Moreover, therapies are needed that are viewed as effective and safe by both physicians and patients, and as convenient to take by patients.

Proportion of osteoporotic women remaining at risk for fracture despite adherence to oral bisphosphonates.

BACKGROUND Adherence to oral bisphosphonates is often low, but even adherent patients may remain at elevated fracture risk. The goal of this study was to estimate the proportion of bisphosphonate-adherent women remaining at high risk of fracture. METHODS A retrospective cohort of women aged 50years and older, adherent to oral bisphosphonates for at least two years was identified, and data were extracted from a multi-system health information exchange. Adherence was defined as having a dispensed medication possession ratio≥0.8. The primary outcome was clinical occurrence of: low trauma fracture (months 7-36), persistent T-score≤-2.5 (months 13-36), decrease in bone mineral density (BMD) at any skeletal site≥5%, or the composite of any one of these outcomes. RESULTS Of 7435 adherent women, 3110 had either pre- or post-adherent DXA data. In the full cohort, 7% had an incident osteoporotic fracture. In 601 women having both pre- and post-adherent DXA to evaluate BMD change, 6% had fractures, 22% had a post-treatment T-score≤-2.5, and 16% had BMD decrease by ≥5%. The composite outcomes occurred in 35%. Incident fracture was predicted by age, previous fracture, and a variety of co-morbidities, but not by race, glucocorticoid treatment or type of bisphosphonate. CONCLUSION Despite bisphosphonate adherence, 7% had incident osteoporotic fractures and 35% had either fracture, decreases in BMD, or persistent osteoporotic BMD, representing a substantial proportion of treated patients in clinical practices remaining at risk for future fractures. Further studies are required to determine the best achievable goals for osteoporosis therapy, and which patients would benefit from alternate therapies.

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

Abstract 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.

Cost and Consequences of Nonadherence With Oral Bisphosphonate Therapy Findings From a Real-World Data Analysis

Background: Adherence to osteoporosis treatment remains poor despite available treatments and physician and patient education. This study aims to determine the effect of low adherence in real-world data. Objective: To examine the association between adherence with oral bisphosphonate therapy and fracture risk as well as health care resource utilization. Methods: Women included in this retrospective analysis were 55 years or older and had started oral bisphosphonate therapy between 2005 and 2011 in a large not-for-profit health care center in Israel. Adherence to therapy was measured by the medication possession ratio (MPR) during the first year from therapy initiation. Patients with MPR lower than 70% were considered nonadherent. Study outcomes were osteoporotic fracture events and health care utilization (including physician visits and hospitalizations) during the second year from therapy initiation. Results: Among the 17 770 women included in the analysis (mean age = 66.5 years; SD = ±8.3 years), 48.9% were nonadherent to therapy during the first year of treatment. Osteoporotic fracture risks during the second year among adherent and nonadherent patients were 2.1% and 2.5%, respectively (P = 0.1). When analysis was limited to patients 75 years or older, nonadherence with bisphosphonates was associated with an adjusted odds ratio of 1.49 (95% CI = 1.08-2.04) for osteoporotic fractures compared with adherent patients. Nonadherent patients had 13.4% higher medical costs than their adherent counterparts among patients 75 years and older (P = 0.002). Conclusions: In patients 75 years and older, nonadherence with oral bisphosphonates can be associated with significantly greater short-term risk of osteoporotic fractures and higher utilization of health care services.

Association of gastrointestinal events and osteoporosis treatment initiation in newly diagnosed osteoporotic Israeli women

The objective was to examine the association of gastrointestinal (GI) events and osteoporosis treatment initiation patterns among postmenopausal women following an osteoporosis diagnosis from an Israeli health plan.

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.

Gastrointestinal Events Among Patients Initiating Osteoporosis Therapy: A Retrospective Administrative Claims Database Analysis

PURPOSE Our purpose was to characterize the occurrence of gastrointestinal (GI) events among women on oral bisphosphonate therapy. METHODS This was a retrospective cohort study that used a United States (US) claims database. The study period was from January 1, 2000, to December 31, 2011. The index date was the date of the first oral bisphosphonate (alendronate, ibandronate, or risedronate) prescription and occurred between January 1, 2001, and December 31, 2010. The pre- and post-index periods were the 1-year periods before and after the index date, respectively. The analysis included women with osteoporosis aged ≥55 years at the index date who were naive to all osteoporosis treatments before the index date and were continuously enrolled in the health plan for at least 1 year before and 1 year after the index date. Patients with a diagnosis of malignant neoplasm during the pre- or post-index periods or a diagnosis of Paget disease anytime in the claims history were excluded. The occurrence of GI events (defined as esophagitis; gastroesophageal reflux disease; ulcer, stricture, perforation, or hemorrhage of the esophagus; gastric, duodenal, or peptic ulcer; acute gastritis; duodenitis; GI hemorrhage; nausea/vomiting; or dysphagia) was assessed during the pre-index period and at 3, 6, and 12 months in the post-index period. The rate of GI events was defined as the percentage of patients having at least 1 GI event in each analysis period (ie, pre-index and post-index periods). GI events in the post-index period were also stratified by the presence of GI events in the pre-index period. FINDINGS A total of 75,593 women were included in the analysis. The average age at the index date was 64.4 years. Gastroprotective agents were used by 17.9% of patients. Approximately one fourth of patients (26.6%; n = 20,073) had ≥1 GI events in the pre-index period. Approximately the same proportion of patients (28.0%; n = 21,142) experienced GI events in the post-index period. The cumulative rate of GI events during the post-index period was higher among patients who had GI events in the pre-index period (51.2%) than among patients without a GI event in the pre-index period (19.6%). IMPLICATIONS Among women with osteoporosis enrolled in a US commercial plan, GI events were common regardless of bisphosphonate use. Approximately one fourth of US women on bisphosphonate therapy experienced GI events within the year after initiation of therapy, and one half of US women with a previous GI event had another event while taking bisphosphonates.

Undertreatment of osteoporosis and the role of gastrointestinal events among elderly osteoporotic women with Medicare Part D drug coverage

Objectives To examine the rate of osteoporosis (OP) undertreatment and the association between gastrointestinal (GI) events and OP treatment initiation among elderly osteoporotic women with Medicare Part D drug coverage. Methods This retrospective cohort study utilized a 20% random sample of Medicare beneficiaries. Included were women ≥66 years old with Medicare Part D drug coverage, newly diagnosed with OP in 2007–2008 (first diagnosis date as the index date), and with no prior OP treatment. GI event was defined as a diagnosis or procedure for a GI condition between OP diagnosis and treatment initiation or at the end of a 12-month follow-up, whichever occurred first. OP treatment initiation was defined as the use of any bisphosphonate (BIS) or non-BIS within 1 year postindex. Logistic regression, adjusted for patient characteristics, was used to model the association between 1) GI events and OP treatment initiation (treated versus nontreated); and 2) GI events and type of initial therapy (BIS versus non-BIS) among treated patients only. Results A total of 126,188 women met the inclusion criteria: 72.1% did not receive OP medication within 1 year of diagnosis and 27.9% had GI events. Patients with a GI event were 75.7% less likely to start OP treatment (odds ratio [OR]=0.243; P<0.001); among treated patients, patients with a GI event had 11.3% lower odds of starting with BIS versus non-BIS (OR=0.887; P<0.001). Conclusion Among elderly women newly diagnosed with OP, only 28% initiated OP treatment. GI events were associated with a higher likelihood of not being treated and, among treated patients, a lower likelihood of being treated with BIS versus non-BIS.