A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2- Metastatic Breast Cancer.

PIK3CA mutation frequency varies among breast cancer (BC) subtypes. Recent evidence suggests combination therapy with the PI3K inhibitor (PI3Ki) alpelisib and endocrine therapy (ET) improves response rates and progression-free survival (PFS) in PIK3CA-mutant, hormone receptor positive (HR+) BC versus ET alone; thus, better understanding the clinical and epidemiologic elements of these mutations is warranted. This systematic review characterizes the PIK3CA mutation epidemiology, type of testing approaches (e.g., liquid or tissue tumor biopsy), and stability/concordance (e.g., consistency in results by liquid versus solid tumor sample, by the same method over time) in patients with HR+/HER2- advanced (locally unresectable) or metastatic disease (HR+/HER2- mBC) and explores performance (e.g., pairwise concordance, sensitivity, specificity, or predictive value) of respective mutation findings. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts (i.e., AACR, ASCO, SABCS, ECCO, and ESMO conferences between 2014 and 2017) identified 39 studies of patients with HR+, HER2- mBC. The median prevalence of PIK3CA mutation was 36% (range: 13.3% to 61.5%); identified testing approaches more commonly used tissue over liquid biopsies and primarily utilized next-generation sequencing (NGS), polymerase chain reaction (PCR), or Sanger sequencing. There was concordance and stability between tissues (range: 70.4% to 94%) based on limited data. Given the clinical benefit of the PI3Ki alpelisib in patients with PIK3CA mutant HR+/HER2- mBC, determination of tumor PIK3CA mutation status is of importance in managing patients with HR+/HER2- mBC. Prevalence of this mutation and utility of test methodologies likely warrants PIK3CA mutation testing in all patients with this breast cancer subtype via definitive assessment of PIK3CA mutational status.

A Systematic Literature Review of the Prognostic and Predictive Value of PIK3CA Mutations in HR+/HER2- Metastatic Breast Cancer.

PIK3CA mutations may have prognostic value for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer, representing an important potential target for systemic therapy. Prognostic and predictive values associated with PIK3CA mutations are not well understood. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and conference abstracts was performed for English-language articles published January 1993 through April 2019. Articles were categorized by treatment arms based on experimental and treatment drug classes. Information on progression-free survival (PFS), hazard ratios, overall survival, response rate, and clinical benefit rate was obtained. A total of 17 studies were included. Among those evaluating non-PI3Ki based therapies, 91% showed numerically shorter median PFS, ranging from 1.5 to 19.2 months and 1.8 to 29.6 months for the mutant versus non-mutant subgroups, respectively. Where reported (n = 13 studies), PFS was shorter between those arms offering endocrine monotherapy (range, 1.6-14.7 months) compared with a corresponding targeted therapy + endocrine monotherapy (range, 3.9-29.6 months). Of 5 PI3Ki-based arms comparing PFS, higher median PFS in PIK3CA mutant versus non-mutant cases was demonstrated. PFS was shorter for patients with PIK3CA mutant (range, 1.6-19.2 months) compared with PIK3CA wild-type (range, 1.8-29.6 months) in 10 (71%) of 14 treatment arms reporting PFS. Studies (n = 4) not reporting PFS reported response rate, but there were no clear directional trends. The presence of PIK3CA mutations may be associated with worse clinical outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Clinical outcomes such as PFS may be improved using a combination of PI3Ki-based therapies and endocrine therapies among this population. However, more research is warranted to fully elucidate this association.

Content validity of the National Comprehensive Cancer Network - Functional Assessment of Cancer Therapy - Breast Cancer Symptom Index (NFBSI-16) and Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form with advanced breast cancer patients.

BACKGROUND: The purpose of this study is to evaluate the content validity of the National Comprehensive Cancer Network - Functional Assessment of Cancer Therapy - Breast Cancer Symptom Index (NFBSI-16) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10b among patients with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. METHODS: Cognitive debriefing interviews sought to evaluate patients' ability to read, understand, and meaningfully respond to the questionnaires, as well as to evaluate the questionnaires' relevance in the target patient population. Interviews were conducted by telephone and lasted approximately 90 min. Audio recordings were transcribed, anonymized, and analyzed using qualitative data analysis software. RESULTS: Fifteen cognitive debriefing interviews were conducted with women (mean age 66.0 years [standard deviation = 12.4]). Patients reported metastases in the bone (86.7%), liver (20.0%), lung (13.3%), skin (6.7%), and lymph node (6.7%) (not mutually exclusive). All patients for whom data were available demonstrated understanding of the instructions and the recall period of the NFBSI-16 (n = 14/14, 100.0%) and the PROMIS (n = 14/14, 100.0%). Greater than 90% of patients demonstrated understanding of each of the items in the NFBSI-16 and the PROMIS. Greater than 70% of patients demonstrated understanding of the response options of the NFBSI-16, > 90% understood response options of PROMIS Items 1-6, and ≥ 50% understood response options of PROMIS Items 7-10. Conceptual relevance was supported for most items in both questionnaires based on patients' reports of experiencing the concepts as part of their breast cancer experience. CONCLUSIONS: The results of the cognitive debriefing interviews provide evidence that the NFBSI-16 and PROMIS Physical Function Short Form 10b have content validity in the HR+/HER2- advanced breast cancer patient population. Patients may benefit from additional instructions at the point the response options reverse direction in the PROMIS.

Understanding key symptoms, side effects, and impacts of HR+/HER2- advanced breast cancer: qualitative study findings.

BACKGROUND: Patients with breast cancer experience a variety of disease symptoms and treatment-related side effects that can adversely affect functioning. The breast cancer experience may differ across disease stages and biomarker subtypes. This study identified relevant disease symptoms, treatment-related side effects, and physical functioning impacts in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. METHODS: One-on-one concept elicitation interviews were conducted with 15 patients with HR+/HER2- advanced breast cancer. Open-ended questions about patient experience with breast cancer and its treatment were drawn from a semi-structured interview guide. All interviews were audio-recorded and transcribed verbatim, and codes were used to document and organize patient descriptions of their experiences. Coded concepts were defined, supported by exemplary patient quotes, and analyzed for frequency of mention and saturation. Five interviews with experienced oncologists were conducted to supplement the concept elicitation interviews. RESULTS: The average age of the patients was 66 years. Most (53%) self-identified as White/Caucasian; 40%, as Black/African American. Patients were reported to have metastases to bone (87%), liver (20%), lung (13%), skin (7%), and lymph nodes (7%). The most frequently reported disease-related concepts were fatigue and lump in breast (47% each) and pain (40%), while the most frequently reported treatment-related side effects were hair loss (67%), fatigue/tiredness (47%), and nausea (40%). Patients identified 10 concepts associated with both breast cancer and its treatment, including fatigue/tiredness, shortness of breath, weakness, and nausea. The most frequently reported impacts on physical function included working around home (73%), walking (73%), and cooking (53%). The most frequently reported symptoms and side effects from the expert perspective included fatigue, pain, and hot flashes (n = 5 each, 100%), while the ability to work (n = 5, 100%) and walk (n = 3, 60%) were reported impacts, aligning with those concepts reported by patients. The resulting concepts were organized into a patient-based conceptual model. CONCLUSIONS: Patients have varied experiences due to HR+/HER2- advanced breast cancer and its treatment, and commonly experience fatigue/tiredness, hair loss, general pain, lump in breast, and nausea, as well as impacts to physical functioning (specifically, activities of daily living and mobility).

Predictors of systemic therapy sequences following a CDK 4/6 inhibitor-based regimen in post-menopausal women with hormone receptor positive, HEGFR-2 negative metastatic breast cancer.

Objective: To identify systemic treatment in the real-world following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDKi) among post-menopausal women with hormone receptor positive, human epidermal growth factor receptor 2 Negative (HR+/HER2-) metastatic breast cancer (mBC).Methods: Post-menopausal women with HR+/HER2- mBC were identified from MarketScan claims databases between January 1, 2012 and October 31, 2017. Eligible mBC patients who received a CDKi-based line of therapy following metastasis diagnosis were selected. A line of therapy ended at the earlier of systemic therapy discontinuation, switch to new treatment, or censoring.Results: In total, 525 patients that received systemic therapy after a CDKi-based line were included (39.6% transitioned from use of a CDKi-based regimen in first line following metastasis diagnosis to any second line, and 60.4% shifted from a CDKi-based [second, third, or fourth line] to a subsequent line). Of post-CDKi second line regimens (n = 208), 38.0% were endocrine only, 35.6% were chemotherapy-based, 14.4% were everolimus-based, 9.6% were also CDKi-based line, and 2.4% were others. After adjusting for demographic and clinical characteristics, patients transitioning from a CDKi-based line to chemotherapy (vs others) had a trend of being more likely to have recurrent rapidly progressing disease, and were significantly less likely to have the prior CDKi-based line in combination with an AI (both p < .05).Conclusions: This population-based study suggests that rapidly progressing disease, metastatic site location, age, and endocrine therapy partner may be predictive of subsequent systemic therapy regimen selection after progression on a CDKi-based line therapy in patients with HR+/HER2- mBC.

Burden of Infections Among Chronic Myeloid Leukemia Patients Receiving Dasatinib or Nilotinib: A Real-World Retrospective Healthcare Claims Study in the United States.

INTRODUCTION: Tyrosine kinase inhibitors (TKI) have been demonstrated to prolong survival in patients with chronic myeloid leukemia (CML). However, TKIs may be associated with an increased risk of infections. This study compared healthcare resource utilization (HRU) and costs among patients with CML receiving dasatinib or nilotinib, with a focus on infection-related economic outcomes. METHODS: Two large administrative databases were used to identify adult patients newly diagnosed with CML who initiated dasatinib or nilotinib as first- (1L) or second-line (2L) therapy and were classified into the following 1L (dasatinib 1L/nilotinib 1L cohorts) or 2L (dasatinib 2L/nilotinib 2L) cohorts based on the initiated 1L/2L TKI therapy. Infection-related HRU and healthcare costs were compared between cohorts, separately for 1L and 2L. RESULTS: Cohorts included 1156 patients in the dasatinib 1L and 677 patients in the nilotinib 1L cohorts, 322 patients in the dasatinib 2L, and 207 in the nilotinib 2L cohorts. In 1L and 2L, infection-related HRU was higher for dasatinib than nilotinib cohorts. Infection-related inpatient (IP) days constituted a larger proportion of all-cause IP days in the 1L/2L dasatinib than 1L/2L nilotinib cohorts (dasatinib 1L/2L: 53%/58%; nilotinib 1L/2L: 50%/46%). Compared to the nilotinib cohort, the dasatinib cohort had higher all-cause total costs per patient per year by US$17,901 in 1L and $28,625 in 2L. Of the total cost difference, infection-related were $6048 (34%) in 1L and $28,192 (99%) in 2L, largely driven by IP cost differences (1L/2L: 96%/98%). CONCLUSIONS: Dasatinib was associated with higher HRU and healthcare costs compared to nilotinib, particularly related to infections. FUNDING: Novartis Pharmaceutical Corporation.

Systematic Literature Review of the Impact of Endocrine Monotherapy and in Combination with Targeted Therapy on Quality of Life of Postmenopausal Women with HR+/HER2- Advanced Breast Cancer.

INTRODUCTION: A major treatment goal for advanced breast cancer (ABC) is to maintain or ideally improve patient quality of life (QoL). Given the changing disease landscape, this systematic literature review (SLR) aims to assess the impact of endocrine therapies (ET), including ET monotherapy (ET mono) and ET combined with targeted therapy (ET + TT), on QoL of women with HR+/HER2- ABC. METHODS: A SLR was conducted to identify randomized controlled trials (RCTs) meeting the following criteria: (1) included ET mono or ET + TT, (2) reported QoL outcomes, (3) focused on women with HR+/HER2- ABC, and (4) published after 2007 (when standardized HER2 testing became available). The databases searched included MEDLINE, EMBASE, Cochrane Library, and key conference proceedings from 2013 to 2016. QoL outcomes for ET mono, ET + TT, and comparisons between the two were summarized from the identified trials. RESULTS: A total of 11 studies (representing 6 RCTs) were identified. The study populations included first-line (5 studies) and ET-failure settings (6 studies). Across settings, global health status (GHS) maintained or deteriorated slightly on these treatments during the trial period. Time to deterioration (TTD) in QoL measured by GHS was analyzed in 6 studies and 4 RCTs. In the first-line setting, reported median TTD in GHS was similar between ET mono and ET + TT (7.2-13.8 months in ET mono; 11.1 months in ET + TT). In the ET-failure setting, ET + TT showed significantly longer TTD vs. ET mono in GHS (median 5.6-8.4 months in ET mono and 8.3-11.7 months in ET + TT) and some additional domains. CONCLUSIONS: ET + TT users experienced similar QoL in the first-line and ET-failure setting relative to patients on ET mono. Moreover, ET + TT users experienced better QoL outcomes in some domains in the ET-failure setting relative to ET mono users. FUNDING: Novartis.

First-line treatment disruption among post-menopausal women with HR+/HER2- metastatic breast cancer: a retrospective US claims study.

OBJECTIVE: This study assessed disruption of first-line treatments initiated after the approval of the first CDK 4/6 inhibitor, palbociclib, among post-menopausal women with HR+/HER2- metastatic breast cancer (mBC) in the US. METHODS: Post-menopausal women with HR+/HER2- mBC who initiated first-line endocrine therapy or chemotherapy (index therapy) between February 3, 2015 (palbociclib approval date) and February 29, 2016 (end of data) were identified from the Symphony Source Lx database. Patients were required to have continuous quarterly activity (defined as ≥1 pharmacy or medical claim) for 12 months prior to and 1 month after the initiation of the index therapy (index date). Treatment disruption was defined as a treatment gap of ≥60 days or adding an agent after the original therapy. Kaplan-Meier analyses were conducted to estimate treatment disruption rates during the 6 months following the index date. Patients without treatment disruption were censored at the end of continuous quarterly activity or end of data. RESULTS: A total of 8,160 and 2,153 eligible patients initiated endocrine therapy or chemotherapy as their first-line mBC treatment, with a median follow-up of 6.7 and 7.6 months, respectively. The three most prevalent metastatic sites were bone (28.1-42.2%), liver (8.8-17.3%), and lung (8.6-9.5%). Overall, 37.7% (n = 3,074) of patients receiving endocrine therapy and 86.1% (n = 1,852) of patients receiving chemotherapy encountered treatment disruption at 6 months (log-rank test p < .05). CONCLUSIONS: Treatment disruption rates of first-line therapies were sub-optimal among post-menopausal women with HR+/HER2- mBC, primarily driven by chemotherapy users. New therapies or interventions are needed to reduce treatment disruption in this patient population.

Real-world palbociclib dosing patterns and implications for drug costs in the treatment of HR+/HER2- metastatic breast cancer.

BACKGROUND: This study described real-world palbociclib dosing patterns and associated impacts on treatment costs for HR+/HER2- metastatic breast cancer (mBC) in the US. METHODS: Postmenopausal women with HR+/HER2- mBC who initiated palbociclib-based therapy (initiation date = index date) between 02/03/2015 (palbociclib approval) and 02/29/2016, and continuous quarterly activity 1 year before and 6 months after the index date, were identified in the Symphony Health Solutions database. Rates of 1) dose reduction (≥25 mg dose decrease/daily), and 2) reduction or interruption (>60 day gap in continuous drug supply) were assessed using Kaplan-Meier analyses. Drug wastage cost was estimated based on overlapping days between two prescription fills: the last original dose fill and the first reduced dose fill. RESULTS: 1,242 patients initiated palbociclib-based therapy (mean age = 62.7 years, median follow-up = 8.7 months). During the 12-month post-index period, across the first four lines, dose reduction rates were 31.9-33.7% and dose reduction/interruption rates were 63.5-80.9%. A total of 411 (33.1%) patients changed dose, among whom 128 (31.1%) experienced prescription fill overlap (average = 11.1 days). Mean potential drug wastage cost among patients with fill overlap was $5,471. CONCLUSIONS: Most patients receiving palbociclib experienced dose reduction or interruption early in treatment; the associated drug wastage may lead to considerable costs.

Systematic review and network meta-analysis of the efficacy and safety of tumour necrosis factor inhibitor-methotrexate combination therapy versus triple therapy in rheumatoid arthritis.

OBJECTIVE: Clinical trials have not consistently demonstrated differences between tumour necrosis factor inhibitor (TNFi) plus methotrexate and triple therapy (methotrexate plus hydroxychloroquine plus sulfasalazine) in rheumatoid arthritis (RA). The study objective was to estimate the efficacy, radiographic benefits, safety and patient-reported outcomes of TNFi-methotrexate versus triple therapy in patients with RA. METHODS: A systematic review and network meta-analysis (NMA) of randomised controlled trials of TNFi-methotrexate or triple therapy as one of the treatment arms in patients with an inadequate response to or who were naive to methotrexate was conducted. American College of Rheumatology 70% response criteria (ACR70) at 6 months was the prespecified primary endpoint to evaluate depth of response. Data from direct and indirect comparisons between TNFi-methotrexate and triple therapy were pooled and quantitatively analysed using fixed-effects and random-effects Bayesian models. RESULTS: We analysed 33 studies in patients with inadequate response to methotrexate and 19 in patients naive to methotrexate. In inadequate responders, triple therapy was associated with lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate (OR 0.35, 95% credible interval (CrI) 0.19 to 0.64). Most secondary endpoints tended to favour TNFi-methotrexate in terms of OR direction; however, no clear increased likelihood of achieving these endpoints was observed for either therapy. The odds of infection were lower with triple therapy than with TNFi-methotrexate (OR 0.08, 95% CrI 0.00 to 0.57). There were no differences observed between the two regimens in patients naive to methotrexate. CONCLUSIONS: In this NMA, triple therapy was associated with 65% lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate in patients with inadequate response to methotrexate. Although secondary endpoints numerically favoured TNFi-methotrexate, no clear differences were observed. The odds of infection were greater with TNFi-methotrexate. No differences were observed for patients naive to methotrexate. These results may help inform care of patients who fail methotrexate first-line therapy.

Comparing Biologic Cost Per Treated Patient Across Indications Among Adult US Managed Care Patients: A Retrospective Cohort Study.

BACKGROUND: The relative cost of biologics in the treatment of autoimmune disorders, including rheumatoid arthritis, psoriatic arthritis, psoriasis, and ankylosing spondylitis, is a key consideration for managed care payers. OBJECTIVES: Our objective was to estimate biologic costs and treatment patterns in US managed care patients with rheumatoid arthritis, psoriatic arthritis, psoriasis, and/or ankylosing spondylitis. METHODS: This retrospective study used administrative claims data from the HealthCore Integrated Research Database (HIRDSM) for adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, and/or ankylosing spondylitis who received abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab, or ustekinumab between 1 July 2009 and 31 January 2013. Biologic costs (based on drug utilization) and treatment patterns (discontinued, restarted after a >45-day gap, switched to another biologic, or persisted without switching or stopping) were analyzed for the first year post-index. RESULTS: Most of the 24,460 patients received etanercept (48 %), adalimumab (29 %), or infliximab (12 %) as the index biologic. On the index date, 44 % were new to biologic therapy and 56 % were continuing biologic therapy. Biologic cost per treated patient for 1 year was as follows: etanercept $US24,859, adalimumab $US26,537, and infliximab $US26,468. Treatment patterns across indications for etanercept, adalimumab, and infliximab were as follows: persistent (52, 49, 67 %), restarted (23, 21, 12 %), switched (12, 13, 11 %), and discontinued (14, 18, 10 %). CONCLUSIONS: These findings from a large health benefits organization in the USA are similar to those of several previous cost analyses assessing different populations, which demonstrates the external validity of the results from the previous studies, both over time and across large populations.

Treatment patterns and annual biologic costs in US veterans with rheumatic conditions or psoriasis.

OBJECTIVE: To determine annual biologic drug and administration costs to the US Veterans Health Administration (VHA) per treated patient with rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who received abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab, or ustekinumab. METHODS: Adults with at least one biologic claim between January 1, 2008 and December 31, 2011 were included. Evidence of enrollment in the VHA was required from 365 days before (pre-index) to 360 days after (post-index) the date of the first biologic claim (index date). Included patients had pre-index diagnoses of RA, PsO, PsA, and/or AS. Drug costs were from Federal Supply Schedule or 'Big Four' in November 2014. Administration costs were VHA fixed costs for infused ($169) and subcutaneous ($25) biologics. RESULTS: Of the 20,465 patients in the analysis, 10,711 received etanercept, 7838 received adalimumab, and 1196 received infliximab as the index biologic. In these patients, across all uses studied, the VHA incurred greater annual cost per treated patient for infliximab ($18,066) compared with adalimumab ($16,523) and etanercept ($16,526). In the first year post-index, ∼80% of patients were either persistent on these index biologics or re-started these index biologics after a ≥45-day treatment gap. Other biologics comprised <5% of the study population, with sample sizes ranging from 3-374 patients each. Cost by indication for biologics used by >20 patients ranged from $15,056 (etanercept) to $17,050 (abatacept) for RA; $16,697 (adalimumab) to $33,163 (ustekinumab) for PsO; $15,035 (etanercept) to $20,465 (infliximab) for PsA; and $14,239 (etanercept) to $18,536 (infliximab) for AS. LIMITATIONS: The model was limited to the VHA. Results for biologics other than adalimumab, etanercept, and infliximab were difficult to interpret because of small sample sizes. CONCLUSIONS: Infliximab has higher cost to the VHA than adalimumab or etanercept.

Biologic Cost per Effectively Treated Rheumatoid Arthritis Patient in a Large Managed Care Population: A Retrospective Cohort Study.

Background: Until recently, the lack of clinical outcomes information for rheumatoid arthritis (RA) in administrative claims databases limited their use in comparative effectiveness research. A validated claims-based algorithm has been developed to estimate the effectiveness of biologics for RA, allowing for estimation of cost and effectiveness in the same database. Objectives: To implement a validated claims-based effectiveness algorithm in a US managed care claims database to compute the 1-year biologic cost per effectively treated patient among first-line biologics approved for moderate-to-severe RA (abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab). Methods: This retrospective cohort study used administrative claims data for individuals in the HealthCore Integrated Research Database (HIRDSM). The first claim for a first-line biologic between July 1, 2009, and January 31, 2013, after 6 months of continuous enrollment, was defined as the index event and date. Patients were aged 18-63 years on the index date and had at least one claim for RA in the 6-month pre- index period. Biologic costs included plan and patient paid amounts on claims for the biologic drug and administration. The algorithm defined effectiveness during the 12-month post-index period as achieving all six of the following: high adherence (medication possession ratio ≥80% or infusions consistent with the product label); no increase in biologic dose or decrease in dosing interval; no new biologic; no new nonbiologic disease-modifying antirheumatic drug; no new or increased oral glucocorticoid use; and ≤1 glucocorticoid injection. Cost per effectively treated patient was calculated as the total biologic cost (drug and administration) divided by the number of patients categorized by the algorithm as effectively treated. Results: The cohort comprised 4844 patients (mean age 48.6 years, 76.4% female). Average first-year biologic cost ranged from $14 795 (golimumab) to $19 520 (abatacept). Average first-year biologic cost per effectively treated patient was significantly lower for etanercept ($50 217) than for golimumab ($56 427, p<0.001) adalimumab ($56 879, p<0.001), abatacept ($68 062, p<0.001), certolizumab pegol ($76 427, p<0.001), and infliximab ($95 126, p<0.001). Conclusions: In this application of a validated claims-based algorithm to a large managed care population, etanercept had the lowest 1-year biologic cost per effectively treated patient among first-line biologics.

Etanercept-Methotrexate Combination Therapy Initiators Have Greater Adherence and Persistence Than Triple Therapy Initiators With Rheumatoid Arthritis.

OBJECTIVE: To estimate adherence and persistence with etanercept plus methotrexate (ETN-MTX) combination therapy and MTX, hydroxychloroquine, and sulfasalazine triple therapy at 1 year following treatment initiation in adults with rheumatoid arthritis (RA). METHODS: This retrospective analysis used data from the Truven Health MarketScan Commercial and Medicare Supplemental databases from January 2009 to July 2013. Adherence was defined as having percentage of days covered >80% for all drugs within each regimen. Persistence was defined as no treatment gap >45 days for any drug and no addition or switching to other disease-modifying antirheumatic drugs. Multiple logistic regression models were employed in the analyses to control for potential confounders. RESULTS: A total of 3,724 ETN-MTX patients and 818 triple therapy patients were eligible. At 1 year, 27.9% who were taking ETN-MTX and 18.2% using triple therapy were adherent to all agents in their regimen (P < 0.0001), and 29.4% who were taking ETN-MTX and 23.2% using triple therapy were persistent (P < 0.001). After adjusting for confounders, ETN-MTX patients had significantly greater odds of being adherent (odds ratio [OR] 1.79, 95% confidence interval [95% CI] 1.47-2.17) and persistent (OR 1.45, 95% CI 1.20-1.72) compared with patients using triple therapy. CONCLUSION: Patients with RA initiating treatment with ETN-MTX combination therapy demonstrated greater adherence and persistence at 1 year than patients initiating triple therapy.

Prevalence and Incidence of Epilepsy in an Elderly and Low-Income Population in the United States.

BACKGROUND AND PURPOSE: The purpose of this study was to estimate the incidence and prevalence of epilepsy among an elderly and poor population in the United States. METHODS: Arizona Medicaid claims data from January 1, 2008 to December 31, 2010 were used for this analysis. Subjects who were aged ≥65 years and were continuously enrolled in any Arizona Medicaid health plans (eligible to patients with low income) for ≥12 months between January 1, 2008 and December 31, 2009 were considered eligible for inclusion in the study cohort. In addition to meeting the aforementioned criteria, incident and prevalent cases must have had epilepsy-related healthcare claims. Furthermore, incident cases were required to have a 1-year "clean" period immediately preceding the index date. Negative binomial and logistic regression models were used to assess the factors associated with epilepsy incidence and prevalence. RESULTS: The estimated epilepsy incidence and prevalence for this population in 2009 were 7.9 and 19.3 per 1,000 person-years, respectively. The incidence and prevalence rates were significantly higher for patients with comorbid conditions that were potential risk factors for epilepsy and were of younger age than for their non-comorbid and older counterparts (p<0.05). The prevalence rates were significantly higher for non-Hispanic Blacks and male beneficiaries than for non-Hispanic Whites and female beneficiaries, respectively (p<0.05). CONCLUSIONS: This patient population had higher epilepsy incidence and prevalence compared with the general US population. These differences may be at least in part attributable to their low socioeconomic status.

Impact of urinary incontinence on health-related quality of life, daily activities, and healthcare resource utilization in patients with neurogenic detrusor overactivity.

BACKGROUND: Neurogenic detrusor overactivity (NDO) leads to impaired health-related quality of life (HRQoL), productivity, and greater healthcare resource burden. The humanistic and economic burden may be more apparent in NDO patients with urinary incontinence (UI). The objective of this study was to compare the HRQoL, productivity, and health resource use (HRU) between continent and incontinent NDO patients. METHODS: A retrospective database analysis was conducted using the Adelphi Overactive Bladder (OAB)/UI Disease Specific Programme, a multi-national, cross-sectional survey reported from both patients' and physicians' perspectives. The population for this analysis included NDO patients with or without UI. General and disease-specific HRQoL were assessed using the EuroQoL-5D (EQ-5D), Incontinence Quality of Life questionnaire (I-QOL), and the Overactive Bladder Questionnaire (OAB-q). Productivity and daily activity impairment were measured using the Work Productivity and Activity Impairment (WPAI) questionnaire. HRU indicators included OAB-related surgery, OAB-related hospitalizations, incontinence pad usage, switching anticholinergics used for OAB due to inadequate response or adverse effects, and OAB-related physician visits. Bivariate analyses, multivariate ordinary least squares (OLS) regression analyses and published minimal clinically important differences (MCID) were used to assess relationships between incontinent status and the aforementioned outcome measures. RESULTS: A total of 324 NDO patients with or without urinary incontinence were included, averaging 54 years of age (SD 16), of whom 43.8 percent were male. Bivariate analyses detected no significant relationship between incontinent status and HRU variables. Regression analyses revealed that incontinent patients had clinically and statistically lower disease-specific HRQoL and greater impairment in daily activities as compared to continent patients. On average, incontinent patients scored 10 points lower on the I-QOL total score, 9 points lower on the OAB-q HRQoL score, 15 points higher on OAB-q symptom severity, and experienced 8.2 percent higher activity impairment due to their bladder condition (all p < 0.001). CONCLUSIONS: Incontinent NDO patients experience significantly lower HRQoL and activity impairment as compared to continent NDO patients.

Impact of urinary incontinence on healthcare resource utilization, health-related quality of life and productivity in patients with overactive bladder.

OBJECTIVE: To evaluate the impact of urinary incontinence (UI) on healthcare resource utilization (HRU), health-related quality of life (HRQoL) and productivity measures in patients with overactive bladder (OAB). PATIENTS AND METHODS: This retrospective, cross-sectional study used data from the Adelphi OAB/UI Disease Specific Programme, a multinational survey of patient- and physician-reported data, fielded between November 2010 and February 2011. The primary patient groups of interest were those with OAB, both with and without UI. Health-related quality of life and productivity measures were derived from the EuroQoL-5D, the Incontinence Quality of Life questionnaire, the Overactive Bladder Questionnaire, and the Work Productivity and Activity Impairment Questionnaire. Measures of HRU included OAB-related surgeries, OAB-related hospitalizations, incontinence pads, anticholinergic use and physician visits. Multivariate linear regression models and literature-based minimal clinically important differences were used to assess statistically significant and clinically meaningful differences in HRQoL and productivity measures between patients with OAB with UI and those without UI. RESULTS: A total of 1 730 patients were identified, with a mean age of 60.7 years, and 77.0% of them were women, 84.2% were non-Hispanic whites, and 71% were incontinent. Bivariate analyses showed that HRU was significantly higher among patients with OAB with UI than among those without UI in all categories except for the number of OAB-related physician visits. In both bivariate and multivariate analyses, incontinent patients presented with clinically and statistically significantly lower HRQoL and productivity measures with respect to all study endpoints, except for percentage of work time missed due to their OAB/UI. CONCLUSIONS: Urinary incontinence was associated with significantly higher HRU and lower HRQoL and productivity in this population of patients with OAB from five different countries. In addition to clinical considerations, the economic and humanistic impact of UI should be taken into account when evaluating treatment options for patients with OAB.

Economic burden and disparities in healthcare resource use among adult patients with cardiac arrhythmia.

BACKGROUND: As of 2012, approximately 4.3 million Americans experience some form of cardiac arrhythmia (CA). Assessment of economic burden and healthcare resource use on the overall CA population is limited. OBJECTIVES: To assess healthcare expenditure and disparities in healthcare resource use in patients with all forms of CA in the US. METHODS: Data from the Medical Expenditure Panel Survey were analyzed between 2004 and 2009. Patients aged≥18 years with any form of CA (identified via International Classification of Disorders Ninth Revision, Clinical Modification [ICD-9-CM] codes) were included. Primary independent variables included age, gender, race/ethnicity, and pharmacotherapy use. Outcomes of interest included total annual healthcare and prescription expenditures (inflation adjusted to 2011), use of anti-arrhythmic agents associated with CA, and inpatient, outpatient, or emergency room visits. Generalized linear models were used to assess the disparities across patient subgroups related to the outcomes. RESULTS: Annually, 5,750,440 individuals experienced CA in the US. Total direct annual healthcare cost of CA summed up to $US67.4 billion. Non-Hispanic whites and older adult patients had higher expenditures and use of healthcare resources (p<0.05). Female patients had significantly higher prescribed medication expenditures and a lower proportion of inpatient and emergency room visits related to arrhythmia (p<0.05). Patients taking anti-arrhythmic agents had significantly higher expenditure and a lower proportion of emergency department visits related to arrhythmia (p<0.05). CONCLUSIONS: CA represents a substantial economic burden in the US, especially for the older adult population. Patients other than non-Hispanic whites may not have adequate access to healthcare treatment for arrhythmia.

Association of patient demographics on quality of life in a sample of adult patients with cardiac arrhythmias.

PURPOSE: Identify predictors of quality of life (QOL) in patients with any form of cardiac arrhythmia (CA). METHODS: Data from the Medical Panel Expenditure Survey were analyzed from 2004 to 2009. Patients aged ≥18 with any form of CA (identified via ICD-9-CM codes) were included. Primary outcomes included the physical and mental component scores (PCS and MCS) of the Short-Form 12 version 2 (SF-12) and EuroQoL-5D (EQ-5D) utility scores (US version). Patient demographics included insurance status, urban status, geographical region, federal poverty level, education, comorbidities, and disease-related risk factors of CA. RESULTS: Approximately 5,750,440 individuals had CA. Non-Hispanic Whites had the highest SF-12 MCS (mean 50.9; p < 0.001 across racial groups) and utility scores (mean 0.76; p < 0.001 across racial groups). Patients with both private and public insurance had significantly higher PCS (p = 0.001) and MCS (p < 0.001) in comparison with patients only covered by public insurance. Patients on antiarrhythmic agents had higher SF-12 MCS (51.4 vs. 48.4; p < 0.001) compared to individuals not on antiarrhythmic agents. CONCLUSIONS: Significantly lower QOL existed in specific subpopulations (e.g., patients with only public health insurance, racial/ethnic minorities, and those not exposed to antiarrhythmic agents) within the CA population.

Cost-effectiveness of biological agents used in ulcerative colitis.

Ulcerative colitis (UC) produces bloody diarrhoea, severe abdominal pain, and need for clinic visits, hospitalizations, and surgeries. UC results in reduced health-related quality of life for patients and large direct medical and indirect costs for health systems and employers. Patients with the most severe disease require the most medical services, and these patients have larger costs than patients with mild or moderate disease. Despite biological therapies being quite expensive, they are indicated for patients unresponsive to initial standard therapies. Future hospitalizations may be reduced by starting a biological treatment. Cost-effectiveness results vary between countries, health systems, and model designs. Since restorative proctocolectomy can be curative, this surgery dominates biological therapy by being both less costly and more effective when measuring health system costs and patient quality-adjusted life years for 20 years. However the dose, duration, and effectiveness of biological treatments significantly impact estimates of their cost-effectiveness.