Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa. METHODS: PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1:1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12. RESULTS: We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P<0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences. CONCLUSIONS: Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. (Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively.).

Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV infection and psychiatric disorders: An integrated analysis.

Although direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection are highly efficacious and safe, treatment initiation is often limited in patients with neuropsychiatric disorders due to concerns over reduced treatment adherence and drug-drug interactions. Here, we report adherence, efficacy, safety and patient-reported outcomes (PROs) from an integrated analysis of registrational studies using the pangenotypic DAA regimen of glecaprevir and pibrentasvir (G/P). Patients with chronic HCV genotypes 1-6 infection with compensated liver disease (with or without cirrhosis) receiving G/P for 8, 12 or 16 weeks were included in this analysis. Patients were classified as having a psychiatric disorder based on medical history and/or co-medications. Primary analyses assessed treatment adherence, efficacy (sustained virologic response at post-treatment week 12; SVR12), safety and PROs. Among 2522 patients receiving G/P, 789 (31%) had a psychiatric disorder with the most common diagnoses being depression (64%; 506/789) and anxiety disorders (27%; 216/789). Treatment adherence was comparably high (>95%) in patients with and without psychiatric disorders. SVR12 rates were 97.3% (768/789; 95% CI = 96.2-98.5) and 97.5% (1689/1733; 95% CI = 96.7-98.2) in patients with and without psychiatric disorders, respectively. Among patients with psychiatric disorders, SVR12 rates remained >96% by individual psychiatric diagnoses and co-medication classes. Overall, most adverse events (AEs) were mild-to-moderate in severity with serious AEs and AEs leading to G/P discontinuation occurring at similarly low rates in both patient populations. In conclusion, G/P treatment was highly efficacious, well-tolerated and demonstrated high adherence rates in patients with chronic HCV infection and psychiatric disorders.

Effect of ombitasvir/paritaprevir/ritonavir + dasabuvir regimen on health-related quality of life for patients with hepatitis C.

BACKGROUND & AIMS: This study analyses health-related quality of life data from 8 randomized clinical trials using ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin to investigate: (i) the impact of the treatment vs placebo during treatment on health-related quality of life; (ii) the sustainability of such treatment effect after 12-week treatment period; and (iii) if results from (i) and (ii) differ in subgenotypes 1a vs 1b. METHODS: Six registration trials and 2 post-approval trials were pooled and analysed using longitudinal mixed models to estimate the effect of ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin on health-related quality of life outcomes adjusting for baseline scores, as well as patient demographics and clinical characteristics. RESULTS: Patients treated with ribavirin-free ombitasvir/paritaprevir/ritonavir and dasabuvir regimen reported statistically significant increase in health-related quality of life outcomes as compared to placebo patients. While ombitasvir/paritaprevir/ritonavir and dasabuvir + ribavirin treatment saw statistically significant decline in health-related quality of life outcomes during treatment vs baseline and placebo, effect on health-related quality of life outcomes associated with ribavirin did not persist in the post-treatment period for ombitasvir/paritaprevir/ritonavir and dasabuvir patients followed for up to 52 weeks. The analysis also found Genotype 1b patients reported greater improvements in health-related quality of life as compared to genotype 1a patients. CONCLUSIONS: During the active treatment period, small but statistically significant decrements in health-related quality of life outcomes were observed potentially driven by ribavirin, which were not sustained during the post-treatment follow-up period. Differences were observed by patient subgenotype, where health-related quality of life improvements were consistently higher for genotype 1b patients as compared to genotype 1a patients.

Association of RSV-related hospitalization and non-compliance with palivizumab among commercially insured infants: a retrospective claims analysis.

BACKGROUND: Palivizumab has been shown to decrease the incidence of hospitalization due to respiratory syncytial virus (RSV) in infants at risk of severe RSV disease. We examined the association between compliance with palivizumab dosing throughout the RSV season and risk of RSV-related hospitalization in clinical practice. METHODS: Subjects who were born and discharged from the hospital before the RSV season and received ≥1 palivizumab dose during their first RSV season were identified from a large US commercial health insurance database between 01/01/03 and 12/31/09. Subjects were deemed compliant if they received ≥5 palivizumab doses without gaps (>35 days) and their first dose was received by November 30. RSV-related hospitalizations were identified using ICD-9-CM diagnosis codes and examined over 2 observation periods: post-index dose and RSV season. A Cox proportional hazard model was used to evaluate the association between non-compliance and RSV-related hospitalization. RESULTS: Of the 5,003 subjects who received palivizumab, 62% were deemed non-compliant. Non-compliant subjects had significantly higher unadjusted rates of RSV-related hospitalizations compared to compliant subjects during both observation periods (post-index: 6.1 vs. 2.8 per 100 infant seasons, p < 0.001; RSV season: 5.9% vs. 2.3%; p < 0.001). In multivariate analyses, non-compliance was significantly associated with higher risk of RSV-related hospitalization (HR = 2.01; p < 0.001). Of the 225 RSV-related hospitalizations observed during the RSV season, 61 (27%) occurred before the first dose of palivizumab. CONCLUSIONS: Subjects who did not receive monthly dosing of palivizumab throughout the RSV season had significantly higher rates of RSV-related hospitalizations. The RSV-related hospitalizations prior to the first dose of palivizumab suggest some dosing was started too late.

Low-Dose Elagolix for the Treatment of Heavy Menstrual Bleeding in Patients With Uterine Leiomyomas: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the safety and efficacy of elagolix 150 mg once-daily monotherapy in patients with heavy menstrual bleeding associated with uterine leiomyomas. METHODS: A phase 4, randomized, double-blind, placebo-controlled, 6-month treatment study was conducted in premenopausal patients aged 18-51 years with heavy menstrual bleeding (defined as menstrual blood loss greater than 80 mL during one menstrual cycle) associated with uterine leiomyomas. Patients were randomized 2:1 to receive elagolix 150 mg once daily or placebo. The primary endpoint was reduction in menstrual blood loss volume to less than 80 mL at the final month and at least a 50% reduction in menstrual blood loss volume from baseline to the final month. RESULTS: Of 82 randomized patients, 54 received elagolix 150 mg and 28 received placebo. With elagolix, 49.4% (95% CI 35.1-63.8%) of patients met the primary endpoint, compared with 23.3% (95% CI 7.2-39.5%) of patients who received placebo ( P =.035). Statistically significant differences between elagolix and placebo in mean reduction of menstrual blood loss from baseline were seen as early as month 1 ( P <.05 for months 1-3 and 5). Significantly more patients receiving elagolix experienced suppression of bleeding compared with placebo ( P =.036). Greater improvements were observed in the elagolix group (vs placebo) in the proportion of patients with amenorrhea, in hemoglobin concentrations, and in health-related quality of life. No serious or severe adverse events were reported for elagolix, compared with 7.1% of participants in the placebo group having serious adverse events (coronavirus disease 2019 [COVID-19] n=1, enlarged uvula n=1). Three patients (5.6%) discontinued elagolix due to adverse events. CONCLUSION: Elagolix 150 mg once-daily monotherapy significantly improved heavy menstrual bleeding associated with uterine leiomyomas compared with placebo in premenopausal patients. Treatment with elagolix 150 mg once daily was generally well-tolerated in this study, with no new safety signals. FUNDING SOURCE: AbbVie Inc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT03886220.

Factors related to immunosuppressant medication adherence in renal transplant recipients.

Non-adherence to immunosuppressant medications (ISM) is a significant issue for transplant recipients. This study examines factors influencing ISM adherence in renal transplant recipients (RTRs). Patient-reported data were collected through a cross-sectional survey including use of ISMs, adherence behaviors, perceived adherence barriers, beliefs and attitudes toward ISMs, and patient life satisfaction. Logistic regression was conducted to examine how RTRs' beliefs about use of ISMs, life satisfaction, and ISM adherence barriers were related to adherence. A total of 512 adult commercial insurance enrollees following renal transplantation were included in the analysis. One hundred and seventy-seven RTRs were non-adherent (34.5%); the most frequently cited reason was forgetfulness. RTRs aged 18-29 yr were more likely to be non-adherent than recipients 46-64 yr old (p ≤ 0.001). Non-adherent RTRs had greater adherence barriers than adherent RTRs (p < 0.001). Adherent RTRs believed their ISMs were more necessary than non-adherent RTRs (p < 0.001), while non-adherent RTRs had greater concerns about taking ISMs (p = 0.009) and believed they had less control over their lives than adherent RTRs (p < 0.001). Non-adherent RTRs had lower life satisfaction (p < 0.001). Non-adherence is significantly associated with patients' beliefs about ISMs, perceived barriers, and lower life satisfaction. Strategies to increase ISM adherence are discussed.

Hypothyroidism Prevalence in the United States: A Retrospective Study Combining National Health and Nutrition Examination Survey and Claims Data, 2009-2019.

Previous estimates determined prevalence of hypothyroidism (HT) to be 4.6% of the US population. This study aimed to update estimates of HT prevalence in the United States by retrospective analysis of 2 datasets. Data on HT type (overt or subclinical HT) and treatment were collected from the 2009-2010 and 2011-2012 National Health and Nutrition Examination Survey (NHANES) cycles. From the Optum administrative claims database, medical and pharmacy claims were collected between January 1, 2012, and December 31, 2019. Patients were defined as having HT if, per given year, they had >1 prescription for HT treatment, >1 claim indicating an HT diagnosis, or thyroid-stimulating hormone levels >4.0 mIU/L (NHANES arm). For both studies, treatment was defined as any evidence of synthetic or natural thyroid hormone replacement, identified by pharmacy claims or patient surveys. Data are reported as percentage of patients with HT and treatments received. Between 2009 and 2012, HT prevalence remained around 9.6% of the US population. The administrative claims dataset showed that HT prevalence grew from 9.5% in 2012 to 11.7% in 2019 and that >78% of patients received thyroxine (T4) monotherapy. Similarly, the NHANES dataset showed that T4 replacement therapy was the most common treatment for HT. From 2012-2019, patients with untreated HT grew from 11.8% to 14.4%. The prevalence of HT in the United States has steadily increased since 2009. Likewise, the percentage of hypothyroid-diagnosed patients not receiving treatment also increased, suggesting that the increased prevalence may be due to increased cases of subclinical HT.

Joint association of hyperuricemia and reduced GFR on cardiovascular morbidity: a historical cohort study based on laboratory and claims data from a national insurance provider.

BACKGROUND: Hyperuricemia is common in patients with chronic kidney disease (CKD). We assessed the relationship of increased serum uric acid levels with cardiovascular risk across levels of kidney function. STUDY DESIGN: Historical cohort study. SETTING & PARTICIPANTS: Study data were drawn from administrative records of a national private health insurer (2003-2006). We included all adult beneficiaries with concurrently measured serum creatinine and serum uric acid. Patients with acute kidney failure or undergoing renal replacement therapy at baseline were excluded. PREDICTORS: Serum uric acid concentration and estimated glomerular filtration rate (eGFR). OUTCOMES & MEASUREMENTS: Cardiovascular diagnoses (myocardial infarction, subacute coronary heart disease, heart failure, cerebrovascular disease, or peripheral arterial disease) ascertained from billing claims. Cox proportional hazard models were used to test the association of predictors with cardiovascular morbidity. Models were adjusted for sociodemographic characteristics, selected comorbid conditions, and laboratory results. RESULTS: In 148,217 eligible patients, mean eGFR was 84 mL/min/1.73 m(2) and the prevalence of CKD stages 3-5 was 6.0%. Hyperuricemia (serum uric acid >7 mg/dL) was found in 15.6% of patients. The 40-month cumulative incidence of cardiovascular events (mean follow-up, 15.3 months) was 8.1%. Cardiovascular risk was associated independently with uric acid level, and this association was stronger in patients with lower eGFRs. LIMITATIONS: Observational design, lack of information for mortality and potential confounders, single creatinine and uric acid assessment. CONCLUSIONS: Serum uric acid concentration was an independent correlate of cardiovascular morbidity, and this association was stronger in patients with severely decreased eGFR. This investigation provides a rationale for further study of serum uric acid-lowering interventions on cardiovascular risk in the general population and patients with CKD.

Lack of association between hepatitis C infection and chronic kidney disease.

BACKGROUND & AIMS: Chronic kidney disease (CKD) can have a negative impact on the natural history of hepatitis C virus infection (HCV) infection; patients with HCV and CKD often have adverse outcomes. We evaluated a large and geographically diverse group of patients to determine whether HCV status has an independent effect on the risk of developing CKD. METHODS: We conducted a cohort study of 167,569 patients included in a national health care claims database from January 1, 2003-December 31, 2006, with a mean follow-up of 25.3 months. We used multivariable logistic regression analyses to measure the independent effect of HCV status on the baseline prevalence of and progression to CKD (estimated glomerular filtration rate, <60 mL/min/1.73 m(2)). RESULTS: The baseline prevalence of CKD was similar in patients with versus those without HCV (5.3% vs 5.1%, P = .3). Similarly, among patients with preserved renal function at baseline (n = 82,629), there was no difference in the overall progression to CKD in patients with versus those without HCV (3.8% vs 3.5%, P = .1). HCV status was not associated with progression to CKD, even after adjusting for patient demographics, comorbidities, and use of relevant medications (odds ratio, 0.92; 95% confidence interval, 0.79-1.08). CONCLUSIONS: We found no association between HCV and risk of development of CKD. These data are relevant in counseling HCV patients regarding the impact of HCV on renal function.

Assessing Patient Preferences for Treatment Decisions for New Direct Acting Antiviral (DAA) Therapies for Chronic Hepatitis C Virus Infections.

INTRODUCTION: The new direct acting antiviral (DAA) therapies are able to effectively treat chronic hepatitis C (CHC). This study elicited the preferences of CHC patients for treatment attributes of new DAAs. METHODS: An online discrete choice experiment survey was designed to collect data from adult CHC patients in the USA, UK, France, Germany, Spain, and Italy. Patients were asked to choose from alternative hypothetical DAA options, defined by differing levels of nine attributes [i.e., treatment duration, tablet count and packaging, cure rate, required office visits when on treatment, modifications to statins or to proton pump inhibitors (PPIs), and risks of diarrhea, headache and nausea]. Logistic regression was used to assess preference for the treatment options. RESULTS: A total of 328 patients with CHC completed the survey (USA, n = 227; European countries, n = 101), with a mean age of 47.7 years (SD = 14.4) and an average 11.2 years since CHC diagnosis; 51% of patients were female. More than half (60%) of the patients had treatment for CHC. Patients significantly preferred a DAA regimen with higher cure rate, shorter treatment duration, lower risks of diarrhea, headache, and nausea (all p < 0.001), reduced need for office visits when on treatment (p = 0.044), and without requiring dose reduction or timing change in PPIs (p = 0.032). Tablet counts were not found to be statistically significant. CONCLUSION: Given the overall high cure rates of new DAAs, CHC patients' preferences for therapy may be influenced by treatment attributes other than cure rates and tolerability. Treatments that are more convenient and require less disruption to their daily life (e.g., shorter treatment duration, no modification in PPI use, and fewer office visits when on treatment) are important to patients with CHC and should be considered when making treatment decisions. FUNDING: AbbVie.

Increased risk of graft failure in kidney transplant recipients after a diagnosis of dyspepsia or gastroesophageal reflux disease.

BACKGROUND: Gastrointestinal complications are common in patients who undergo kidney transplantation and may affect posttransplant outcomes. We examined the incidence and predictors of gastroesophageal reflux disease (GERD) and dyspepsia and their associations with graft survival and mortality after transplant. METHODS: We examined United States Renal Data System data and Medicare billing claims to identify diagnoses of dyspepsia and GERD among Medicare beneficiaries transplanted in 1995-2002 (n=42,257). Among GERD cases, we identified patients with reflux esophagitis (RE). We determined independent predictors of upper gastrointestinal complications and modeled these conditions as time-dependent outcomes predictors with Cox regression. RESULTS: The 3-year cumulative incidences of GERD, RE, and dyspepsia were 20%, 5%, and 6%, respectively. Overall, 23% of transplant recipients received a diagnosis of at least one of these complications by 3 years after transplant. Female gender and a pretransplant upper gastrointestinal disease diagnosis predicted posttransplant gastrointestinal complications. Older age, obesity, Caucasian, and African-American race were associated to increased risk of developing GERD. Patients diagnosed with any of the examined upper gastrointestinal complications experienced an increased risk of graft-failure (hazard ratio 1.58; 95% confidence interval 1.48-1.69) and death (hazard ratio 1.61; 95% confidence interval 1.46-1.77). CONCLUSIONS: Upper gastrointestinal complications are relatively common after kidney transplantation and are associated with a significantly increased risk of graft loss and death. Further research is needed to elucidate mechanisms underlying the observed adverse prognoses conferred by diagnosis of upper gastrointestinal complications after kidney transplant.

Incidence and risk factors for diarrhea following kidney transplantation and association with graft loss and mortality.

BACKGROUND: Gastrointestinal complications after kidney transplantation are associated with inferior graft outcomes. We examined the incidence, risk factors, and outcomes of posttransplantation diarrhea. STUDY DESIGN: Historic cohort study. SETTING & PARTICIPANTS: We examined first kidney transplant recipients in the United States from 1995 to 2002, with follow-up through December 2002. Recipients of multiple organs were excluded. We limited our study population to Medicare beneficiaries. PREDICTORS: Recipient, donor, and transplant characteristics were ascertained by means of US Renal Data System database inquiry. OUTCOMES: Incidence of diarrhea, graft loss, and death after transplantation. First episodes of diarrhea after transplantation were ascertained by using International Classification of Disease, Ninth Revision, Clinical Modification codes using Medicare billing data. Cause of diarrhea was classified as infectious or not and according to specific cause. Graft loss and death were ascertained from the date of the first diarrhea episode. RESULTS: We enrolled 41,442 patients. Mean follow-up was 758 +/- 399 days. We observed 7,103 diarrhea cases and 8,104 graft losses (4,201 deaths). The 3-year cumulative incidence of diarrhea was 22%, with 18% diagnosed as noninfectious diarrhea with an unspecified cause. Using multivariate Cox proportional hazards analysis, factors associated with increased risk of unspecified noninfectious diarrhea were female sex (hazard ratio [HR], 1.40; 95% confidence interval, 1.33 to 1.48), type 1 diabetes (HR, 1.20; 95% confidence interval, 1.06 to 1.37), and regimens containing tacrolimus and mycophenolate mofetil (HR, 1.37; 95% confidence interval, 1.28 to 1.46). Unspecified noninfectious diarrhea was associated with increased risk of graft failure (HR, 2.13; 95% confidence interval, 1.98 to 2.28) and patient death (HR, 2.04; 95% confidence interval, 1.85 to 2.24). LIMITATIONS: Use of claims data to ascertain patient characteristics and events; inability to make causal inference based on retrospective designs. CONCLUSIONS: Regimens containing tacrolimus and mycophenolate mofetil were associated with increased risk of noninfectious diarrhea. Episodes of noninfectious diarrhea doubled the hazard of graft loss and patient death.

The impact of human leukocyte antigen matching on transplant complications and immunosuppression dosage.

Administrative claims data facilitate ascertainment of outcomes not collected by the transplant registry and provide the opportunity to examine prescribed doses of immunosuppressive medications. Here, we examine the impact of human leukocyte antigen (HLA) matching on traditional outcomes, rejection and survival, and use novel methods to examine immunosuppresion doses and complication rates. The central hypothesis tested in this analysis is that HLA-matched recipients receive lower doses of immunosuppression and have fewer posttransplant complications. We break from tradition by examining HLA matching in both living and deceased donor kidney transplants. As secondary aims, we compare the relative impact of class I and II mismatches and describe outcomes achieved with older donors. Medicare claims linked to the United States Renal Data System database for 23,443 kidney transplants were included in the study. A total of 15,793 transplants were DR mismatched (DRMM), 5,340 manifested no DR mismatches (NODRMM), and 2,310 manifested no ABDR mismatches (NOABDRMM). Patients with NOABDRMM experienced lower adjusted risk of rejection (0.66, 95% confidence interval 0.59-0.74, P < 0.001) and lower hazard of graft loss (0.69, 0.61-0.77, P < 0.001) and death (0.76, 0.63-0.92, P < 0.001) compared with those with DRMM. The hazard of cardiac and diabetic complications was similar between recipients of NOADRMM and DRMM transplants, but the hazard of diarrhea was significantly lower (0.82, 0.73-0.92, P < 0.001) in patients with NOABDRMM. The 6-month dose of mycophenolate mofetil was lower in patients with NOABDRMM. This study validates previous studies that indicated significantly lower risks of rejection, graft loss, and death among patients with 0 HLA-A,B,DR mismatches. Use of administrative claims revealed similar rates of cardiovascular complications. However, HLA-matched deceased donor recipients received lower dosages of mycophenolate mofetil and manifested a lower risk of developing posttransplant diarrhea.

Mycophenolate mofetil dose reductions and discontinuations after gastrointestinal complications are associated with renal transplant graft failure.

BACKGROUND: Mycophenolate mofetil (MMF) use in renal transplantation has steadily increased since 1995 because of its ability to lower the risks of rejection and chronic allograft nephropathy. However, significant gastrointestinal (GI) complications may lead to MMF dose reductions and discontinuations. Little is known of the association between MMF dose reductions and discontinuations following GI complications and graft survival. METHODS: Using the United States Renal Data System, we identified 3,675 adult recipients (age >or=18) with a diagnosed GI complication who were prescribed MMF at the time of first GI diagnosis and had Medicare as their primary insurer. MMF doses were ascertained from Medicare payment records. We estimated risk of graft loss associated with MMF dose adjustments after GI diagnosis: dosage unchanged (reference), reduced <50%, reduced >or=50%, and MMF discontinued. Patients were followed until graft loss, death, last recorded immunosuppression prescription, or 3 years posttransplant. RESULTS: Compared to those with no MMF dose reductions or discontinuations, the risk of graft failure increased with MMF doses reduction >or=50% (HR=2.36, 95% CI 1.23-4.54) and those with MMF discontinuation (2.72, CI 1.60-4.64). CONCLUSION: Renal transplant recipients who underwent MMF dose reduction or withdrawal following GI diagnosis are associated with increased risk of graft failure.

Impact of initiating insulin glargine disposable pen versus vial/syringe on real-world glycemic outcomes and persistence among patients with type 2 diabetes mellitus in a large managed care plan: a claims database analysis.

BACKGROUND: Diabetes accounts for almost 15% of all direct healthcare expenditures. Managed care organizations try to reduce costs and improve patient outcomes. Increasing patient persistence with antidiabetes treatment could help achieve these goals. SUBJECTS AND METHODS: A retrospective study was conducted using the Optum Research Database (Optum, Eden Prairie, MN) to analyze clinical and economic outcomes associated with initiation of insulin glargine via a disposable pen (GLA-P) or vial and syringe (GLA-V) among adult, insulin-naive patients with type 2 diabetes mellitus (T2DM). Propensity-matched patient cohorts were assessed for persistence with insulin therapy, glycated hemoglobin (A1C), hypoglycemic events (based on diagnosis codes), and healthcare costs (total paid amount of adjudicated claims) after follow-up at 1 year. RESULTS: In 1,308 matched patients, persistence was significantly higher (P=0.011) and longer (P=0.001) with GLA-P. Follow-up A1C values were significantly lower (P=0.038), and decreases in A1C from baseline significantly larger (P=0.043), in GLA-P than in GLA-V. Significantly fewer hypoglycemic events (P=0.042) were experienced, and a lower rate of diabetes-related inpatient admissions (P=0.008) was reported in GLA-P than GLA-V. Despite higher study drug costs with GLA-P than GLA-V, all-cause and diabetes-related healthcare costs were similar. CONCLUSIONS: In insulin-naive patients with T2DM, initiation of insulin glargine using the disposable pen rather than the vial and syringe is associated with higher persistence, better A1C control, and lower rates of hypoglycemia. The higher study drug costs associated with pen use do not increase total all-cause or diabetes-related healthcare costs. This may help treatment selection for patients with T2DM in a managed care setting.

Cost-Effectiveness Analysis of Atorvastatin versus Rosuvastatin in Primary and Secondary Cardiovascular Prevention Populations in Brazil and Columbia.

BACKGROUND: Latin America has witnessed a marked increase in cardiovascular (CV) disease, the leading cause of death in many countries. The benefits of lipid-lowering therapy to reduce CV-related events are widely accepted. Clinical evidence suggests that rosuvastatin is associated with slightly greater reductions in low-density lipoprotein cholesterol levels than is atorvastatin at comparable doses. Rosuvastatin, however, is often priced at a premium. OBJECTIVE: Our objective was to examine the cost-effectiveness of using atorvastatin versus rosuvastatin in reducing CV events in Brazil and Colombia using real-world prices. METHODS: A global Markov cohort model of primary and secondary CV prevention was developed and adapted to Brazilian and Colombian settings. The risks and costs of major CV events and efficacy, adherence, and costs of statins were considered. Total gains in life-years, quality-adjusted life-years, major CV events avoided, and costs over the lifetime horizon were estimated. Several dose comparisons were considered. RESULTS: In the Colombian analyses, differences in drug costs between therapies were considerable while outcomes were similar. The incremental cost per quality-adjusted life-year gained for rosuvastatin versus atorvastatin was more than $700,000 and $200,000 in primary and secondary prevention, respectively. Brazilian analyses found lower incremental cost-effectiveness ratios for rosuvastatin at some dose comparisons due to similar pricing between statins. Sensitivity analyses revealed that changes in treatment efficacy and adherence had the largest impact on results. CONCLUSIONS: In primary and secondary CV prevention, the efficacy advantage of rosuvastatin was minimal, while its acquisition cost was higher, particularly in Colombia. The incremental cost-effectiveness ratios were, therefore, generally in favor of atorvastatin being the cost-effective option.

Community-acquired pneumonia episode costs by age and risk in commercially insured US adults aged ≥50 years.

BACKGROUND: Community-acquired pneumonia (CAP) causes substantial clinical and economic burden. While several studies have reported the cost to treat CAP, there is little information on the cost to treat by age, risk profile, and hospitalization in US adults aged ≥50 years. OBJECTIVE: To quantify the cost, from a payer perspective, of treating CAP at the episode level, stratified by age, risk profile, and hospitalization. METHODS: A retrospective study of claims data from a large US health plan (1 January 2006-31 December 2008) was conducted. Patients aged ≥50 years having at least one medical claim with a primary diagnosis for pneumonia were identified. A CAP episode was defined as the period between the first and last pneumonia ICD-9 code with a chest X-ray claim. Episode-level variables included risk stratum based on presence of an immunocompromising/chronic condition, age group, number and length of inpatient and outpatient CAP episodes, and all-cause and CAP-related healthcare costs (adjusted to 2011 costs). RESULTS: Among the 27,659 study patients, 28,575 CAP episodes (20,454 outpatient; 8,121 inpatient) occurred. Mean age of patients with a CAP episode was 62.6. Low-risk patients accounted for 44.4 % of all CAP episodes. Mean CAP episode length was 31.8 days for an inpatient episode and 10.2 days for an outpatient episode. Mean all-cause total healthcare cost for an inpatient CAP episode ranged from $11,148 to $51,219 depending on risk stratum and age group. Mean outpatient episode-related costs were much lower than inpatient episode-related costs. CONCLUSIONS: Cost to treat CAP requiring hospitalization is high regardless of age or the presence of underlying comorbidities. Given that almost half of the patients in this study did not have traditional risk factors for CAP, it is clear that better preventative strategies are needed.

Bleeding as an outcome among patients with nonvalvular atrial fibrillation in a large managed care population.

BACKGROUND: Patients with nonvalvular atrial fibrillation (NVAF) are at increased risk for stroke and bleeding events, but bleeding as an outcome has not been extensively studied in this patient population. OBJECTIVES: The goal of this study was to estimate the incidence of bleeding events among patients with NVAF enrolled in managed care, investigate the relationships between bleeding incidence and bleeding and stroke risks, and estimate health care costs for patients who had a major bleeding event. METHODS: Adults with commercial insurance or Medicare Advantage coverage and health care claims related to AF between January 2005 and June 2009 but with no evidence of valvular disease were included in this retrospective claims data analysis. Baseline stroke risk (CHADS2 [Congestive Heart Failure, Hypertension, Age >75 Years, Diabetes Mellitus, and Prior Stroke or Transient Ischemic Attack]) and bleeding risk (HAS-BLED [Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratios, Elderly, Drugs/Alcohol]) were estimated. Bleeding events were identified during the variable follow-up period, which lasted from the date of the first qualifying AF visit until the earlier of death, disenrollment from the health plan, or June 30, 2010. Bleeding events were classified as major, serious nonmajor, or minor. Health care costs for patients with major bleeding events were calculated. RESULTS: Among 48,260 patients with NVAF (mean age, 67 years), 34% had an incident bleeding event during a mean (SD) follow-up period of 802 (540) days. Incidence rates for bleeding events of any severity and major events were 29.6 and 10.4 per 100 patient-years, respectively. Bleeding incidence rates increased with greater CHADS2 and HAS-BLED risk scores. All-cause health care costs for patients during a major bleeding event averaged $16,830. Average costs per patient with a major event increased from approximately $52 per day in the prebleeding period to approximately $63 per day in the postbleeding period. Costs for patients who did not experience a major bleeding event averaged approximately $38 per day. CONCLUSIONS: Bleeding incidence among patients with NVAF in a real-world setting was high and increased with greater stroke and bleeding risk scores. Health care costs for patients with major bleeding events were elevated. All rights reserved.

Warfarin use and stroke risk among patients with nonvalvular atrial fibrillation in a large managed care population.

BACKGROUND: Stroke prevention is a goal of atrial fibrillation (AF) management, but discontinuation of warfarin anticoagulation therapy is common. OBJECTIVE: To investigate the association between warfarin discontinuation and hospitalization for stroke among nonvalvular AF (NVAF) patients enrolled in managed care. METHODS: Patients with NVAF who initiated warfarin therapy from January 2005 through June 2009 were included. Warfarin discontinuation was defined as a supply gap >60 days without evidence of International Normalized Ratio measurements. Follow-up, which was a variable time period from warfarin initiation until the earlier of death, disenrollment from the health plan, or June 30, 2010, was divided into periods of warfarin treatment and discontinuation. Stroke events were identified based on claims for inpatient stays with a primary diagnosis of stroke or transient ischemic attack. Cox proportional hazards models were constructed to assess the relationship between warfarin discontinuation and incident stroke while adjusting for baseline demographics, stroke and bleeding risk, and comorbidities, as well as time-dependent antiplatelet use, stroke, and bleeding events in the previous warfarin treatment period. RESULTS: Among warfarin initiators with NVAF (N = 16,253), 51.4% discontinued warfarin therapy at least once during a mean follow-up of 668 days. Stroke risk was significantly greater during warfarin discontinuation periods compared with therapy periods (hazard ratio = 1.60; 95% CI, 1.35-1.90; P < 0.001). CONCLUSIONS: More than half of patients on warfarin had treatment gaps or discontinued therapy. Therapy gaps were associated with increased stroke risk.

Predicting long-term graft survival in adult kidney transplant recipients.

The ability to accurately predict a population's long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population's long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS) projections were calculated and compared with the population's actual graft survival. The projection curves were created using a two-part estimation model that (1) fits a Kaplan-Meier survival curve immediately after transplant (Part A) and (2) uses truncated observational data to model a survival function for long-term projection (Part B). Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted survival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%). Excellent predictability (41.3%) can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population's long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.