Treatment Patterns and Outcomes Before and After Humulin R U-500 Initiation Among US Patients with Type 2 Diabetes Previously Prescribed ≤ 200 Units/day of U-100 Insulin.

INTRODUCTION: Humulin R U-500 (U-500R) utilization has increased in the past few years, raising concerns as U-500R is indicated only for patients requiring > 200 units of insulin. Thus, evidence of dispensed total daily dose (dTDD) > 200 units of prior U-100 insulin based on pharmacy claims is increasingly used as a criterion to determine appropriate switching to U-500R by payers. The study compared the treatment patterns and outcomes before and after U-500R initiation among patients who were identified with ≤ 200 units/day U-100 insulin fill in order to understand the appropriateness of switching. METHODS: Patients with type 2 diabetes who initiated U-500R (index date = first fill) with ≤ 200 units/day pre-index dTDD and > 200 units/day post-index dTDD were identified in a Veterans Health Administration dataset between 1 January 2014 and 30 June 2017. Descriptive analysis was conducted on treatment patterns (dTDD, insulin dosage [units/kg], adherence, number of prescription fills) and clinical outcomes (HbA1c, symptomatic hypoglycemic events). Associations between U-500R exposure and outcomes were evaluated using mixed-effects models. Subgroups of U-500R syringe and KwikPen users were analyzed separately. RESULTS: Among 1191 U-500R initiators identified in the study the mean dTDD increased from the pre- to post-index periods (147.2 vs 346.3; p < 0.0001). The mean HbA1c decreased from pre- to post-initiation (9.6% vs 8.6%; p < 0.0001), and symptomatic hypoglycemia events per patient per year increased (2.0 vs 3.3, p < 0.0001). Mixed-effects models confirmed the significance of the changes (p < 0.0001). Device subgroups followed similar trends. CONCLUSIONS: U-500R initiation was associated with large dTDD increases, improved glycemic control, and modest increases in hypoglycemia events, suggesting U-500R initiation may have corrected previous treatment compliance issues. Imposing dTDDs > 200 units before switching to U-500R criterion could hurt the opportunities for patients who need a simplified regimen for better outcomes.

Treatment patterns and outcomes before and after human regular U-500 insulin initiation via KwikPen® among US veterans with type 2 diabetes mellitus.

INTRODUCTION: A dedicated Humulin R U-500 (U-500R) prefilled disposable insulin pen (KwikPen) became available in 2016, yet limited evidence exists on treatment patterns and outcomes of U-500R via KwikPen (U500-KP). METHODS: This is a retrospective observational study among adults with ≥2 claims for type 2 diabetes initiating U500-KP (index date: first claim) identified in Veterans Health Administration database. Treatment patterns and outcomes were evaluated in 9-month pre- and post-index periods, including dispensed total daily insulin dosage derived from claims expressed in units (dTDD) and units/kg, HbA1c, symptomatic hypoglycemia, and body weight. Multivariable modeling was used to confirm the associations between U500-KP initiation and outcomes. RESULTS: A total of 647 U500-KP initiators were identified. The mean age was 64 years, and mean Quan-Charlson Comorbidity-index score was 3.8. Before U500-KP initiation, 62% of patients had dTDD ≤ 200 units with mean A1c 9.5%. Mean dTDD increased from 188.2 to 269.9 units after U500-KP initiation with mean A1c decreased by 0.83% (SD = 1.67) and mean weight gain of 1.5 kg (SD = 6.74). Hypoglycemia events increased from 4.3 to 5.3 (p < 0.05) per person per year. CONCLUSIONS: Initiation of U500-KP brought significant improvement in dispensed insulin dose and glycemic control accompanied by moderate increases in hypoglycemia and weight.

Treatment Patterns and Outcomes, Before and After Humulin R U-500 Initiation, Among High-Dose Type 2 Diabetes Mellitus Patients in the United States.

OBJECTIVE: Severely insulin-resistant type 2 diabetes (T2D) patients face unique treatment challenges. Humulin R U-500 (U-500R) as insulin monotherapy with both basal/bolus properties addresses these challenges, although it remains understudied. This retrospective study compared real-world patient characteristics, treatment patterns, and outcomes before and after U-500R initiation. METHODS: Adults with T2D on dispensed doses of >180 units/d U-500R monotherapy (index date=first fill) with ≥9-month continuous enrollment both pre- and post-index date and ≥180 units/d insulin pre-index were identified using Veterans Health Administration data (January 1, 2014-January 30, 2017). Overall group was further stratified into elderly and 201 to 300 units dispensed total daily dose (dTDD) subgroups. Syringe and KwikPen users were separately analyzed as subcohorts. Treatment patterns (dTDD), insulin dosage (units/kg), proportion of days covered (PDC) with insulins, and outcomes (HbA1c and hypoglycemic events) were descriptively evaluated, with regression models used to confirm associations between exposure and outcomes. RESULTS: Among 951 U-500R initiators (overall group), mean dTDD (248.5 vs 392.1), percentage of patients with insulin dosage >2 units/kg (38.6% vs 88.1%), and mean PDC (73% vs 77%) significantly increased from the pre- to post-index periods (all P<.001). Changes in HbA1c (9.3% vs 8.5%; P<.0001) and hypoglycemia events per patient per year (2.1 vs 3.1, P<.0001) were statistically significant and confirmed by regression models (P<.0001). Subgroups (elderly, 492; 201 to 300 units, 148) and device subcohorts (syringe, 714; KwikPen, 244) showed similar trends. CONCLUSION: U-500R initiation was associated with significantly improved treatment compliance patterns and glycemic control, with modest increase in hypoglycemia events.

Time to Next Treatment, Health Care Resource Utilization, and Costs Associated with Ibrutinib Use Among U.S. Veterans with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Real-World Retrospective Analysis.

BACKGROUND: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common adult leukemia, accounting for ≈ 37% of all leukemias in the United States. Limited real-word evidence is available on the outcomes of ibrutinib use among previously untreated patients in the U.S. Veterans Health Administration (VHA) population diagnosed with CLL/SLL. OBJECTIVES: To (a) evaluate time to next treatment (TTNT) among U.S. veterans with CLL/SLL who initiated ibrutinib versus chemoimmunotherapy (CIT) in first line (1L) and 1L ibrutinib versus ibrutinib in later lines (2L+) and (b) compare health care resource utilization (HRU) and costs between the 1L ibrutinib and CIT cohorts. METHODS: Adults with CLL/SLL and claims for 1L single-agent ibrutinib or CIT (index date = first prescription claim date) were included from Veterans Health Administration Data (April 1, 2013-March 31, 2018). A subset of the CIT 1L cohort with evidence of ibrutinib in 2L/3L was defined as the ibrutinib 2L+ cohort. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate TTNT, and generalized linear models were used to determine all-cause per patient per month (PPPM) HRU and costs during 1L among propensity score-matched (PSM) cohorts. RESULTS: After PSM, 614 patients were included in each of the 1L ibrutinib and 1L CIT cohorts, and 149 were included in each of the 1L ibrutinib and 2L+ ibrutinib cohorts. The 1L ibrutinib cohort had significantly longer TTNT compared with each of the 1L CIT and 2L+ ibrutinib cohorts (P <0.0001 and P =0.0001, respectively) and was less likely to have a next line of treatment than the CIT 1L cohort (HR = 0.52; 95% CI = 0.42-0.65; P < 0.0001) and the 2L+ ibrutinib cohort (HR = 0.39; 95% CI = 0.22-0.69; P = 0.0012). The 1L ibrutinib cohort had significantly fewer inpatient visits (rate ratio [RR] = 0.38; 95% CI = 0.28-0.52; P ≤ 0.05) and outpatient visits PPPM (RR =0.72; 95% CI = 0.68-0.77; P ≤ 0.5) compared with the CIT 1L cohort. Additionally, the 1L ibrutinib cohort had $7,308 significantly lower monthly medical costs (95% CI = -$9,892 to -$4,895; P ≤ 0.05) versus the 1L CIT cohort, resulting in comparable monthly total health care cost (medical and pharmacy) between real-world 1L patients treated by ibrutinib and CIT (-$2,160; 95% CI = -$4,840-$347; P > 0.05). CONCLUSIONS: These findings demonstrate that among U.S. veterans with CLL/SLL, 1L ibrutinib use was associated with significantly longer TTNT versus that of 1L CIT. Similarly, early treatment with ibrutinib was associated with longer TTNT as compared to ibrutinib use in later lines of therapy. Moreover, 1L ibrutinib was associated with lower HRU and medical costs compared with 1L CIT, completely offsetting the higher pharmacy costs related to 1L ibrutinib treatment. DISCLOSURES: This research was sponsored by Janssen Scientific Affairs. The analyses were performed by STATinMED Research. Huang is an employee of Janssen Scientific Affairs and may own company stock. Sundaram was an employee of Janssen Scientific Affairs at the time this study was conducted. Borra and Janjan are employees of STATinMED Research, a paid consultant to the study sponsor. Wang, Li, and Shrestha were employees of STATinMED Research at the time this study was conducted.

A Lifestyle Intervention via Email in Minority Breast Cancer Survivors: Randomized Parallel-Group Feasibility Study.

BACKGROUND: Our data have indicated that minority breast cancer survivors are receptive to participating in lifestyle interventions delivered via email or the Web, yet few Web-based studies exist in this population. OBJECTIVE: The aim of this study was to examine the feasibility and preliminary results of an email-delivered diet and activity intervention program, "A Lifestyle Intervention Via Email (ALIVE)," delivered to a sample of racial and ethnic minority breast cancer survivors. METHODS: Survivors (mean age: 52 years, 83% [59/71] African American) were recruited and randomized to receive either the ALIVE program's 3-month physical activity track or its 3-month dietary track. The fully automated system provided tools for self-monitoring and goal setting, tailored content, and automated phone calls. Descriptive statistics and mixed-effects models were computed to examine the outcomes of the study. RESULTS: Upon completion, 44 of 71 survivors completed the study. Our "intention-to-treat" analysis revealed that participants in the physical activity track made greater improvements in moderate to vigorous activity than those in the dietary track (+97 vs. +49 min/week, P<.001). Similarly, reductions in total sedentary time among those in the physical activity track (-304 vs. -59 min/week, P<.001) was nearly 5 times greater than that for participants in the dietary track. Our completers case analysis indicated that participants in the dietary track made improvements in the intake of fiber (+4.4 g/day), fruits and vegetables (+1.0 cup equivalents/day), and reductions in saturated fat (-2.3 g/day) and trans fat (-0.3 g/day) (all P<.05). However, these improvements in dietary intake were not significantly different from the changes observed by participants in the physical activity track (all P>.05). Process evaluation data indicated that most survivors would recommend ALIVE to other cancer survivors (97%), were satisfied with ALIVE (82%), and felt that ALIVE was effective (73%). However, survivors expressed concerns about the functionality of the interactive emails. CONCLUSIONS: ALIVE appears to be feasible for racial and ethnic minority cancer survivors and showed promising results for larger implementation. Although survivors favored the educational content, a mobile phone app and interactive emails that work on multiple email domains may help to boost adherence rates and to improve satisfaction with the Web-based platform. TRIAL REGISTRATION: ClinicalTrials.gov NCT02722850; https://clinicaltrials.gov/ct2/show/NCT02722850 (Archived by WebCite at http://www.webcitation.org/6tHN9VsPh).

Pathways between physical activity and quality of life in African-American breast cancer survivors.

INTRODUCTION: Several studies have indicated that the relationship between physical activity and quality of life is not directed but mediated through various pathways. The purpose of this study was to assess the role of cancer-related fatigue, disability, and functional status as potential mediators in African-American breast cancer survivors. METHODS: African-American breast cancer survivors (N = 135, mean age = 63) aged 55 years and older participated in a web-based survey consisting of measures assessing physical activity, functional status, cancer-related fatigue, disability, quality of life, and sociodemographic and medical characteristics. Structural equation modeling was used to assess the structural relationships among the constructs. RESULTS: The initial structural model fit the data and revealed a significant relationship between physical activity and quality of life (ß = 0.34, P < 0.01). Subsequent structural models with proposed complementary and mediating paths of fatigue, function, and disability fit the data. The adjusted model indicated that physical activity was no longer associated with quality of life (ß = 0.11, P > 0.05) and mediated through pathways of functional status and fatigue (total ß = 0.16, P < 0.01). The final adjusted model accounted for 32 % of the variance in quality of life. CONCLUSION: Our data suggest that physical activity may be indirectly related to quality of life through pathways consisting of fatigue and functional status. Further longitudinal studies are needed to test the pathways through which varying levels of physical activity influence cancer-related and quality of life outcomes in minority cancer survivors.

Construct Validity of the Late-Life Function and Disability Instrument in African American Breast Cancer Survivors.

Limited data exist on the validity of the Late-Life Function and Disability (LLFD) instrument in cancer survivors. We examined the construct validity of the abbreviated LLFD instrument in a sample of African-American breast cancer survivors. African American breast cancer survivors (n = 181) aged 50 years and older completed the abbreviated LLFD instrument and questions about sociodemographic and lifestyle characteristics. Confirmatory factor analysis (CFA), Cronbach alphas, and structural models were used to evaluate the construct validity of these measures. Minor modifications were made to the three-factor functional component portion of the inventory to improve model fit. Cronbach alpha's (range 0.85-0.92) and inter-factor correlations (r = 0.3-0.5, all p < 0.05) were appropriate. The two-factor disability component fit the data and Cronbach alpha's (0.91 and 0.98) were appropriate with a high inter-factor correlation (r = 0.95, p < 0.01). The average variance extracted (range = 0.55-0.93) and composite reliabilities (range = 0.86-0.98) were in acceptable ranges. Floor effects ranged from 7% for advanced lower function to 74% for personal role disability. Education and number of comorbidities were correlated significantly with functional outcomes. The abbreviated LLFD instrument had adequate construct validity in this sample of African American breast cancer survivors. Further studies are needed that examine the stability of the instrument over time.