Health care resource use and costs associated with possible side effects of high oral corticosteroid use in asthma: a claims-based analysis.

BACKGROUND: The objective of this study was to estimate the prevalence of possible oral corticosteroid (OCS)-related side effects and health care resource use and costs in patients with asthma. METHODS: This was a cross-sectional, matched-cohort, retrospective study using a commercial claims database. Adults with asthma diagnosis codes and evidence of asthma medication use were studied. Patients with high OCS use (≥30 days of OCS annually) were divided into those who did versus those who did not experience OCS-related possible side effects. Their health care resource use and costs were compared using linear regression or negative binomial regression models, adjusting for age, sex, geographic region, Charlson Comorbidity Index score, and chronic obstructive pulmonary disease status. RESULTS: After adjustment, high OCS users with possible side effects were more likely to have office visits (23.0 vs 19.6; P<0.001) and hospitalizations (0.44 vs 0.22; P<0.001) than those without possible side effects. Emergency department visits were similar between the groups. High OCS users with possible side effects had higher adjusted total annual mean health care costs ($25,168) than those without such side effects ($21,882; P=0.009). CONCLUSION: Among high OCS users, patients with possible OCS-related side effects are more likely to use health care services than those without such side effects. Although OCS may help control asthma and manage exacerbations, OCS side effects may result in additional health care resource use and costs, highlighting the need for OCS-sparing asthma therapies.

Using administrative claims data to estimate virologic failure rates among human immunodeficiency virus-infected patients with antiretroviral regimen switches.

OBJECTIVE: To develop and validate a claims signature model that estimates proportions of HIV-infected patients in administrative claims databases who switched combination antiretroviral therapy (cART) regimens because of virologic failure. METHODS: The authors used an HIV-specific registry (development data set) to develop logistic regression models to estimate odds of virologic failure among patients who switched cART regimens. Models were validated in a sample of administrative claims with laboratory values (validation data set). The final model was applied to an application data set as a worked example. RESULTS: There were 1691, 1073, and 3954 eligible patients with cART switches in the development, validation, and application data sets, respectively. In the development data set, virologic failure before a switch was observed 21.8% of the time. Failure more likely caused the regimen switch among patients who were treatment experienced, had been receiving their baseline regimen for > 180 days, had ≥ 2 or more physician visits within 90 days, had > 1 HIV RNA or CD4 cell count test within 30 days, had any resistance test within 180 days, or had a change in regimen type. The final model had good discriminatory ability (C = 0.885) and fit (Hosmer-Lemeshow P = 0.8692). Failure was estimated to occur in 18.9% (v. 18.6% observed) of switches in the validation data set and 13.8% in the application data set. CONCLUSIONS: This claims signature model allows payers to use claims data to estimate virologic failure rates in their patient populations, thereby better understanding plan costs of failure.

Cost-effectiveness of 21-gene assay in node-positive, early-stage breast cancer.

OBJECTIVE: To assess impact on health outcomes and healthcare expenditures of adopting a 21-gene assay for women with early-stage, minimally node-positive, estrogen receptor-positive (N (1-3)/ER) HER2-negative breast cancer. STUDY DESIGN: We adapted a deterministic decision-analytic model to estimate costs and quality-of-life outcomes associated with chemotherapy, adverse events, supportive care, recurrence, and second primary cancers for usual care compared with care determined by the 21-gene assay recurrence score, where 71% and 54% of women, respectively, were treated with adjuvant chemotherapy. Model input data were based on national statistics, published literature, physician surveys, and Medicare Part B prices. METHODS: Annual numbers of events were multiplied by quality-adjusted life-years (QALYs) lost and costs to estimate net health and economic impacts of each strategy. Analyses were from a managed care payer perspective for the US population. RESULTS: Patients receiving the assay were predicted to gain 0.127 QALY and save $4359 annually from avoiding chemotherapy, adverse events, supportive care, and secondary primary tumors. For a 2-million member plan, net gains were 4.44 QALYs/year and savings were $13,476/year. Cost savings were greater for the Medicare population. Although overall results were sensitive only to reduced impact of testing and chemotherapy costs, they were still highly cost-effective (incremental cost-effectiveness ratio <$20,000/QALY). CONCLUSIONS: Use of a 21-gene assay in patients with early-stage N (1-3)/ER HER2-negative breast cancer may improve health outcomes and add no incremental cost, thereby providing valuable insight for health plans, the Centers for Medicare and Medicaid Services, and clinicians regarding coverage policies and treatment decisions.

Cost effectiveness of atazanavir-ritonavir versus lopinavir-ritonavir in treatment-naïve human immunodeficiency virus-infected patients in the United States.

OBJECTIVE: To evaluate lifetime cost effectiveness of atazanavir-ritonavir (ATV + r) versus lopinavir-ritonavir (LPV/r), both with tenofovir-emtricitabine, in US HIV-infected patients initiating first-line antiretroviral therapy. METHODS: A Markov microsimulation model was developed to calculate quality-adjusted life-years (QALYs) based on CD4 and HIV RNA levels, coronary heart disease (CHD), AIDS, opportunistic infections (OIs), diarrhea, and hyperbilirubinemia. A million-member cohort of HIV-1-infected, treatment-naïve adults progressed at 3-month intervals through eight health states. Baseline characteristics, virologic suppression, cholesterol changes, and diarrhea and hyperbilirubinemia rates were based on 96-week CASTLE trial results. HIV mortality, OI rates, adherence, costs, utilities, and CHD risk were from literature and experts. LIMITATIONS: The incremental cost-effectiveness ratio (ICER) may be overestimated because the ATV + r treatment effect was based on an intention-to-treat analysis. The QALY weights used for diarrhea, hyperbilirubinemia, and CHD events are uncertain; however, the ICER remained < $50,000/QALY when these values were varied in sensitivity analyses. RESULTS: ATV + r patients received first-line therapy longer than LPV/r patients (97.3 vs. 70.7 months), had longer quality-adjusted survival (11.02 vs. 10.76 years), similar overall survival (18.52 vs. 18.51 years), and higher costs ($275,986 vs. 269,160). ATV+r [corrected] patients had lower rates of AIDS (19.08 vs. 20.05 cases/1000 patient-years), OIs (0.44 vs.0.52), diarrhea (1.27 vs. 6.26), and CHD events(5.44 vs. 5.51), but higher hyperbilirubinemia rates (6.99 vs. 0.25. ATV + r added 0.26 QALYs at a cost of $6826, for $26,421/QALY. CONCLUSIONS: By more effectively reducing viral load with less gastrointestinal toxicity and a better lipid profile, ATV + r lowered rates of AIDS and CHD, increased quality-adjusted survival, and was cost effective (< $50,000/QALY) compared with LPV/r.

Poor disease control among insured users of high-dose combination therapy for asthma.

Adherence to asthma treatment may not completely prevent exacerbations. Clinical trial results indicate that many highly adherent asthma patients still have symptoms. Little is known about the level of control achieved by adherent patients outside clinical trials. This study was designed to evaluate the extent of asthma control among insured patients who were highly adherent to combination controller therapy. We used an administrative claims database for this cohort study of patients aged 12-64 years. Patients were newly treated with fluticasone, 500 micrograms/salmeterol, 50 micrograms, between January 1, 2003 and June 30, 2004. Patients were stratified according to adherence levels: low (<50%), moderate (50-74%), and high (> or =75%). We compared rates of poor control. A logistic regression model was used to control for baseline differences. Among 3357 patients, the mean age was 40.5 +/- 13.6 years, and 64.1% were women. Sixty-one percent had low adherence, 20% had moderate adherence, and 19% had high adherence. Highly adherent patients were older, and more used fluticasone, 250 micrograms/salmeterol, 50 micrograms, during the preindex period than the other groups. Even after starting high-dose fluticasone/salmeterol, many patients with low, moderate, and high adherence had indicators of poor symptom control (28.9% [587/2030], 30.6% [209/682], and 30.7% [198/645], respectively). Patients who were highly adherent and used additional controller medications had rates of poor control that ranged from 23.1 to 31.2%. After adjusting for age, gender, and baseline characteristics, results were similar. Many patients continue to have poor asthma control despite being adherent to high-dose combination therapy or using additional controller medications.

Care of asthma patients in relation to guidelines.

Clinical asthma care may have to change to be brought in line with Expert Panel Report 3 (EPR3) guidelines, which recommend increased intensity of therapy (steps) to treat uncontrolled asthma. This study determined if asthma therapy steps can be identified using claims data and if patients have appropriate step-up in therapy if their disease is not controlled. A cohort study was performed using an administrative claims database and involving patients 12-64 years old with uncontrolled asthma events (either impairment or risk). Patients were assigned to a preindex step (6 months before the index date) and postindex steps (1 year after the index date). The primary study outcome was a change in therapy steps. We used logistic regression to identify variables predictive of an increase in step. Our algorithm for assigning steps appeared internally valid; patients identified as being at higher steps saw more specialists and had higher levels of asthma risk. Among 14,781 patients for which a step-up option existed, 12.4-41.3% had a step-up in therapy after an uncontrolled asthma event. For all steps, high-risk patients had higher odds of having a step-up in therapy than low-risk patients. The odds ratio for appropriate therapy increased with increasing baseline step: from 1.50 for step 2 versus step 1, to 11.41 for step 5 versus step 1. Steps can be assigned using claims data. Bringing care in line with EPR3 guidelines will require significant changes from current practice but will improve quality by reducing use of oral corticosteroids and increasing use of inhaled steroids.

Adherence and persistence with omalizumab and fluticasone/salmeterol within a managed care population.

Asthma control requires adherence with pharmacologic therapy. A medication's mode of delivery may affect adherence. The purpose of this study was to compare medication persistence and adherence between patients newly treated with either an inhaled or injected asthma medication. Using a propensity-score-matched retrospective cohort study, we evaluated medication persistence and adherence over 1 year in adult asthma patients newly treated with omalizumab or fluticasone (500 microg)/salmeterol (50 microg) (FSC 500/50). Kaplan-Meier analysis was conducted to compare persistence between users of FSC 500/50 and omalizumab using the log-rank test. We conducted four sensitivity analyses. After propensity matching, the study sample included 213 omalizumab patients and 426 FSC 500/50 patients, with no statistically significant differences between groups on baseline measures. Mean adherence rates were 64.6% for omalizumab and 29.5% for FSC 500/50 (p < 0.0001). Fifty-four percent of omalizumab users were persistent at 1 year compared with 18.5% of FSC 500/50 users (p < 0.0001). In sensitivity analyses, we stratified patients by evidence of allergy and the results did not change. Adherence was more than twice as high and persistence was almost twice as high among omalizumab compared with FSC 500/50 users. The direction of our findings was consistent across all sensitivity analyses. In both omalizumab and FSC 500/50 cohorts, persistence decreased substantially over 1 year. Our study suggests that injected medications may have advantages in asthma treatment. A comprehensive program to improve adherence should address not just administration route but also patient factors that prevent proper medication use.

The effect of medication adherence on health care utilization in bipolar disorder.

A retrospective analysis of electronic prescription and medical claims representing approximately 1.4 million managed care commercial health plan members with mental health benefits was conducted. The effect of patient adherence to traditional mood-stabilizer therapy (lithium, valproate, carbamazepine, lamotrigine, or oxcarbazepine) for bipolar disorder on mental health-related hospitalization was assessed among 1,399 patients (mean age, 42.9 yr; 66.3% female) studied. Reduced adherence to traditional mood-stabilizing therapy (< 80%) in patients with bipolar disorder was associated with significantly greater risk of mental health-related, emergency room visits (odds ratio, 1.98; 95% confidence interval, 1.38-2.84) and inpatient hospitalizations (odds ratio, 1.71; 95% confidence interval, 1.27-2.32), even after adjusting for age, gender, and comorbidity.

Gastrointestinal bleeding rates among managed care patients newly started on cox-2 inhibitors or nonselective NSAIDs.

OBJECTIVE: While cyclooxygenase-2 (COX-2) inhibitors were introduced to the U.S. market with the promise of less gastrointestinal (GI) toxicity than nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), additional research is needed to examine this outcome in the naturalistic setting. The objective of this study was to examine whether use of COX-2 inhibitors is associated with reduced risk of GI bleed in a managed care population. METHODS: Adult patients in a multistate managed care organization that were initiated on a nonselective NSAID between January 1999 and August 2002 were identified and matched using propensity scoring with patients in the same managed care organization that were initiated on a COX-2 inhibitor. Matching variables included age, gender, geographical state, comorbidity index, corticosteroid use, warfarin use, arthritis indication, and history of recent GI bleed. Patients were followed until they switched or discontinued their NSAID or COX-2 inhibitor, disenrolled from the health plan, developed a GI bleed, or reached the end of the 1-year follow-up period. A GI bleed was defined as an inpatient hospitalization for GI bleed or at least 2 medical claims with a primary diagnosis for GI bleed. The relative risk (RR) of GI bleed was calculated using proportional hazards regression. RESULTS: Overall, 35,007 pairs of COX-2 inhibitor and nonselective NSAID users were evaluated. Mean age was 63 years, and 65% were female. There were 375 cases of GI bleed among 19,201 follow-up years for COX-2 users (19.5 cases per 1,000 person-years) versus 228 cases of GI bleed among 12,680 follow-up years for NSAID users (18.0 cases per 1,000 person-years). The risk of GI bleed was not significantly different for COX-2 users compared with nonselective NSAID users (RR 1.07; 95% confidence interval [CI], 0.90-1.26). Even among high-risk patients, there was no reduction in the risk of a GI bleed among users of COX-2 inhibitors (RR 0.995; 95% CI, 0.84 -1.19). CONCLUSION: Overall, within this managed care population, COX-2 inhibitor users did not have a reduced risk of a GI bleed compared with patients with similar baseline characteristics using nonselective NSAIDs.

Comparison of costs and utilization between users of insulin lispro versus users of regular insulin in a managed care setting.

OBJECTIVE: To compare medical and pharmacy costs and utilization between patients with diabetes who received insulin lispro versus regular human insulin. METHODS: A retrospective analysis of medical and pharmacy claims was conducted among continuously enrolled users of insulin lispro or regular insulin during the identification period, March 1, 2000, through February 28, 2001, within a large managed care organization. This study improved upon the methodology used in previous studies by (a) stratifying (rather than 1:1 matching) individuals by their likelihood to use insulin lispro using the propensity score binning technique, and (b) refining the study inclusion criteria to include only patients with 3 or more fills of the insulin under study (lispro or regular) to exclude individuals who may have been on either product for a short time. Because the propensity score binning technique groups patients with similar baseline characteristics within strata (bins) and not among individual patients, almost the entire available sample is retained in the analysis, unlike propensity score matching, where large numbers of patients can be excluded depending on the matching scheme. Therefore, the propensity score binning technique, because it uses more complete information, is less likely to produce biased results. Patients were grouped into 5 bins (quintiles) based on their estimated likelihood to receive insulin lispro rather than regular insulin. The propensity score model used baseline characteristics of age, gender, comorbidities, use of oral antidiabetic medications, prescription copayment, and diabetes-related costs and utilization. Overall cost and utilization differences (lispro minus regular insulin) during the 12-month follow-up period were calculated using weights inversely proportional to variances of within-bin differences. RESULTS: Of 6,436 patients, 1,972 (30.6%) received insulin lispro and 4,464 (69.4%) received regular insulin. The propensity score estimation produced 5 bins, each containing between 1,287 and 1,288 patients, utilizing all patients in the analysis. Patients in the lower-numbered propensity score quintiles were older, more likely to use oral antidiabetic medications, and had more comorbidities than those in the higher-numbered quintiles. As quintile number increased, the percentage of insulin lispro users also increased. The weighted mean annual cost difference (lispro minus regular insulin) per patient was + USD 79 (P < 0.001) for diabetes-related pharmacy cost, + USD 212 (P < 0.001) for total pharmacy cost, USD 75 (P < 0.857) for diabetes-related medical cost, USD 2,286 (P <0.011) for nondiabetes medical cost, and USD 2,327 (P = 0.072) for total medical cost. CONCLUSIONS: Compared with regular insulin users, insulin lispro users incurred higher diabetes-related and total pharmacy costs but lower nondiabetes medical costs and similar total medical costs. Fewer hospitalizations among insulin lispro as compared with regular insulin users contributed to lower nondiabetes medical costs and similar total medical costs.