Impact of a step-therapy protocol for pregabalin on healthcare utilization and expenditures in a commercial population

Abstract

Objective:

To compare changes in healthcare resource utilization and costs among members with painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN), or fibromyalgia (FM) in a commercial health plan implementing pregabalin step-therapy with members in unrestricted plans.

Methods:

Retrospective study of outcomes associated with implementation of a pregabalin step-therapy protocol using claims data from Humana (‘restricted’ cohort) and Thomson Reuters MarketScan (‘unrestricted’ cohort). Members aged 18–65 years receiving treatment for pDPN, PHN, or FM during 2008 or 2009 were identified; cohorts were matched on diagnosis and geographic region. Baseline to follow-up changes in healthcare resource utilization and costs were determined using difference-in-differences (DID) analysis. Statistical models adjusting for covariates explored relationships between restricted access and outcomes.

Results:

A total of 3876 restricted cohort members were identified and matched to 3876 unrestricted cohort members. FM was the predominant diagnosis (84.7%). The unrestricted cohort was older (mean?=?49.0 (SD?=?10.4) years vs 47.6 (SD?=?10.5) years; p?<?0.001), and had greater comorbidity (RxRisk-V score?=?5.4 (SD?=?3.2) vs 4.4 (SD?=?2.9), p?<?0.001) than the restricted cohort. Compared with the unrestricted cohort, the restricted cohort demonstrated a greater year-over-year decrease in pregabalin utilization (?2.6%, p?=?0.008), and greater increases in physical therapy and disease-related outpatient utilization (3.7%, p?=?0.010 and 3.6%, p?=?0.022, respectively). There were no statistically significant net differences in all-cause or disease-related total healthcare, medical, or pharmacy costs between cohorts. After adjusting for baseline compositional differences between cohorts, restricted plan membership was associated with a net increase in all-cause medical ($1222; p?=?0.016) and disease-related healthcare costs ($859; p?=?0.002). Limitations include use of a combined analysis for pDPN, PHN, and FM, especially since the observed results were likely driven by FM; an inability to link the prescribing of a medication with the condition of interest, which is common to claims analyses; and lack of pain severity information.

Conclusions:

Implementation of a pregabalin step-therapy protocol resulted in lower pregabalin utilization, but this restriction was not associated with reductions in total healthcare costs, medical costs, or pharmacy costs.     

Clinical characteristics,pharmacotherapy, and healthcare resource use among patients with fibromyalgia newly prescribed pregabalin or tricyclic antidepressants

Abstract

Objective:

To examine treatment patterns and costs among patients with fibromyalgia prescribed pregabalin or tricyclic antidepressants (TCAs).

Methods:

Using the LifeLink? Health Plan Claims Database, patients with fibromyalgia (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) newly prescribed (index date) TCAs (n?=?898) were identified and propensity score-matched (PSM) with patients newly prescribed pregabalin (n?=?898). Pain-related pharmacotherapy, comorbidities, and healthcare resource use/costs were examined during the 12 months, pre-index, and follow-up periods.

Results:

Both patient groups reported multiple comorbidities and received pain medications in the pre-index and follow-up periods. Among patients prescribed pregabalin, use of non-selective non-steroidal anti-inflammatory drugs (43.3% vs 39.8%), other anticonvulsants (28.6% vs 23.3%), and tetracyclic/miscellaneous antidepressants (28.5% vs 25.8%) significantly decreased, and cyclooxygenase 2 (COX-2) inhibitors (7.7% vs 10.4%), TCAs (4.8% vs 7.9%), and topical agents (10.8% vs 15.1%) increased in the follow-up period (p?<?0.05). Among patients prescribed TCAs, there were significant decreases in muscle relaxants (42.0% vs 38.4%) and sedative hypnotics (27.4% vs 23.9%), and increases in COX-2 inhibitors (5.8% vs 7.9%) and anticonvulsants (25.1% vs 33.7%; p?<?0.05). There were increases (p?<?0.0001) in pharmacy costs in both cohorts and total healthcare costs in the pregabalin cohort from pre-index to follow-up. Median total costs were higher (p?<?0.05) in the pregabalin group vs TCAs in the pre-index ($9935 vs $8771) and follow-up ($10,689 vs $8379) periods.

Limitations:

Despite attempts to address bias through PSM, the higher pre-index costs in the pregabalin cohort suggest a channeling of patients with more severe fibromyalgia to pregabalin.

Conclusions:

Patients with fibromyalgia prescribed pregabalin or TCAs had multiple comorbidities and a sizeable pain medication burden, which increased in the follow-up period for both cohorts. Only 5% of pregabalin initiators had been treated with concomitant TCAs at baseline, suggesting that TCAs were inappropriate for these patients owing to their contraindications.     

Clinical comorbidities,treatment patterns,and healthcare costs among patients with fibromyalgia newly prescribed pregabalin or duloxetine in usual care

Abstract

Objective:

To assess comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with fibromyalgia (FM) newly prescribed pregabalin or duloxetine (index event) in usual care settings.

Methods:

Using the LifeLink? Health Plan Claims Database, patients with FM (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) were identified. Patients initiated on duloxetine were propensity score-matched with patients initiated on pregabalin (n?=?826; mean age [standard deviation] of 48.3 [9.3] years for both groups). Prevalence of comorbidities, pain-related pharmacotherapy, and healthcare resource use/costs were examined during the 12-month pre-index and follow-up periods.

Results:

Both patient groups had multiple comorbidities and a substantial pain-related and adjuvant medication burden. In the pregabalin group, use of other anticonvulsants decreased significantly (31.6% vs 24.9%), whereas use of serotonin-norepinephrine reuptake inhibitors (SNRIs; 16.5% vs 22.5%) and topical agents (10.1% vs 13.2%) increased in the follow-up period (p?<?0.01). In the duloxetine group, there were significant decreases in the use of other SNRIs (13.0% vs 5.7%), selective serotonin reuptake inhibitors (41.3% vs 21.7%), and tricyclic antidepressants (18.8% vs 13.2%), and an increase in the use of anticonvulsants (28.6% vs 40.1%; p?<?0.0001). There were significant increases (p?<?0.0001) in pharmacy and total healthcare costs in both cohorts, and a significant increase in outpatient costs (p?=?0.0084) in the duloxetine cohort from pre-index to follow-up. There were no significant differences in median total healthcare costs between the pregabalin and duloxetine groups in both the pre-index ($10,159 vs $9,556) and follow-up ($11,390 vs $11,746) periods.

Limitations:

Limitations of this study are typical of those associated with retrospective database analyses.

Conclusions:

Patients with FM prescribed pregabalin or duloxetine were characterized by a significant comorbidity and pain/adjuvant medication burden. Although healthcare costs increased in both groups, there were no statistically significant differences in direct healthcare costs between the two groups.     

The cost-effectiveness of pregabalin in the treatment of fibromyalgia: US perspective

Abstract

Objective:

To evaluate the cost-effectiveness of pregabalin in the treatment of fibromyalgia in a US patient population.

Methods:

A decision-analytic model was developed comparing pregabalin 150?mg twice a day (BID) and pregabalin 225?mg BID to placebo, duloxetine, gabapentin, tramadol, milnacipran, and amitriptyline in patients with severe fibromyalgia (Fibromyalgia Impact Questionnaire score >59; pain score >6.5). The model estimated response rates for all treatments at 12 weeks based on three randomized trials with pregabalin and a systematic review of published randomized controlled trials. Response was categorized as ≥30% improvement in baseline pain score plus global impression of change rating of much improved or very much improved. After 12 weeks of treatment, responders to treatment entered a treatment Markov model in which response was maintained, lost, or treatment discontinued. The cost-effectiveness end-points were cost per responder at 12 weeks and 1 year. Resource use was estimated from published studies and costs were estimated from the societal perspective.

Results:

Over 12 weeks, total cost per patient was $229 higher with pregabalin 150?mg BID than placebo, whereas pregabalin 225?mg BID was $866 less costly than placebo. At 1 year, pregabalin was cost saving and more effective than placebo, duloxetine, tramadol, milnacipran, and gabapentin. Compared with amitriptyline, pregabalin was not cost-effective at both dosages, although when excluding old and methodologically weak studies of clinical effectiveness of amitriptyline, pregabalin 225?mg BID became cost saving and pregabalin 150?mg BID was cost-effective.

Limitations:

Comparisons between pregabalin and other active agents are based on indirect comparisons, not head-to-head trials, and so should be interpreted with caution. Limitations for comparators include an inability to access sub-group data, inconsistency of response definitions, inclusion of older trials, and absence of long-term studies.

Conclusions:

This model found pregabalin to be cost-effective in treating patients with severe fibromyalgia.     

Comparison of second-generation antipsychotic treatment on psychiatric hospitalization in Medicaid beneficiaries with bipolar disorder

Abstract

Objective:

To compare second-generation antipsychotics on time to and cost of psychiatric hospitalization in Medicaid beneficiaries with bipolar disorder.

Methods:

Retrospective study using healthcare claims from 10 US state Medicaid programs. Included beneficiaries were aged 18–64, initiated a single second-generation antipsychotic (aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone) between 1/1/2003–6/30/2008 (initiation date?=?index), and had a medical claim with an ICD-9-CM diagnosis code for bipolar disorder. A 360-day post-index period was used to measure time to and costs of psychiatric hospitalization (inpatient claims with a diagnosis code for a mental disorder [ICD-9-CM 290.xx–319.xx] in any position). Cox proportional hazards models and Generalized Linear Models compared time to and costs of psychiatric hospitalization, respectively, in beneficiaries initiating aripiprazole vs each other second-generation antipsychotic, adjusting for beneficiaries’ baseline characteristics.

Results:

Included beneficiary characteristics: mean age 36 years, 77% female, 80% Caucasian, aripiprazole (n?=?2553), mean time to psychiatric hospitalization or censoring?=?85 days; olanzapine (n?=?4702), 81 days; quetiapine (n?=?9327), 97 days; risperidone (n?=?4377), 85 days; ziprasidone (n?=?1520), 82 days. After adjusting for baseline characteristics, time to psychiatric hospitalization in beneficiaries initiating aripiprazole was longer compared to olanzapine (hazard ratio [HR]?=?1.52, p?<?0.001), quetiapine (HR?=?1.40, p?<?0.001), ziprasidone (HR?=?1.33, p?=?0.032), and risperidone, although the latter difference did not reach significance (HR?=?1.18, p?=?0.13). The adjusted costs of psychiatric hospitalization in beneficiaries initiating aripiprazole were significantly lower compared to those initiating quetiapine (incremental per-patient per-month difference?=?$42, 95% CI?=?$16–66, p?<?0.05), but not significantly lower for the other comparisons.

Limitations:

This study was based on a non-probability convenience sample of the Medicaid population. Analyses of administrative claims data are subject to coding and classification error.

Conclusions:

Medicaid beneficiaries with bipolar disorder initiating aripiprazole had significantly longer time to psychiatric hospitalization than those initiating olanzapine, quetiapine, or ziprasidone, and significantly lower adjusted costs for psychiatric hospitalization than those initiating quetiapine.     

Healthcare resource utilization and costs associated with venous thromboembolism in cancer patients treated with anticoagulants

Abstract

Objective: The standard of care for cancer-related venous thromboembolism (VTE) has been low molecular weight heparin (LMWH), but oral anticoagulants are also widely prescribed. This study compared VTE-related healthcare resource utilization and costs of cancer patients treated with anticoagulants.

Methods: Claims data from Humana Database (January 1, 2013–May 31, 2015) were analyzed. Based on the first anticoagulant received, patients were classified into LMWH, warfarin, or rivaroxaban cohorts. Characteristics were evaluated during the 6 months pre-index date (i.e. the first VTE); VTE-related resource utilization and costs were evaluated during follow-up. Cohorts were compared using rate ratios, and p-values and 95% confidence intervals were calculated. Healthcare costs were evaluated per-patient-per-year (PPPY) and compared using mean cost differences.

Results: A total of 2,428 patients (LMWH: n?=?660; warfarin: n?=?1,061; rivaroxaban: n?=?707) were included. Compared to patients treated with LMWH, patients treated with rivaroxaban had significantly fewer VTE-related hospitalizations, hospitalization days, and emergency room and outpatient visits, resulting in an increase of $12,000 VTE-related healthcare costs PPPY with LMWH vs rivaroxaban. Patients treated with rivaroxaban had significantly lower VTE-related resource utilization compared to patients treated with warfarin; however, VTE-related costs were similar between cohorts. The higher drug costs ($1,519) were offset by significantly lower outpatient (?$1,039) and hospitalization costs (?$522) in rivaroxaban relative to the warfarin cohort.

Conclusions: Healthcare resource use and costs associated with VTE treatment in cancer patients are highest with LMWH relative to warfarin and rivaroxaban.     

Economic evaluation of duloxetine as a first-line treatment for painful diabetic peripheral neuropathy in Mexico

Abstract

Objective:

To perform an economic evaluation of duloxetine, pregabalin, and both branded and generic gabapentin for managing pain in patients with painful diabetic peripheral neuropathy (PDPN) in Mexico.

Research design and methods:

The analysis was conducted using a 3-month decision model, which compares duloxetine 60?mg once daily (DUL), pregabalin 150?mg twice daily (PGB), and gabapentin 600?mg three-times daily (GBP) for PDPN patients with moderate-to-severe pain. A systematic review was performed and placebo-adjusted risk ratios for achieving good pain relief (GPR), adverse events (AE), and withdrawal owing to intolerable AE were calculated. Direct medical costs included drug acquisition and additional visits due to lack of efficacy (poor pain relief) or intolerable AE. Unit costs were taken from local sources. Adherence rates were used to estimate the expected drug costs. All costs are expressed in 2010 Mexican Pesos (MXN). Utility values drawn from published literature were applied to health states. The proportion of patients with GPR and quality-adjusted life years (QALY) were assessed.

Results:

Branded-GBP was dominated by all the other options. PGB was more costly and less effective than DUL. Compared with branded-GBP and PGB, DUL led to savings of 1.01 and 1.74 million MXN (per 1000 patients). The incremental cost per QALY gained with DUL used instead of generic-GBP was $102 433 MXN. This amount is slightly lower than the estimated gross domestic product per capita in Mexico for 2010. During a second-order Monte Carlo simulation, DUL had the highest probability of being cost-effective (61%), followed by generic-GBP (25%) and PGB (14%).

Limitations:

Study limitations include a short timeframe and using data from different dosage schemes for GBP and PGB.

Conclusions:

This study suggests that DUL provides overall savings and better health outcomes compared with branded-GBP and PGB. Administering DUL rather than generic-GBP is a cost-effective intervention to manage PDPN in Mexico.     

Cost-utility of pregabalin as add-on to usual care versus usual care alone in the management of peripheral neuropathic pain in Belgium

Abstract

Background and objectivess:

The cost effectiveness of pregabalin as an add-on to the standard treatment of Belgian patients with post-herpetic neuralgia (PHN) had been demonstrated in a previously published Markov model. The purpose of this study was to update that model with more recent cost data and clinical evidence, and reevaluate the cost effectiveness from the payer’s perspective of add-on pregabalin in a wider set of NeP conditions.

Methods:

The model, featuring 4-week cycles and a 1-year time horizon, consisted in four possible health states: mild, moderate or severe pain and withdrawn from therapy. Three versions of the model were developed, using transition probabilities derived from pain scores reported in three placebo-controlled studies. The two treatment arms were ‘usual care’ or ‘usual care?+?pregabalin’. Resource use and utility data were obtained from a chart review and unit costs from recent published data. The final outcome of the model was the incremental cost per quality-adjusted life-year (QALY) gained when adding pregabalin to standard care.

Results:

Based on 1000 simulations, two versions of the model showed that pregabalin was dominant respectively in 94.8% and 67.2% of the simulations, while the incremental cost per QALY was below €32,000/QALY in respectively 99.1% and 94.6% of the simulations. The third version did not show cost effectiveness, despite an incremental cost of only €300 after 1 year. However, in the corresponding study, patients seemed less responsive to GABA analogs, since 55% of them had failed to respond to gabapentin before study inclusion.

Limitations:

The studies upon which the model is based have a short follow-up time as compared to the model horizon. The endpoints of two studies were only provided at the aggregated level and do not necessarily reflect the real practice.

Conclusion:

Based on this analysis, it can be concluded that from a Belgium payer perspective pregabalin offers a slight increase in quality of life in the studied populations as compared to standard care. Pregabalin is cost effective in the majority of cases except in one published clinical study, despite a low incremental cost per year (€300).     

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.     

Healthcare utilization and costs in patients with tuberous sclerosiscomplex-related renal angiomyolipoma

Objective: To quantify healthcare utilization and costs in patients with tuberous sclerosis complex (TSC) and renal angiomyolipoma (AML) in a matched cohort of patients without TSC or AML.

Methods: Administrative data from the MarketScan Research Databases were used to select patients with TSC and renal AML during January 1, 2000–March 31, 2013 from the Commercial database and January 1, 2000–June 30, 2012 from the Medicaid database. Patients were required to have at least 30 days of follow-up from initiation into the study, and were followed until inpatient death, end of insurance coverage, or the end of study. Age, calendar year, and payer-matched controls that had no TSC and no AML were selected. All-cause annualized healthcare utilization and costs were calculated by service category.

Results: A total of 218 patients under 18 years and 377 patients 18 years and older with TSC-renal AML were selected from the Commercial database, and matched to 654 and 1,131 controls, respectively. Thirty-eight patients under 18 years and 110 patients 18 years or older with TSC-renal AML were selected from the Medicaid database, and matched to 54 and 212 controls, respectively. Within the Commercial cohort, and across both age groups, TSC-renal AML patients utilized more healthcare services than their matched controls. Within the Medicaid cohort, in both age groups, utilization was higher in TSC-renal AML patients vs control patients for inpatient admissions, emergency room visits, physician office visits, and hospital-based outpatient visits. Across age groups and in both the Commercial and Medicaid cohorts, the annual average total costs were significantly higher in TSC-renal AML patients compared to control patients (p?Conclusions: Compared to controls, TSC-renal AML patients incurred substantially higher annual healthcare utilization and costs.     

Indirect costs associated with metastatic breast cancer

Abstract

Objective:

To compare the indirect costs of productivity loss between metastatic breast cancer (MBC) and early stage breast cancer (EBC) patients, as well as their respective family members.

Methods:

The MarketScan® Health and Productivity Management database (2005–2009) was used. Adult BC patients eligible for employee benefits of sick leave and/or short-term disability were identified with ICD-9 codes. Difference in sick leave and short-term disability days was calculated between MBC patients and their propensity score matched EBC cohort and general population (controls) during a 12-month follow-up period. Generalized linear models were used to examine the impact of MBC on indirect costs to patients and their families.

Results:

A total of 139 MBC, 432 EBC, and 820 controls were eligible for sick leave and 432 MBC, 1552 EBC, and 4682 controls were eligible for short-term disability (not mutually exclusive). After matching, no statistical difference was found in sick leave days and the associated costs between MBC and EBC cohorts. However, MBC patients had significantly higher short-term disability costs than EBC patients and controls (MBC: $6166?±?$9194 vs EBC: $3690?±?$6673 vs Controls: $558?±?$2487, both p?<?0.001). MBC patients had more sick leave cost than controls ($2383?±?$5539 vs $1282?±?$2083, p?<?0.05). Controlling for covariates, MBC patients incurred 47% more short-term disability costs vs EBC patients (p?=?0.009). Older patients (p?=?0.002), non-HMO payers (p?<?0.05), or patients not receiving chemotherapy during follow-up (p?<?0.001) were associated with lower short-term disability costs. MBC patients’ families incurred 39.7% (p?=?0.06) higher indirect costs compared to EBC patients’ families after controlling for key covariates.

Conclusion:

Productivity loss and associated costs in MBC patients are substantially higher than EBC patients or the general population. These findings underscore the economic burden of MBC from a US societal perspective. Various treatment regimens should be evaluated to identify opportunities to reduce the disease burden from the societal perspective.