A Budget Impact Model of Maintenance Treatment of Chronic Inflammatory Demyelinating Polyneuropathy with IgPro20 (Hizentra) Relative to Intravenous Immunoglobulin in the United States.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, progressive autoimmune disease causing peripheral nervous system dysfunction. Guidelines recommend immunoglobulin (IG) therapy as an immunomodulatory agent in CIDP. Drawbacks and unmet needs with intravenous immunoglobulin (IVIG) include adverse effects and wear-off effects, along with the burden of administration based on site of care. Subcutaneous administration of Hizentra, a subcutaneous immunoglobulin (SCIG) reduces patient burden by allowing self-administration outside the hospital setting and has fewer adverse events (AEs). OBJECTIVE: We aimed to compare the expected cost of treatment and the budget impact of Hizentra compared with IVIG for maintenance treatment of CIDP in the United States. METHODS: A decision tree model was developed to estimate the expected budget impact of maintenance treatment with Hizentra for US stakeholders. The model adopts primarily a US integrated delivery network perspective and, secondarily, a commercial perspective over a 1-year time horizon. Pharmacy costs were based on a payment mix of average sales price (73%), wholesale acquisition cost (2%), and average wholesale price (25%). Costs in the model reflect 2022 US dollars. In accordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines and recommendations for budget impact modeling, no discounting was performed. The PATH clinical study of Hizentra maintenance in CIDP was used to determine clinical inputs for relapse rates at initial assessment (24 weeks) and at 52 weeks for Hizentra. The ICE clinical study of Gamunex maintenance in CIDP was the basis of relapse rates for Gamunex (and other IVIGs). Literature-based estimates were obtained for infusion costs by site of care, costs of IVIG infusion-related complications, and significant IVIG AE rates. Hizentra AE rates from the US Hizentra prescribing information were assessed but were not included in the model as the AEs in CIDP were mild, easily treated, and self-limited. Sensitivity analyses and scenario analyses were conducted to evaluate variations from the base case. RESULTS: The model showed that a Hizentra starting dose of 0.2 g/kg is expected to result in annual cost savings of US$32,447 per patient compared with IVIG. For a hypothetical 25-million-member plan, the budget impact of a 10% market share shift from IVIG to Hizentra is expected to result in savings of US$2,296,235. CONCLUSION: This analysis projects that Hizentra is likely associated with favorable economic benefit compared with IVIG in managing CIDP.

Immunoglobulin replacement therapy in patients with immunodeficiencies: impact of infusion method on patient-reported outcomes.

BACKGROUND: Understanding the impact of different immunoglobulin (Ig) infusion methods (intravenous [IVIg] and subcutaneous [SCIg]) upon treatment experience can potentially facilitate optimization of patient outcomes. Here, the perspective of patients with primary and secondary immunodeficiency diseases (PID and SID, respectively) receiving IVIg and SCIg was evaluated, in terms of treatment satisfaction, accounting for treatment history, using Association des Patients Immunodéficients du Québec (APIQ) survey data. METHODS: The online APIQ survey (shared October 2020-March 2021) of patients with immunodeficiencies in Canada contained 101 questions on: Ig use, history, and detailed infusion characteristics; as well as structured patient-reported outcomes such as treatment satisfaction (via TSQM-9), symptom state (via PASS), general health perception (via GHP), and physical and mental function (via PROMIS). Adult respondents (≥ 18 years old) currently using Ig were compared by their current Ig infusion method (IVIg or SCIg cohort) overall, and in a sub-analysis, the IVIg cohort was compared with the SCIg cohort after stratification by respondents who started SCIg when naïve to Ig ('SCIg naïve') or with previous IVIg experience ('SCIg switch'). RESULTS: In total, 54 respondents currently used IVIg and 242 used SCIg. The average duration per infusion of a weekly SCIg infusion was significantly shorter compared with the average duration of a 3-4 weekly IVIg infusion (p < 0.001). The SCIg cohort was associated with significantly higher scores for the TSQM-9 effectiveness domain compared with the IVIg cohort. The scores for TSQM-9 convenience and global satisfaction domains were similar in the two cohorts. The SCIg cohort was also associated with a significantly higher proportion of respondents who were in an acceptable symptom state and a lower proportion who reported very poor or poor perception of health compared with the IVIg cohort. Further, the SCIg naïve subgroup was associated with significantly higher TSQM-9 effectiveness and convenience domain scores compared with the IVIg cohort, while there was no significant difference between the SCIg switch subgroup and the IVIg cohort in terms of convenience. CONCLUSIONS: A better understanding of how different IgRT administration methods impact treatment experience and satisfaction may assist with informed treatment decision making and ultimately further improvements in patient outcomes.

Reduced risk of infections with the intravenous immunoglobulin, IgPro10, in patients at risk of secondary immunodeficiency-related infections.

Aim: Patients with secondary immunodeficiency (SID) are at increased risk of infections and may be treated with immunoglobulin replacement therapy (IgRT). Despite growing efficacy evidence for IgRT in infection prevention in SID, treatment guidelines are not aligned. Materials & methods: A retrospective database analysis was conducted to assess treatment patterns and infection rates in patients at risk of SID-related infections, with or without IgRT (IgPro10) exposure, to evaluate real-world effectiveness of IgRT in infection prevention. Results: Of 11,448 patients included, 222 received IgPro10. B-cell malignancies and solid organ transplants were the predominant underlying conditions. Despite being sicker at baseline, the IgPro10 cohort demonstrated fewer infections post-index than the non-IgRT cohort. Conclusion: IgPro10 may be an effective option for infection prevention in SID.

Secondary immunodeficiency (SID) occurs when the immune system is weakened by external factors, including certain medical treatments. It can leave a person with an increased risk of potentially serious or even fatal infections, as they no longer have adequate defenses against bacteria. Some patients with this condition require treatment to boost their immune system, including supplementation of their antibodies, known as immunoglobulin replacement therapy (IgRT). In this study, we explored whether: (1) patients with conditions that are at risk of SID and associated infections received IgRT; and (2) whether receiving the IgRT reduced the incidence of infections. We found that patients who had IgRT were much less likely to experience infections than those who did not receive IgRT, suggesting that IgRT may be an effective treatment option for preventing infections in patients with compromised immune systems caused by SID.

Risk factors for severe infections in secondary immunodeficiency: a retrospective US administrative claims study in patients with hematological malignancies.

Real-world data are lacking to identify patients with secondary immunodeficiency (SID) who may benefit most from anti-infective interventions. This retrospective analysis used the IQVIA PharMetrics® Plus database to assess baseline characteristics associated with risk of severe infections post-SID diagnosis in patients with hematological malignancies. In 4066 patients included, the mean number of any and severe infections per patient in the one-year pre-SID diagnosis period was 9.5 and 0.7, respectively. Post-SID diagnosis, the mean annualized number of any and severe infections was 19.1 and 1.5, respectively. Receiver operating characteristic curve analysis identified a threshold (cutoff) of three bacterial infections at baseline as optimally predictive of severe infections post-SID diagnosis. Multivariate analysis indicated that hospitalizations, infections (≥3), or antibiotic use pre-SID diagnosis were predictive of severe infections post-SID diagnosis. Evaluation of these risk factors could inform clinical decisions regarding which patients may benefit from prophylactic anti-infective treatment, including immunoglobulin replacement if warranted.

Infections in secondary immunodeficiency patients treated with Privigen® or Hizentra®: a retrospective US administrative claims study in patients with hematological malignancies.

B cell-derived lymphoproliferative disorders are associated with secondary immunodeficiency (SID); some patients require immunoglobulin replacement therapy (IgRT) to mitigate infections. Using IQVIA's PharMetrics® Plus database, patients with SID who received IgPro10/IgPro20 in the 12 months post-diagnosis (IgRT users) were matched to patients with SID not receiving IgRT (non-IgRT users). The risk of severe infection was compared using within-patient change from baseline to follow-up as well as between cohorts. Overall, 277 IgRT users were matched to 1019 non-IgRT users. Before IgRT, more IgRT users experienced any bacterial infection (88.4% vs. 72.9%; p<.0001) or ≥1 severe bacterial infection (SBI) (42.2% vs. 31.8%; p=.0011) vs. non-IgRT users. During follow-up, risk of SBI among IgRT users (21.7%) reached parity with non-IgRT users (21.2%). IgRT was associated with a reduction in SBIs to levels comparable with the lower 'baseline infection risk' of non-IgRT users. These criteria help define SID patients who may benefit from IgRT.

Treatment Satisfaction with Subcutaneous Immunoglobulin Replacement Therapy in Patients with Primary Immunodeficiency: a Pooled Analysis of Six Hizentra® Studies.

PURPOSE: Primary immunodeficiency diseases (PIDDs) are a heterogenous group of disorders characterized by intrinsic impairment in the immune system. Most patients with PIDD require life-long immunoglobulin G replacement therapy, which has been shown to reduce the rate of infections and, related hospitalizations and reduce health-related quality of life (HRQOL). Here, treatment satisfaction and HRQOL in patients with PIDD was evaluated upon switching from intravenous (IVIG) or subcutaneous immunoglobulins (SCIGs) to 20% SCIG (Hizentra®), and during long-term steady-state Hizentra® treatment. METHODS: Analyses were based on two pivotal (switch) and four extension/follow-up (maintenance) Phase III studies of Hizentra® conducted in Europe (EU), Japan (JP), and the United States (US). Two validated questionnaires were used: Life Quality Index (LQI) for assessment of IgG-specific perceptions of HRQOL and Short Form 36 version 2 (SF-36v2). RESULTS: In the EU and JP switch studies, there was significant and meaningful improvement from Screening in LQI domain scores at all time points, largely driven by patients switching from IVIG to SCIG. In the EU switch study, there were also significant increases in mean SF-36v2 domain scores for Physical Function and General Health from Screening to Week 12. These improvements were observed also at Week 24. Overall, LQI and SF-36v2 domain scores were generally sustained in the maintenance studies. CONCLUSIONS: These results showed that switching patients from IVIG to SCIG improves patient self-reported health status and IgG-specific HRQOL perception. The maintenance studies generally showed no deterioration of this improved health status over a long follow-up period.

Hemolytic adverse effects of intravenous immunoglobulin: modeling predicts risk reduction with anti-A/B immunoaffinity chromatography and to a lesser extent with anti-A donor screening.

BACKGROUND: The risk of hemolytic events (HEs) with intravenous immunoglobulin (IVIG) therapy appears to be linked to isoagglutinins (anti-A and anti-B) in the product. Patient risk factors include high IVIG dose, blood group, and underlying inflammatory state. STUDY DESIGN AND METHODS: Using published anti-A and anti-B titers for IVIG products and HE rates calculated from HEs spontaneously reported to EudraVigilance, regression models were developed to infer the relationship between HE risk and IVIG isoagglutinin levels for each blood group. Applying estimated model coefficients to isoagglutinin levels associated with an IVIG (Privigen; CSL Behring, King of Prussia, PA), manufactured with and without isoagglutinin reduction steps, predicted HE risk values were generated for each product: 1) without any isoagglutinin reduction, 2) anti-A donor screening, and 3) anti-A/anti-B specific immunoaffinity chromatography (IAC; Ig IsoLo). RESULTS: Predicted HE risk was highest for blood group AB, followed by A and B; it was low for O. Projected population shares of HEs by blood group were similar to reported real-world data. Compared with the original process (no isoagglutinin reduction), the model predicts lower hemolytic risk with anti-A donor screening and even lower hemolytic risk with IAC isoagglutinin reduction. CONCLUSION: IAC isoagglutinin reduction is predicted to reduce the HE risk with IVIG substantially. Physicians should be especially vigilant to HE risk in patients with blood group AB and, to a lesser extent, A when using IVIG products with high anti-A titers.

The economic burden of CIDP in the United States: A case-control study.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare neurological disorder of the peripheral nervous system. The economic burden of CIDP is not well understood. OBJECTIVES: To assess the economic and clinical burden of CIDP and to compare the incremental burden relative to a matched control group without CIDP. METHODS: This retrospective case-control analysis was conducted using data from the IQVIA Real-World Data Adjudicated Claims. Adults newly diagnosed with CIDP between 7/1/2010 and 6/30/2014 were identified and direct matched to controls without CIDP. Baseline characteristics were assessed and compared over a 6-month pre-index period. Healthcare resource use, costs and clinical characteristics were assessed and compared over a 2-year follow-up. Total cost differences over the 2-year follow-up were compared between matched cohorts using a generalized estimating equation model. RESULTS: The final sample comprised a total of 790 cases matched to 790 controls. Over the 2-year follow-up, cases more frequently experienced neuropathic pain, back pain and osteoarthritis and more commonly utilized opioids, anti-convulsants and anti-depressants. Compared to controls, more cases had ≥1 hospitalization (26.2% vs. 9.0%), and cases had a higher mean number of outpatient prescription fills (62.8 vs. 32.0) and physician office visits (34.7 vs. 13.0) (all p<0.0001). Cases had 7.5x higher mean total costs ($116,330 vs. $15,586, p<0.0001). Important cost drivers were costs for outpatient ancillary, radiology and HCPCS drugs (mean $76,366 vs. $4,292) and costs for inpatient care (mean $16,357 vs. $2,862) (both p<0.0001). Among cases, CIDP therapy (inclusive of both outpatient pharmacy and medical claims) accounted for 51.2% of mean total costs. After further adjusting for baseline clinical characteristics, cases were associated with a 6.1x increase in total costs compared to controls (p<0.0001). CONCLUSIONS: Our findings suggest a substantial clinical and economic burden among patients with CIDP relative to matched controls over a 2-year follow-up.

Relationship between patient-reported symptoms, limitations in daily activities, and psychological impact in varicose veins.

OBJECTIVE: The objective of this study was to evaluate the relationship between patient-reported symptoms, functional limitations, and psychological impact of varicose veins (VVs) vs pathophysiologic mechanism, incorporating demographic and behavioral factors. METHODS: We conducted a pooled analysis from two clinical studies (Efficacy and Safety Study of Polidocanol Injectable Foam for the Treatment of Saphenofemoral Junction Incompetence [VANISH-1] and Polidocanol Endovenous Microfoam Versus Vehicle for the Treatment of Saphenofemoral Junction Incompetence [VANISH-2]) in patients with VVs (superficial venous reflux only). Health outcomes were classified on the basis of the Wilson-Cleary conceptual framework continuum linking clinical and anatomic factors (Clinical, Etiology, Anatomy, and Pathophysiology [CEAP] clinical class and great saphenous vein [GSV] diameter, respectively) to patient-reported outcomes: Varicose Vein Symptoms Questionnaire (VVSymQ) score; modified Venous Insufficiency Epidemiologic and Economic Study on Quality of Life/Symptoms (m-VEINES-QOL/Sym) limitations in daily activities (functional limitations hereafter) score; and m-VEINES-QOL/Sym psychological impact score. Association of clinical and anatomic categories with each of the patient-reported outcomes was assessed using analysis of variance for statistical significance and standardized mean differences for clinical meaningfulness. Hierarchical regression modeling was applied to evaluate the direct association of the VVSymQ symptom score with the m-VEINES-QOL/Sym functional limitations score and the indirect association with the m-VEINES-QOL/Sym psychological impact score, adjusting for clinical, behavioral, and demographic factors. RESULTS: Among 516 patients, approximately three-fourths were women (mean age, 49 years), approximately 70% were overweight or obese, 42% were C2 and 32% were C3, and 88% reported never or only intermittently wearing compression stockings. VVSymQ (symptom) scores did not vary by GSV diameter but were significantly worse for those with severe disease stage, especially C5 or C6. Among m-VEINES-QOL/Sym work-related function items, 47% of patients reported difficulty at work and 31% reported cutting down at work. On nonwork function items, standing for prolonged periods was most affected; 53% were limited a little and 22% were limited a lot. Concern about appearance and choice of clothing predominated among psychological impact items, with 74% and 65%, respectively, affected all or most of the time. The m-VEINES-QOL/Sym functional limitation and psychological impact scores varied by neither GSV diameter nor CEAP C class, but they varied directly with VVSymQ (symptom) score quartiles. Multivariable regression analysis revealed that VVSymQ symptom scores continued to be associated with m-VEINES-QOL/Sym psychological impact scores, even after adjustment for m-VEINES-QOL/Sym functional limitation scores. CONCLUSIONS: Substantial patient-reported functional limitation and psychological impact of VVs were observed. Limitations on work, standing for prolonged periods, concern about appearance, and clothing choice were most affected. Patient-reported VVSymQ (symptom) score, an objective patient-reported measure of symptom severity in VVs, was the key predictor of patient-reported m-VEINES-QOL/Sym functional limitations. Symptoms and functional limitations led to greater psychological impact. Physicians should routinely ascertain symptoms and functional limitations to enhance quality of care and to document medical necessity.

Improvement in patient-reported outcomes of varicose veins following treatment with polidocanol endovenous microfoam.

Objective To evaluate the relationship between patient-reported symptoms and functional and psychological impact of varicose veins following treatment with polidocanol endovenous microfoam (PEM) 1%. Methods Data were pooled from two randomized trials on VV treatment. Wilson-Cleary health outcomes path model was applied to evaluate impact of VVSymQ™ symptom score improvement on modified VEINES-QOL/Sym functional and psychological scores. Change scores were evaluated for (i) PEM 1% versus placebo groups and (ii) quartiles of symptom improvement. Cumulative distribution function curves were generated to compare percentage of patients with various levels of functional and psychological improvement including clinically meaningful improvement across two treatment groups. Multivariable regression models of change scores and clinically meaningful changes were estimated. Results In 221 patients (109 PEM 1%; 112 placebo), PEM 1% was associated with median improvements of 2.5 points and 4.0 points on the m-VEINES-QOL/Sym functional limitations and m-VEINES-QOL/Sym psychological limitations scores, compared to 0 and 1.0 point improvements, respectively, for placebo. Cumulative distribution function curves revealed that 20-30% more patients in PEM 1% group achieved clinically meaningful functional and psychological improvement versus placebo group. Conclusions Patients with above-average symptom improvement had better functional and psychological improvement. PEM 1% treatment had higher odds of clinically meaningful functional and psychological improvement.

Real-World Assessment of Interventional Treatment Timing and Outcomes for Varicose Veins: A Retrospective Claims Analysis.

PURPOSE: To evaluate the impact of delaying interventional treatment on varicose vein disease progression, complications, and health care costs in a real-world setting. MATERIALS AND METHODS: This was a retrospective analysis of adults diagnosed with varicose veins between January 2008 and June 2010. Patients were followed for 2 years after diagnosis and categorized into three cohorts based on the timing of interventional therapy: early (≤ 2 mo), intermediate (> 2 mo but ≤ 6 mo), and late (> 6 mo). Disease progression and all-cause health care costs were evaluated. RESULTS: A total of 44,206 patients were included, with 43% classified as receiving early interventional therapy, 33% as intermediate, and 24% as late. Early interventional treatment was associated with lower disease progression rates (29.2%) compared with intermediate (42.5%; P < .0001) and late treatment (52.2%; P < .0001). Also, early interventional treatment was associated with lower costs ($17,564) than intermediate ($17,923; P > .05) and late treatment ($18,399; P < .05). Each 30-day delay in treatment initiation was associated with a 7% higher risk of disease progression (P < .0001) and a 1% increase in costs (P < .0001). CONCLUSIONS: Findings suggest that early initiation of interventional varicose vein treatment was significantly associated with a decreased risk of disease progression and costs.

Treatment Patterns and Outcomes in Patients with Varicose Veins.

BACKGROUND: Approximately 24% of adults in the United States have visible varicose veins, and an estimated 6% have evidence of advanced chronic venous disease. The majority of individuals with varicose veins seek treatment because of symptoms, such as aching, throbbing, fatigue, pruritus, ankle swelling, and tenderness, rather than cosmetic reasons. Furthermore, varicose veins are a manifestation of chronic venous insufficiency, which can progress to leg pain, leg edema, chronic skin changes, and nonhealing ulcers. OBJECTIVE: To assess varicose vein treatment patterns and their corresponding outcomes, including additional treatment rates, disease progression to new ulcers, and associated costs from a US perspective. METHODS: We conducted a retrospective claims database study using data from the Truven Health MarketScan database. Adults who were newly diagnosed with varicose veins between January 1, 2008, and June 30, 2010, and met the study inclusion criteria were eligible to participate and were divided into 6 cohorts based on the type of first or initial therapy they received after the index diagnosis date, including surveillance and compression therapy, surgery, laser ablation, radiofrequency ablation, sclerotherapy, or multiple therapies. The patients were followed for 2 years after the index diagnosis date to assess their treatment patterns and outcomes. RESULTS: A total of 144,098 patients met the study criteria. Of these patients, 100,072 (69.5%) were under surveillance for disease progression and/or received compression therapy; 14,007 (9.7%) received laser ablation; 9125 (6.3%) received radiofrequency ablation; 4778 (3.3%) received sclerotherapy; 4851 (3.4%) had surgery; and 11,265 (7.8%) received multiple therapies. During the 2-year follow-up period, among patients receiving interventional treatment, 54.7% of patients received additional interventional treatment (either with the same mode or a different mode from the initial treatment); 30.1% had >1 postintervention claim for symptomatic varicose veins (not including additional procedures) at 8 weeks; and 44.2% had >1 postintervention claim for symptomatic varicose veins at 1 year after the initial interventional therapy. CONCLUSIONS: A majority of the patients in the study received conservative management. For patients receiving interventional therapy, the outcomes varied based on the treatment cohort. The surgery cohort was associated with the most favorable outcome regarding the need for additional treatment and evidence of postintervention claims for symptomatic varicose veins, followed by the multiple therapies cohort. A better understanding of these treatment outcomes in the real-world setting may affect new strategies to improve the management of patients with varicose veins.

Evaluating the Expected Costs and Budget Impact of Interventional Therapies for the Treatment of Chronic Venous Disease.

BACKGROUND: Chronic venous disease is a common disorder in the United States. The manifestations of chronic venous disease include varicosities and related sequelae that are frequent contributors to the morbidity and high costs associated with the disease. The interventional treatment options for chronic venous disease have expanded greatly in recent years and include various surgical and vein ablation techniques. Polidocanol injectable foam (also known as polidocanol endovenous microfoam 1%), a chemical ablation agent, is the most recent entrant to the market. OBJECTIVE: To evaluate the expected patient-level total treatment costs and health plan-level budgetary impact of polidocanol injectable foam compared with the currently available interventional treatment options from a third-party US payer perspective. METHODS: A Microsoft Excel-based budget impact model was designed to compare the costs of polidocanol injectable foam with other interventional treatments (ie, laser ablation, radiofrequency ablation, surgery, and multimodality treatment). The model included drug acquisition, medical procedure, administration, additional treatment, and disease progression costs. The treatment patterns and rates of additional treatment were incorporated from a recent retrospective claims analysis for established treatment modalities and from the clinical trials for polidocanol injectable foam. The model estimates the 1-year total estimated costs and the health plan budget impact assuming an 8-week treatment time frame. RESULTS: The total expected 8-week treatment costs were $2165 for polidocanol injectable foam, $1827 for endovenous laser ablation, $2106 for radiofrequency ablation, $2374 for surgery, and $2844 for multimodality treatment. The initial treatment costs were higher for surgery and multimodality treatment compared with polidocanol injectable foam and were lower for endovenous laser ablation and radiofrequency ablation treatments. Polidocanol injectable foam is projected to have a relatively small budget impact ($0.01 per member per month) at an initial 5% market share. CONCLUSION: Polidocanol injectable foam offers an alternative to other interventional options for the treatment of varicose veins and is projected to have a relatively small budget impact. From a health plan perspective, this drug is likely to have a relatively low budget impact as it becomes more widely used.

Cholesterol treatment patterns and cardiovascular clinical outcomes associated with colesevelam HCl and ezetimibe.

INTRODUCTION: Pharmaceuticals are commonly used to help at-risk patients reduce low-density lipoprotein cholesterol (LDL-C) levels in an effort to prevent atherosclerotic coronary artery disease. Although both the cholesterol inhibitor ezetimibe and the newer generation bile acid sequestrant colesevelam hydrochloride (HCl) effectively reduce LDL-C levels in patients with hypercholesterolemia, real-world evidence based on clinical outcomes is lacking. METHODS: A retrospective analysis of healthcare insurance claims data from a large national healthcare payer was conducted to evaluate outcomes within 12 months among 2,067 patients with hypercholesterolemia after the initiation of treatment with colesevelam HCl (679 patients) as compared with ezetimibe (1,388 patients). Outcomes evaluated were (1) composite cardiovascular event which included myocardial infarction, stroke, angina, or revascularization and (2) macrovascular complication event which was a wider-encompassing measure that included all composite cardiovascular outcomes along with atherosclerosis, aneurysm, embolism, and peripheral vascular disease. RESULTS: An adjusted logistic regression model found lower odds of a composite cardiovascular event (odds ratio [OR] 0.54, 95 % confidence interval [CI] 0.30-0.97) within 12 months for subjects initiating treatment with colesevelam HCl compared with subjects initiating treatment with ezetimibe. The unadjusted OR was slightly lower (OR 0.52, 95 % CI 0.30-0.90). The odds ratio for the wider-encompassing macrovascular complication event occurring within 12 months of initiating treatment with colesevelam HCl or ezetimibe was not statistically significant (OR 0.821, 95 % CI 0.49-1.35). DISCUSSION: The evidence of lower risk for composite cardiovascular event rates for subjects treated with colesevelam HCl compared with those treated with ezetimibe suggests the potential need to consider risk of clinical outcomes, in addition to LDL-C levels, in real-world practice when choosing a pharmaceutical treatment.

Understanding the experience of living with non-small-cell lung cancer (NSCLC): a qualitative study.

BACKGROUND: As non-small-cell lung cancer (NSCLC) treatments improve and patients live longer, it is important to develop interventions to help patients live fuller lives. We sought to identify key components of quality of life (QOL) in determining therapeutic decision making and overall value of life extension in patients with NSCLC. METHODS: Three focus groups (n = 16) and telephone interviews (n = 15) were conducted with NSCLC patients (N = 31) to explore symptoms considered important to QOL. A trade-off format was used to assess the value of life extension relative to QOL. Patients were asked to consider a hypothetical treatment option offering a modest (3 month) life extension. RESULTS: Patients' mean age was 61.6 years, 67.6% were women, 77.4% were white, and 48.4% had stage III/IV disease. In all, 68% of patients conceptualized emotions as symptoms of NSCLC. Key symptoms changed over time: Patients reported feeling shock and fear at diagnosis (74%), and feeling fear or loneliness during the beginning of therapy (55%). Additionally, patients who reported successfully connecting with other NSCLC patients (peers), support groups, and/or community members reported a positive shift in feelings (52%) as they continued therapy or moved into a posttherapy phase. Financially, 23% of patients reported being adversely affected by copayments, 36% by unexpected gaps in coverage, and 39% by other bills. Patients reported that the most important dimension driving their decision making about life-extending therapy was somatic (84%), followed by functional (32%), relational (23%), and emotional (10%) dimensions. LIMITATIONS: Study participants were likely to have received some education or support from the recruiting cancer advocacy and patient education/support organizations. In addition, participants were of a higher socioeconomic status than the average lung cancer patient population. CONCLUSIONS: Patients with NSCLC conflated emotional well-being after diagnosis with symptoms of their cancer and treatment toxicities. Somatic QOL concerns emerged ahead of functional, emotional, and relational QOL concerns as the dominant driver of therapeutic decision making. FUNDING: This study was funded by Daiichi Sankyo Inc.

Colesevelam, Ezetimibe, and Patients With Type 2 Diabetes Mellitus: Characteristics and Clinical Outcomes From a Health Care Database.

BACKGROUND: Despite the prevalence of therapies available to patients at highest coronary heart disease risk, only a minority of type 2 diabetes mellitus (T2DM) patients reach desired cholesterol treatment levels, with limited data regarding their outcomes. OBJECTIVE: To examine "real-world" effectiveness of initiating treatment with either colesevelam or ezetimibe among individuals with evidence of T2DM and hypercholesterolemia (HCh). Key outcomes included treatment patterns and cardiovascular (CV) events. METHODS: This retrospective administrative claims-based study utilized medical, pharmacy, and enrollment data linked to laboratory results information from a large United States health plan (January 1, 2006, to March 31, 2011) and included individuals with recorded evidence of T2DM and HCh. The index date was the date of first pharmacy claim for colesevelam or ezetimibe, with cohort assignment based on index medication. Assessments included baseline characteristics, follow-up treatment patterns, and composite CV event, with propensity score matching to correct for sample selection bias. RESULTS: In total, 4231 individuals were identified with evidence of HCh and T2DM (ezetimibe n = 3384; colesevelam n = 847). After matching, the baseline characteristics between cohorts were rendered to be similar. Mean days of persistent medication use was lower with colesevelam compared with ezetimibe (P < 0.001). Compared with ezetimibe, a smaller percentage of individuals in the colesevelam cohort experienced a follow-up composite CV event, and adjusted Cox model results suggested decreased risk (hazard ratio = 0.58; P = 0.004) of a follow-up composite CV event. CONCLUSION: In this health care database analysis among patients with HCh and T2DM, colesevelam was associated with decreased risk of a composite CV event compared with ezetimibe, despite lower persistence.

Psychometric properties of a brief, clinically relevant measure of pain in patients with hepatocellular carcinoma.

PURPOSE: Due to diagnosis at advanced stages, comorbidities, and the impact of treatment, patients with hepatocellular carcinoma (HCC) may experience pain. The purpose of this study was to evaluate the psychometric properties of a brief, clinically relevant measure of pain in HCC. METHODS: We conducted a secondary data analysis from four longitudinal studies of patients with HCC (total n = 304). All patients completed the FACT-Hepatobiliary (FACT-Hep) questionnaire, and 49 patients completed the Brief Pain Inventory (BPI) Interference scale. We conducted confirmatory factor analysis (CFA), Rasch modeling, and correlational analysis to assess the psychometrics of the three items on the FACT-Hep that assess HCC-relevant pain scale. RESULTS: Patients had an average age of 63.5 (±12.2) and were mostly male (76 %). The mean three-item pain subscale score was 8.5 ± 3.0. Seventy-four (24.3 %) patients reported no pain (score = 12). Results of a one-factor CFA supported unidimensionality of the items, and all items fit the Rasch model. An item-person map demonstrated that the three items covered all patients with non-extreme scores. Pain scores were significantly associated with baseline general health-related quality of life (FACT-General, r = 0.60, p < 0.001) and pain interference (BPI, r = -0.63, p < 0.001). CONCLUSIONS: The three FACT-Hep pain items are unidimensional, cover the range of pain experienced by most patients with HCC, and demonstrate convergent validity. This pain subscale is, if future research demonstrates its sensitivity to change, potentially useful for HCC clinical trials.

Important and relevant symptoms including pain concerns in hepatocellular carcinoma (HCC): a patient interview study.

PURPOSE: We examined the health-related quality of life (HRQOL) and pain experiences of patients with hepatocellular carcinoma (HCC) and assessed content validity of existing patient-reported pain items for patients with HCC. METHODS: Semi-structured interviews to elicit symptoms, side effects and concerns were conducted with ten patients with HCC. Symptom and side effect importance was ranked on a 0 to 10 scale. Patients completed pain items from the Functional Assessment of Cancer Therapy--Hepatocellular (FACT-Hep) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire--Hepatocellular-18 (EORTC QLQ-HCC18). RESULTS: Mean age was 58 years (range 33-77). Spontaneously reported symptoms included fatigue (n = 5), diarrhea (n = 5), skin toxicities (n = 5), and loss of appetite (n = 4). Upon questioning, nine of ten patients reported experiencing pain over the course of their treatment. Over half of the importance rankings given for pain were 8 or higher on a 0 to 10 scale. Abdomen (n = 7) and lower back (n = 3) were the most common sites of pain. Pain onset varied from 6 months pre-diagnosis to over 2 years post-diagnosis. All patients indicated that FACT-Hep and EORTC items adequately assessed their pain. CONCLUSIONS: Results support the content validity of FACT-Hep pain items for patients with HCC. The finding that patients typically did not spontaneously report pain but often ranked it as very important for their HRQOL upon questioning suggests a need for systematic, routine pain and other symptom assessment and management as an integral component of patient care in advanced HCC.

Predictors of non-adherence to systemic oral therapy for advanced hepatocellular carcinoma.

OBJECTIVES: With increasing use and cost of oral oncology medications, patient non-adherence with oral therapy is of concern. This study evaluated non-adherence among patients receiving first-line oral therapy for hepatocellular carcinoma (HCC). METHODS: This retrospective study used the employer-based MarketScan medical and pharmacy claims database (2005-2011) to identify adult patients with two or more diagnoses of HCC (ICD-9 155), and two or more filled prescriptions for sorafenib. Additional eligibility requirements were not having other previous cancers and a 4 month wash-out period prior to the index sorafenib date. Adherence was assessed using a modified proportion of days covered (PDC) measure with patient-specific sorafenib exposure from index date to treatment discontinuation. Non-adherence was categorized as PDC <85% (base case), with sensitivity analyses using an 80% cut-off and allowance for physician-directed therapy gaps. Logistic regression models were estimated to identify predictors of non-adherence. RESULTS: A total of 1127 patients (median age = 61.0 years; 78.4% male) met eligibility criteria. Median duration of enrollment was 223 days and median sorafenib exposure was 121 days. Between 21.1% (PDC < 0.80) and 28.0% (PDC < 0.85) of patients were non-adherent. Higher age (p = 0.022), number of baseline medications (p = 0.003) and number of baseline comorbidities (p = 0.002) were associated with lower non-adherence, while prior procedures were associated with greater non-adherence (p = 0.002). LIMITATIONS: In this study using billing claims data, we were unable to evaluate patient severity in terms of clinical characteristics such as the Child-Pugh score. Similarly, we could not assess clinical outcomes such as tumor response, radiological progression or overall survival, although median duration of sorafenib exposure and duration of health plan enrollment respectively were found to be good proxies. CONCLUSIONS: Using a modified PDC approach, 22-29% of patients were non-adherent. Identified predictors of non-adherence in HCC should be assessed for newly emerging oral therapies, and may be used to guide patient education and other adherence-enhancing initiatives.

Failure of surgical and endovascular infrainguinal and iliac procedures in the management of peripheral arterial disease using data from electronic medical records.

PURPOSE: To understand rates of procedure failure among patients undergoing revascularization for peripheral arterial disease (PAD) in clinical practice. MATERIALS AND METHODS: This retrospective analysis of patients with PAD who underwent a PAD-related procedure used claims and electronic medical record data from 2005 to 2009. Procedures were grouped by type (endovascular [ie, angioplasty with/without stent, atherectomy] or surgical [ie, bypass surgery, endarterectomy, thrombectomy]) and site (ie, iliac, infrainguinal). The study assessed antiplatelet and anticoagulant agent use; procedure failure, defined as a subsequent procedure or amputation; and predictors of time to procedure failure. RESULTS: A sample of 248 patients with PAD who underwent a PAD-related procedure was identified. The population was 59% male, had a mean age of 73 years, and had a mean follow-up of 23 months. Endovascular procedures alone were performed in 37% of patients, with the remainder receiving surgery only or surgery with an endovascular procedure, and 79% of patients had an infrainguinal intervention. Antiplatelet and anticoagulant use rates after the procedure were 90% and 25%, respectively. After their initial procedure, 20% of patients required a second procedure or amputation, with an average failure time of 228 days. Patients treated with infrainguinal procedures had a significantly higher failure rate versus those treated with iliac procedures (23% vs 8%; P = .011). In multivariate analysis, patients without anticoagulant use before the procedure were at significantly lower failure risk (P = .022). CONCLUSIONS: Repeated intervention and/or major amputation after revascularization of PAD was common. Further investigation of the factors associated with procedure failure is warranted.