Budgetary impact of the utilization of buprenorphine/naloxone sublingual film and tablet for Medicaid in the United States

Abstract

Objectives:

The buprenorphine/naloxone combination for the treatment of opioid dependence is available in a film or tablet formulation. Recent retrospective studies demonstrated that treatment with the sublingual film formulation is associated with improved treatment retention and lower healthcare costs. In March 2013, generic buprenorphine/naloxone tablets were approved in the US. A budget impact model was built to compare healthcare expenditures for different market shares of sublingual film and tablet.     

Clinical and economic outcomes in patients with type 2 diabetes initiating insulin glargine disposable pen versus exenatide BID

Abstract

Objective:

To evaluate clinical and economic outcomes in patients with type 2 diabetes mellitus (T2DM) who failed oral anti-diabetic drug (OAD) therapy and initiated either insulin glargine with disposable pen (GLA-P) or exenatide BID (EXE).

Research design and methods:

This retrospective study used data from a large US-managed care claims database and included adult T2DM patients initiating treatment with GLA-P or EXE in 2007 or 2008. Propensity score matching was used to control observed baseline differences between treatment groups. Primary study end-points included treatment persistence, A1C, healthcare utilization, and healthcare costs during the 1-year follow-up period.

Results:

Two thousand three hundred and thirty nine patients were included in the study (GLA-P: 381; EXE: 1958); 626 patients were in the 1:1 matched cohort (54% male; mean age: 54 years; mean A1C: 9.2%). At follow-up, patients in the GLA-P group were significantly more persistent in treatment than EXE patients (48% vs 15% in persistence rate and 252 vs 144 days in persistence days; both p?<?0.001). GLA-P patients also had significantly lower A1C at follow-up (8.02% vs 8.32%; p?=?0.042) and greater A1C reduction from baseline (?1.23% vs ?0.92%; p?=?0.038). There were no significant differences in claims-based hypoglycemia rates and overall diabetes-related healthcare utilization and cost.

Limitations:

Since this was a retrospective analysis, causality of treatment benefits cannot be established. The study was specific to two treatments and may not generalize to other models of insulin administration. Some of the results, although statistically significant, may not be found clinically important.

Conclusions:

In a real-world setting among T2DM patients who failed to achieve or sustain glycemic goal with OADs, initiation of GLA-P instead of EXE may be a more effective option because it was associated with greater treatment persistence, greater A1C reduction without a significantly higher rate of hypoglycemia, and similar healthcare costs.     

Healthcare costs associated with bevacizumab and cetuximab in second-line treatment of metastatic colorectal cancer

Abstract

Objective:

To compare the health care costs of patients with metastatic colorectal cancer (mCRC) who received second-line treatment with Avastin (bevacizumab) versus Erbitux (cetuximab), from the third-party payer’s perspective.

Methods:

Patients with mCRC were selected from the PharMetrics claims database if they received second-line therapy containing either bevacizumab (second-line bevacizumab cohort) or cetuximab (second-line cetuximab cohort). Six-month costs following second-line therapy start date and average monthly healthcare costs while on second-line therapy (in 2009 US$) were calculated and compared between the two groups.

Results:

A total of 2188 patients with mCRC who met the eligibility criteria were included in the analysis, including 1808 patients receiving bevacizumab and 380 patients receiving cetuximab in second-line treatment. Demographic and baseline characteristics were similar between the two groups. Patients’ mean age was 61 years and 56% were males. In second-line treatment, bevacizumab was commonly used with oxaliplatin (43.5%) and irinotecan-based regimens (40.4%), whereas cetuximab was commonly used with irinotecan-based regimens (68.2%). Bevacizumab patients had significantly lower total all-cause healthcare costs than cetuximab patients (adjusted difference: –$10,231, p?=?0.020), and lower medical costs (–$10,796, p?=?0.012) during the 6 months following second-line therapy initiation. Approximately half of the difference in total all-cause healthcare costs was attributable to the lower chemotherapy and targeted therapy costs (–$5635, p?=?0.032) of bevacizumab patients than those of cetuximab patients. While on second-line therapy, bevacizumab patients also had lower average monthly all-cause healthcare costs than cetuximab patients.

Limitations:

Second-line treatment in the current study was defined based on changes in mCRC medications, not based on disease progression due to the limited clinical information available in claims.

Conclusion:

The use of bevacizumab in second-line therapy was associated with significantly lower healthcare costs in mCRC patients, compared to the use of cetuximab.     

Real-world rates,predictors, and associated costs of hypoglycemia among patients with type 2 diabetes mellitus treated with insulin glargine: results of a pooled analysis of six retrospective observational studies

Abstract

Objective:

To evaluate the real-world rates of hypoglycemia and related costs among patients with type 2 diabetes mellitus (T2DM) who initiated insulin glargine with either a disposable pen or vial-and-syringe.

Methods:

Pooled data were evaluated from six previously published, retrospective, observational studies using US health plan insurance claims databases to investigate adults with T2DM who initiated insulin glargine. The current study evaluated baseline characteristics, hypoglycemic events, and costs during the 6 months prior to and 12 months following insulin glargine initiation. Comparisons were made between patients initiating treatment with a disposable pen (GLA-P) and vial-and-syringe (GLA-V). Multivariate analyses using baseline characteristics as covariates determined predictors of hypoglycemia after initiating insulin glargine.

Results:

This study included 23,098 patients (GLA-P: 14,911; GLA-V: 8187). Overall annual prevalence of hypoglycemia was low (6.3% overall, 2.2% related to hospital admission or emergency department visit). Prevalence was significantly lower with GLA-P (5.5% vs 7.7%; p?<?0.0001). Furthermore, average glycated hemoglobin HbA1c reduction was higher with GLA-P (?1.22% vs ?0.86%; p?=?0.0012). The average annual hypoglycemia-related cost associated with initiating insulin glargine was $293, with GLA-P being 46% lower than GLA-V ($225 vs $417; p?=?0.001). Patients who had already developed microvascular complications at the time of initiating insulin therapy were at higher risk for developing hypoglycemia.

Limitations:

This study is limited by the use of retrospective data and ICD-9-CM codes, which are subject to coding error. In addition, this pooled analysis used unmatched cohorts, with multivariate regression analyses employed to adjust for between-group differences. Finally, results describe a managed care sample and cannot be generalized to all patients with T2DM.

Conclusions:

Patients with T2DM initiating insulin glargine treatment showed low rates of hypoglycemia, especially when using a disposable pen device. Hypoglycemia-related costs were low, contributing a very small proportion to overall diabetes-related healthcare costs.     

Cost-effectiveness of subdermal implantable buprenorphine versus sublingual buprenorphine to treat opioid use disorder

Aims: Subdermal implantable buprenorphine (BSI) was recently approved to treat opioid use disorder (OUD) in clinically-stable adults. In the pivotal clinical trial, BSI was associated with a higher proportion of completely-abstinent patients (85.7% vs 71.9%; p?=?.03) vs sublingual buprenorphine (SL-BPN). Elsewhere, relapse to illicit drug use is associated with diminished treatment outcomes and increased costs. This study evaluated the cost-effectiveness of BSI vs SL-BPN from a US societal perspective.

Methods: A Markov model simulated BSI and SL-BPN cohorts (clinically-stable adults) transiting through four mutually-exclusive health states for 12 months. Cohorts accumulated direct medical costs from drug acquisition/administration; treatment-diversion/abuse; newly-acquired hepatitis-C; emergency room, hospital, and rehabilitation services; and pediatric poisonings. Non-medical costs of criminality, lost wages/work-productivity, and out-of-pocket expenses were also included. Transition probabilities to a relapsed state were derived from the aforementioned trial. Other transition probabilities, costs, and health-state utilities were derived from observational studies and adjusted for trial characteristics. Outcomes included incremental cost per quality-adjusted-life-year (QALY) gained and incremental net-monetary-benefit (INMB). Uncertainty was assessed by univariate and probabilistic sensitivity analysis (PSA).

Results: BSI was associated with lower total costs (?$4,386), more QALYs (+0.031), and favorable INMB at all willingness-to-pay (WTP) thresholds considered. Higher drug acquisition costs for BSI (+$6,492) were outpaced, primarily by reductions in emergency room/hospital utilization (?$8,040) and criminality (?$1,212). BSI was cost-effective in 89% of PSA model replicates, and had a significantly higher NMB at $50,000/QALY ($20,783 vs $15,007; p?Conclusions: BSI was preferred over SL-BPN from a health-economic perspective for treatment of OUD in clinically-stable adults. These findings should be interpreted carefully, due to some relationships having been modeled from inputs derived from multiple sources, and would benefit from comparison with outcomes from studies that employ administrative claims data or a naturalistic comparative design.     

Inflammatory bowel disease: healthcare costs for patients who are adherent or non-adherent with infliximab therapy

Objective:

Healthcare costs of inflammatory bowel disease are substantial. This study examined the effect of adherence versus non-adherence on healthcare costs in patients with inflammatory bowel disease.

Methods:

Adults who started infliximab treatment between 2006 and 2009 and had a diagnosis of inflammatory bowel disease were identified from MarketScan Databases. Medication adherence was defined as an infliximab medication possession ratio of 80% or greater in the first year. Mean treatment effects (adherence versus non-adherence) on costs in adherent patients were estimated with propensity-weighted generalized linear models.

Results:

A total of 1646 patients were identified. Significant variables in the model used to develop propensity weights were age, year of infliximab initiation, having Medicare coverage, presence of supplementary diagnoses, office as the place of service for infliximab initiation, prior aminosalicylate use, prior outpatient costs, number of prior outpatient visits, and number of prior colonoscopies. Mean total costs in adherent (n?=?674) and propensity-weighted non-adherent (n?=?972) patients were $41,713 versus $47,411 overall (p?p?p?p?p?p?=?0.460).

Limitations:

Costs associated with infliximab administration (infusions, adverse events) were captured in healthcare costs (inpatient, outpatient, and emergency room), not in infliximab costs. The influence of adherence on indirect costs (e.g., time lost from work) could not be determined. Reasons for non-adherence were not available in the database.

Conclusions:

In patients who were adherent to infliximab treatment (a medication possession ratio of 80% or greater in the first year), adherence versus non-adherence was associated with lower total healthcare costs, supporting the overall value of infliximab adherence in patients with inflammatory bowel disease.     

Corroboration of claims algorithm for second-line costs of metastatic colorectal cancer treatment with targeted agents

Abstract

Objective:

To refine a claims algorithm for identifying second-line systemic regimens for metastatic colorectal cancer (mCRC) based on clinical evidence and to compare costs during second-line treatment by targeted therapy administered.

Methods:

This retrospective analysis of a large US managed care database identified patients diagnosed with mCRC during 1 July 2007–30 June 2011. A claims-based algorithm was developed to identify patients with at least two lines of therapy (LOT) and the second LOT contained one targeted agent: bevacizumab or any anti-epidermal growth factor receptor (EGFR). Medical chart data from 92 patients were used to corroborate and refine the LOT algorithm. The positive predictive value (PPV) of the initial algorithm and refined algorithm for identification of second LOT are presented. The final algorithm was applied to claims data and two mutually exclusive second-line cohorts were examined: patients with bevacizumab- or cetuximab-containing regimens. Second-line healthcare costs were analyzed with generalized linear models adjusted for demographic and clinical characteristics.

Results:

The PPV increased from 50.0% (95% CI?=?39.4–60.6) for the initial algorithm to 72.1% (95% CI?=?59.2–82.9) for the final algorithm. Mean age in the cohorts (n?=?569) was 61 years; 58% were men. Days of therapy were similar for the bevacizumab (n?=?450) vs cetuximab (n?=?119) cohorts, respectively: 131 vs 148 in first LOT and 123 (both cohorts) in second LOT (p?≥?0.27). Total costs during second-line treatment in the bevacizumab cohort were lower by $12,318 (p?=?0.02) and medical costs were lower by $13,809 (p?=?0.01). Monthly total and medical costs were lower by $2728 (p?=?0.03) and $3133 (p?=?0.01), respectively. Results are based on commercially or Medicare-insured patients and may not be generalizable to Medicaid or uninsured patients.

Conclusions:

Corroboration of claim-based algorithms with medical chart data improved algorithm performance. Second-line total and medical costs were lower for mCRC patients treated with bevacizumab compared with cetuximab.     

Treatment patterns and resource utilization and costs among patients with pulmonary arterial hypertension in the United States

Abstract

Objective:

To explore treatment patterns and resource utilization and cost for subjects with pulmonary arterial hypertension (PAH).

Research design:

Retrospective claims database analysis of 706 patients with PAH enrolled in a large, geographically diverse US managed-care organization.

Results:

In the final sample of PAH patients treated with bosentan (n?=?251) or sildenafil (n?=?455), average age was 57 years, 86% of patients were commercially insured, and 52% of patients were male. Gender distribution varied significantly across subgroups, with a lower proportion of males in the bosentan (30%) subgroup compared with the sildenafil group (64%) (p?<?0.001). Average baseline Charlson comorbidity score was 2.4. Average numbers of fills per month were 0.8 and 0.4 for bosentan and sildenafil patients, respectively (p?<?0.001). Over 80% of patients received only one PAH treatment in the first 90 days following the index date, with 28% of bosentan and 13% of sildenafil patients receiving combination therapy (p?<?0.001). Over one-third of bosentan patients and one-quarter of sildenafil patients experienced a dose increase in the follow-up period (p?=?0.009). Sixteen percent of sildenafil patients experienced a dose decrease in the follow-up period, while a smaller proportion of patients receiving bosentan (4%) experienced a dose decrease (p?<?0.001). On average, number of PAH-related per subject per month (PSPM) inpatient stays and emergency department visits and PSPM length of inpatient stays were statistically similar between the subgroups. PAH-related PSPM healthcare costs were high for both subgroups, with average monthly costs of $5,332 and $3,632 among bosentan and sildenafil patients, respectively (p?=?0.003). Differences in total costs were driven mainly by differences in pharmacy expenditures.

Conclusions:

Of the oral agents approved for treating PAH at the time of this study, sildenafil was most commonly prescribed as index therapy and was also associated with the lowest costs, largely due to significantly lower pharmacy costs. This study is characterized by limitations inherent to claims database analyses, such as the potential for coding errors and lack of information on whether a drug was taken as prescribed. Furthermore, PAH severity (WHO functional class) was not assessed.     

Cost analysis: treatment of chemotherapy-induced anemia with erythropoiesis-stimulating agents in five European countries

Abstract

Objective:

Cost-analysis comparing darbepoetin-alfa (DARB), epoetin-alfa (EPO-A), and epoetin-beta (EPO-B) for treatment of chemotherapy-induced anemia in Belgium concluded that costs for DARB-treated patients were significantly lower than costs for EPO-A- or EPO-B-treated patients. The objective of the present study was to extend the Belgian analysis to Austria, France, Italy, Portugal, and Spain, estimating differences in costs between erythropoiesis-stimulating agents (ESAs) in each country.

Methods:

Differences in epidemiology and treatment patterns between countries were adjusted using data from Eurostat, national cancer registries, IMS sales data, and reimbursement and treatment guidelines. Belgian unit costs were replaced with country-specific costs. Costs were analyzed using a mixed-effects model stratifying for propensity score quintiles.

Results:

All populations were comparable to the Belgian population in terms of age, gender, ESA, and blood transfusions use. After adjusting for country-specific chemotherapy use and cancer incidence, total management costs per patient (Euro, 2010) were 19–26% (France, Spain) lower with DARB compared with EPO-A (p?<?0.0001) and 20–36% (Portugal, Austria) compared with EPO-B (p?<?0.01). Anemia-related costs with DARB were between 12% (Portugal; p?=?0.0235) and 38% (Italy; p?<?0.0001) lower compared with EPO-A (p?<?0.01; all remaining countries), and between 13% (Austria; p?=?0.064) and 19% (Portugal; p?=?0.0028) lower compared with EPO-B (p?<?0.05; all remaining countries except Italy; p?=?0.0935).

Limitations:

Not all differences could be accounted for by a lack of country-specific data; however, the potential under- and over-estimation of costs should be similar for all three ESAs.

Conclusions:

These findings are in line with the Belgian analysis. In all countries, total and anemia-related costs were lowest in patients receiving DARB vs EPO-A or EPO-B. This study demonstrates the feasibility of adapting real-life country-specific data to other settings, adjusting for differences in patients’ characteristics and treatment strategies. These findings should be valuable in healthcare decision-making in oncology patients treated in each of the countries studied.     

Pharmacological control of secondary hyperparathyroidism in hemodialysis subjects: a cost consequences analysis of data from the FARO study

Abstract

Background and objectives:

Secondary hyperparathyroidism (SHPT) is a frequent complication of CKD with incidence, prevalence, and costs increasing worldwide. The objective of this analysis was to estimate therapy cost of SHPT in a sub-population of the FARO study.

Materials and Methods:

In the FARO study, an observational survey aimed to evaluate patterns of treatment in patients with SHPT who had undergone hemodialysis, pharmacological treatments and biochemical parameters evolution data were collected in four surveys. Patients maintaining the same treatment in all sessions were grouped by type of treatment and evaluated for costs from the Italian National Health Service perspective.

Results:

Four cohorts were identified: patients treated with oral (PO) calcitriol (n?=?182), intravenous (IV) calcitriol (n?=?34), IV paricalcitol (n?=?62), and IV paricalcitol?+?cinacalcet therapy (n?=?20); the cinacalcet monotherapy group was not analysed due to low number of patients (n?=?9). Parathyroid hormone (PTH) level at baseline and effectiveness of treatments in suppressing PTH level were assessed to test comparability among cohorts: calcitriol PO patients were significantly less severe than others (PTH level at baseline lower than 300?pg/ml; p?<?0.0001); calcitriol IV patients did not reach significant reduction in PTH level. Paricalcitol and paricalcitol?+?cinacalcet treatment groups results were comparable, while only the IV paricalcitol cohort’s PTH level, weekly dosage, and cost decreased significantly from the first to the fourth survey (p?=?0.020, p?=?0.012, and p?=?0.0124, respectively). Total costs per week of treatment (including calcium-based phosphate binder and sevelamer) were significantly lower in the paricalcitol vs paricalcitol?+?cinacalcet cohort (p?<?0.001). Major limitations of this study are related to the survey design: not controlled and lack of comparability between cohorts; however, reflective of true practice patterns.

Conclusions:

The IV Paricalcitol cohort had significantly lower treatment costs compared with patients treated with paricalcitol?+?calcimemtics (p?<?0.001), without a significant difference in terms of baseline severity and PTH control.     

Respiratory-related medical expenditure and inpatient utilisation among COPD patients receiving long-acting bronchodilator therapy

Abstract

Objective:

To evaluate chronic obstructive pulmonary disease (COPD)-related expenditure and hospitalisation in COPD patients treated with tiotropium versus alternative long-acting bronchodilators (LABDs).

Methods:

Data were from the Thomson Reuters MarketScan Research Databases. COPD patients ≥35 years with at least one LABD claim between July 1, 2004 and June 30, 2006 were classified into five cohorts based on index LABD: monotherapy with tiotropium, salmeterol/fluticasone propionate, formoterol fumarate, or salmeterol or combination therapy. Demographic and clinical characteristics were evaluated for a 6-month pre-period and COPD-related utilisation and total costs were evaluated for a 12-month follow-up period. LABD relationship to COPD-related costs and hospitalisations were estimated by multivariate generalised linear modelling (GLM) and multivariate logistic regression, respectively.

Results:

Of 52,274 patients, 53% (n?=?27,457) were male, 71% (n?=?37,271) were ≥65?years, and three LABD cohorts accounted for over 90% of the sample [53% (n?=?27,654) salmeterol/fluticasone propionate, 23% (n?=?11,762) tiotropium, and 15% (n?=?7755) combination therapy]. Patients treated with salmeterol/fluticasone propionate (p?<?0.001), formoterol fumarate (p?=?0.032), salmeterol (p?=?0.004), or with combination therapy (p?<?0.001) had higher COPD-related costs and a greater risk of inpatient admission (p?<?0.01 for all) versus tiotropium.

Limitations:

These data are based on administrative claims and as such do not include clinical information or information on risk factors, like smoking status, that are relevant to this population.

Conclusions:

Patients treated with tiotropim had lower COPD-related expenditures and risk of hospitalisation than patients treated with other LABDs     

Clinical and economic burden of extra-articular manifestations in ankylosing spondylitis patients treated with anti-tumor necrosis factor agents

Abstract

Objective:

To assess concomitant extra-articular manifestation (EAM) rates in patients with ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (anti-TNF) agents and examine the economic burden of uveitis and inflammatory bowel disease (IBD) in French and German AS patients.

Methods:

Previous analyses of uveitis and IBD in AS patients treated with infliximab, etanercept or adalimumab were identified in PubMed/Medline (January 2000 to August 2011). A supplemental analysis incorporated more recent adalimumab clinical trial data (ATLAS [NCT00085644] and RHAPSODY [NCT00478660]). For resource utilization/costs associated with EAMs, the search was expanded to general spondyloarthritis (SpA) conditions (i.e., AS, reactive or psoriatic arthritis, psoriatic spondylitis, IBD and undifferentiated SpA). Direct and indirect yearly costs associated with AS-associated uveitis and IBD were estimated based on interviews with French and German clinicians and literature review.

Results:

The pooled average rate of anterior uveitis (AU) flares for patients treated with anti-TNF therapy in two meta-analyses and supplemental adalimumab clinical trials was 4.9/100-patient-years (PYs). AU rates (per 100-PYs) were 3.4, 3.7 and 5.7 for infliximab (p?=?0.26 vs etanercept; p?=?0.86 vs adalimumab), adalimumab (p?=?0.033 vs etanercept) and etanercept, respectively. IBD flares (per 100-PYs) were 0.2 for infliximab (p?<?0.001 vs etanercept; p?=?0.18 vs adalimumab), 0.63 for adalimumab (p?=?0.009 vs etanercept) and 2.2 for etanercept. No studies assessing EAM-associated resource utilization or costs in AS patients were found. Direct medical costs associated with IBD treatment ranged from €483 (Germany) to €6443 (France). Clinician-estimated AS-related uveitis direct medical costs were €1410 (Germany) and €1812 (France).

Conclusions:

Clinical data synthesis demonstrated significantly lower AU flare rates with adalimumab vs etanercept and significantly lower IBD rates with both adalimumab and infliximab vs etanercept. Economic analysis indicated substantial costs associated with AU and IBD flares secondary to AS in France and Germany. Future economic evaluations of anti-TNF agents should incorporate EAMs and subsequent treatment costs. Limitations include restricted availability of randomized, placebo-controlled clinical trial data, inclusion of data from open-label studies, lack of real-world (i.e., non-trial-based) EAM rates and a lack of EAM-specific direct and indirect costs with which to compare the results presented herein.