Abstract Background and Aims C3G is characterised by C3 deposition in the glomeruli, caused by dysregulation of the alternative complement pathway. Contemporary datasets on the clinical burden of patients with C3G in the United States (US) are limited. The aim of this analysis was to describe the demographics and clinical characteristics of patients diagnosed with C3G in the US. Methods This was a retrospective cohort analysis of patients with C3G included in the US HealthVerity database with an EMR and linked pharmacy and medical claims data, who were diagnosed between January 1, 2017 and March 31, 2022 and aged ≥12 years at diagnosis. The index date was the date of the first C3G diagnosis, identified by International Classification of Diseases 10th Revision Clinical Modification (ICD-10-CM) and Systematized Nomenclature of Medicine (SNOMED) diagnosis codes. Included patients had database records for ≥12 months before the index date (the baseline period). Patients aged ≥50 years with monoclonal gammopathy of unknown significance (MGUS) were excluded. Patient demographic and clinical characteristic data for the overall population, and stratified by transplant status, were summarised with descriptive statistics. Results Overall, 2021 patients had ≥1 diagnosis of C3G in the US HealthVerity database during the identification period. Of these, 1060 patients did not meet the criteria for the analysis, including 44 patients (2.2%) who were excluded due to the presence of a diagnostic code for MGUS at ≥50 years of age. The final cohort included 961 patients, of whom 62.4% were female. At the index date, mean (standard deviation [SD]) age was 44.4 (19.6) years (Table 1); 80 patients (8.3%) were aged <18 years, 881 (91.7%) were aged ≥18 years, and 156 (16.2%) were aged ≥65 years. Median (lower quartile [Q1], upper quartile [Q3]) database history was 41.7 (25.9, 66.8) months, and mean (SD) follow-up time from the index date was 22.7 months (16.4). Comorbidities recorded during the baseline period included hypertension (57.4%), type II diabetes (25.1%), and congestive heart failure (12.9%). Among patients who were aged ≥65 years vs <65 years at the index date, the proportion of patients with hypertension (93.6% vs 50.4%), type II diabetes (52.6% vs 19.8%), and congestive heart failure (32.1% vs 9.2%) were numerically higher. Of 461 patients (48.0%) with a known chronic kidney disease stage, 282 (61.2%) had stage 3–5 chronic kidney disease during the baseline period. Baseline estimated glomerular filtration rate (eGFR) data were available for 205 patients (21.3%); overall, median (Q1, Q3) eGFR values were 82.0 (48.0, 107.0) mL/min/1.73 m2, and 56.6% of patients had an eGFR value of <90 mL/min/1.73 m2. Among 78 patients (8.1%) with proteinuria data during the baseline period, median (Q1, Q3) proteinuria levels were 1.4 (0.3, 3.3) g/g, and 44 patients (56.4%) had a proteinuria level ≥1.0 g/g. Extrarenal manifestations including ocular haemorrhage/retinal occlusion, pulmonary haemorrhage, ocular drusen, and acquired partial lipodystrophy were recorded in 1.7%, 0.9%, 0.5%, and 0.1% of patients, respectively. Overall, 19 patients (2.0%) had previously undergone a kidney transplant; the proportion who had hypertension, type II diabetes, or congestive heart failure during the baseline period was 89.5%, 31.6%, and 10.5%, respectively. Baseline eGFR data were available for 4 patients (21.1%) who had previously received a kidney transplant (Table 1). Conclusions This contemporary assessment of patients with C3G, using real-world EMR and administrative claims data from a national US cohort, showed that comorbidities around the time of C3G diagnosis were common. Among patients with available eGFR data, the majority exhibited reduced kidney function during the baseline period.

Abstract Background and Aims C3G is characterised by C3 deposition in the glomeruli, caused by dysregulation of the alternative complement pathway. Currently, there are no approved therapies for C3G. The aim of this analysis was to evaluate treatment patterns in patients with C3G in the United States (US). Methods This was a retrospective cohort study of patients with C3G, with an EMR and linked pharmacy and medical claims data in the US HealthVerity database, who were diagnosed between Jan 1, 2017 and Sep 30, 2021 and aged ≥12 years at diagnosis. Included patients had database records for ≥12 months before (baseline period) and after (follow-up period) the index date (date of first C3G diagnosis, identified by International Classification of Diseases 10th Revision Clinical Modification [ICD-10-CM] and Systematized Nomenclature of Medicine [SNOMED] diagnosis codes). Endpoints included: proportion of patients receiving a treatment, including supportive care (angiotensin-converting enzyme inhibitors [ACEi]/angiotensin II receptor blockers [ARB]), immunosuppressants (IM; including corticosteroids [CS]/glucocorticoids [GC] and mycophenolate mofetil [MMF]), and eculizumab; proportion of patients discontinuing treatment; and duration of treatment. Discontinuing treatment was defined as the absence of a subsequent claim for medication for ≥60 days. Results were assessed using descriptive statistics and analysed by Fisher's exact test, Mann–Whitney U test, or Student's t-test, as appropriate. Results The final cohort included 683 patients. Overall, 346 (50.7%) patients had ≥1 treatment record for C3G during follow-up (median follow-up 24.0 months; median time from index to first treatment 1.1 months). Mean age (standard deviation) of treated and untreated patients was 47.7 (19.4) and 39.6 (18.0) years (P < 0.0001), respectively; 54.3% of treated patients and 72.7% of untreated patients were female (P < 0.0001). Comorbidities reported in treated and untreated patients, respectively, included: hypertension (75.1% and 33.5%; P < 0.0001) and type II diabetes (34.7% and 12.8%; P < 0.0001). Baseline proteinuria data were available for 39 (11.3%) treated patients and 11 (3.3%) untreated patients (P < 0.0001). Median (lower quartile, upper quartile) proteinuria levels were 1.9 (0.7, 3.3) g/g and 0.2 (0.1, 2.3) g/g for the treated and untreated populations, respectively (P = 0.05). Among treated patients (n = 346), most (76.0%) received an ACEi/ARB alone in the first line, 14.2% received IM alone, and 5.8% received concomitant ACEi/ARB and IM (Table 1). A small number of remaining patients received a sodium-glucose cotransporter-2 inhibitor (SGLT2i) ± ACEi/ARB (2.9%), or eculizumab ± IM (1.2%). Less than half of treated patients (43.9%) received second-line therapy, and 17.6%, 6.6%, and 2.0%, respectively, received subsequent lines of treatment. Among treated patients, the most common treatment sequence was ACEi/ARB alone in the first line, without subsequent lines of therapy (42.2%); 30.9% of treated patients received IM (alone or in combination with other treatments) at any time during follow-up. Median duration of treatment in months (95% confidence interval) in any line was 14.9 (9.9, 18.4) for ARB, 8.6 (7.5, 11.1) for ACEi, 7.4 (3.3, 22.6) for SGLT2i, 4.7 (3.0, 6.6) for MMF, and 1.0 (0.9, 3.0) for CS/GC. During follow-up, 225 (65.0%) patients discontinued treatment: 22 (9.8%) and 203 (90.2%) patients restarted and did not restart therapy, respectively. Conclusions These real-world data show that only half of patients with C3G had a record of treatment during follow-up. Compared with the untreated population, patients who received treatment were older, more likely to be male, and more likely to have hypertension or type II diabetes. Among treated patients, the most common treatment sequence was supportive care with an ACEi/ARB alone, and less than one-third received IM at any time during follow-up. Use of the complement inhibitor, eculizumab, was low in this population. A large proportion of patients discontinued treatment during follow-up; given the progressive nature of C3G, these data may highlight the need for novel therapies in the treatment of C3G.

Introduction Atypical hemolytic uremic syndrome (aHUS) is associated with dysregulation of the alternative complement pathway and causes significant morbidity and mortality when undiagnosed or inappropriately treated. C5 inhibitors (C5i) improve thrombotic microangiopathy (TMA) response and renal recovery, but significant morbidity may remain. This study described the clinical characteristics and treatment patterns associated with readmission after index hospitalization using real-world evidence from one of the largest, most diverse cohorts of presumed incident aHUS in the United States (US). Methods This was a retrospective cohort study of 634 incident cases among hospitalized adult patients with presumed aHUS derived from the US Premier Healthcare Database, an electronic healthcare records database that contains ~25% of all US hospitalizations (January 1, 2011-June 30, 2021). aHUS was defined as the presence of an International Classification of Diseases (ICD)-9-CM/ICD-10-CM diagnostic code for TMA (446.6, M31.1, M31.10, M31.19) or HUS (283.11, D59.3) and a treatment code (standard charge, HCPCS, ICD-10-PCS) for a C5i, in the absence of a diagnostic code for secondary causes of TMA/HUS or other C5i indications. The proportion of patients readmitted following the index hospitalization was assessed at 30 days and 365 days following discharge, among other timepoints. The time from index hospitalization discharge to all-cause hospital readmission was defined as the number of days from the discharge date of the index hospitalization to the date of all-cause readmission. Readmission for aHUS was defined as a hospitalization lasting ≥2 days to avoid the inclusion of in-hospital infusion clinic visits for C5i treatment. Demographic and clinical characteristics were analyzed using a t-test, Wilcoxon rank test, Fisher's exact test, or Chi-squared test, as appropriate. Results Overall, 78/634 patients (12.3%) died during index hospitalization. Among the 556 patients who survived until discharge, 23.4% and 39.7% had a readmission within 30 days and 365 days, respectively. During the first 365 days, 20.1% of patients required multiple hospitalizations. The median time to first readmission was 27.5 days (interquartile range [IQR]: 9-102 days). Infection was a common cause of readmission (25.6%). Readmission within either 30 or 365 days was associated with longer median time between index admission and therapeutic plasmapheresis (TPE) (3 vs 2 days, p=0.0002, and 3 vs 2 days, p<0.0001, respectively), longer median time between index admission and C5i (10 vs 8 days, p=0.0441, and 10 vs 8 days, p=0.0005, respectively), and longer median time between index admission and renal replacement therapy (RRT; 4 vs 2 days, p=0.0030, and 3 vs 2 days, p=0.0053, respectively). Only readmission within 365 days was associated with median age (52 vs 46 years of age, p=0.0124) or a history of hypertension (80.5% vs 64.5%, p<0.0001), atrial fibrillation (9.5% vs 4.8%, p=0.0363), or heart failure (21.7% vs 14.6%, p=0.0395) at index hospitalization. Readmission within 30 or 365 days was not associated with sex, race, ethnicity, insurance type, geographical region, hospital size or location (rural vs urban), diabetes, chronic kidney disease, myocardial infarction history, TPE, TPE duration, corticosteroids (CS), CS duration, time to CS, RRT requirement, or TMA remission at discharge. Conclusions aHUS readmission rates remain high, despite treatment with C5i, and infection is a common cause of readmission. Delayed TPE, RRT, and C5i treatment for aHUS during index hospitalization, even if only for 1-2 days, were associated with increased readmission within 30 and 365 days. Future efforts should be made to examine the causal relationship between treatment delays and outcomes.

Background:Benzodiazepines are commonly prescribed for insomnia management but are often associated with negative safety outcomes such as falls and abuse, particularly among older adults.Objective:The purpose of this real-world study was to compare the impact of benzodiazepines, low-dose trazodone, and zolpidem immediate release (IR) on healthcare resource utilization (HCRU), and costs among older adults (age ≥ 65 years) with insomnia in the US.Methods:Using the IBM MarketScan Medicare Supplemental Database, older adults with >1 physician-assigned diagnosis of insomnia and treated with benzodiazepines were matched 1:1 on age, sex, and index-date to individuals treated with trazodone, and separately matched 1:1 on age and sex, to individuals treated with zolpidem immediate release (IR). Between-groups differences were analyzed using general linear models (GLMs) that controlled for multiple confounders.Results:Significant between-groups differences in HCRU and costs were observed such that relative to zolpidem IR and separately relative to low-dose trazodone, benzodiazepines were consistently associated with worsened outcomes.Conclusion:These findings build upon and extend prior knowledge on the negative impact of benzodiazepines and suggest directions for future research.

Background: Cardiovascular (CV) event risk, healthcare resource utilization (HCRU) and costs have not been elucidated among hypertension patients with treated insomnia (H + TI). Materials & methods: Adult patients with H + TI were identified in IBM MarketScan databases. H + TI patients were matched 1:1 on age and sex to controls with hypertension but without sleep disorders. Multivariable models were used to estimate associations between treated insomnia and CV event risk, HCRU and costs. Results: In total, 81,502 H + TI patients (mean age = 62 years, 53% female) were matched. Relative to controls, H + TI patients were 2.4 times as likely to have CV events. H + TI patients incurred higher costs per patient per month (US$2343 vs US$1013). Conclusion: Treated insomnia was associated with higher costs and HRCU in hypertension patients.

Falls are a common cause for morbidity and mortality among patients taking prescription insomnia medication. The objective of this study is to compare the risk of falls, all-cause healthcare resource utilization (HCRU), and costs among patients treated with commonly used, older generation insomnia medications and non-sleep-disordered controls. This retrospective cohort study used the IBM® MarketScan® Commercial and Medicare Supplemental Databases to identify patients aged at least 18 years treated with commonly prescribed medications for insomnia (zolpidem, trazodone, benzodiazepines) between 1 January 2012 and 30 September 2017. The insomnia-treated cohort were age- and sex-matched (1:1) to non-sleep-disordered controls. Odds ratios (ORs) compared risk of falls in each cohort, adjusting for covariates. Costs were adjusted to 2018 dollars, the most recent year for the study data. Relative to matched controls (n = 313,086), the insomnia-treated cohort had a higher rate of falls (3.34% vs. 1.33%), and higher risk of falls [OR = 2.36 (95% confidence interval 2.27–2.44)]. Relative to other index treatments, patients treated with trazodone had the greatest risk of falls. Compared with matched controls, the estimated mean number of inpatient visits, emergency department visits, outpatient visits, and mean length of inpatient stay were all significantly higher among patients treated for insomnia. Such patients incurred greater total costs per patient per month than matched controls ($2100 versus $888; estimated mean ratio, 2.36; 95% CI 2.35–2.38; p < 0.0001). Relative to matched controls, the insomnia-treated cohort showed higher risk of falls with greater HCRU and costs. Each outcome measured was highest among patients treated with trazodone, relative to other index treatments. Findings suggest the need for new treatment options to optimize quality of care for patients with insomnia.

Chlormethine (CL) gel is a skin-directed therapy approved for treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in the USA. MF-CTCL has a chronic clinical course, requiring long-term maintenance therapy with one or more therapies. This analysis describes real-world patterns of maintenance therapy and use of concomitant therapy with CL gel among patients with stage IA/IB MF-CTCL. In a US-based registry, MF-CTCL patients treated with CL gel were enrolled between 3/2015 and 10/2018 across 46 centers and followed for up to 2 years. Patient demographics, clinical characteristics, CL gel treatment patterns, concomitant treatments, clinical response, and adverse events (AEs) were collected from medical records. Descriptive statistics are reported. Of the 206 patients with stage IA/IB MF-CTCL, 58.7

Chlormethine gel (also known as mechlorethamine) is a skin-directed therapy approved for daily treatment of MF-CTCL. Previous reports (including Gilmore 2020) explored alternative treatment schedules and suggested schedule changes may benefit patients. Patterns of initial treatment schedule and subsequent changes for chlormethine gel in a real-world setting among patients with MF-CTCL were investigated in an observational US registry between March 2015 and October 2018. Clinical characteristics and treatment information were collected, with patients followed for up to 2 years after baseline, defined here as chlormethine gel initiation. Schedule of chlormethine gel was assessed at office visits, and descriptive statistics were calculated. In sum, 298 patients initiated chlormethine gel treatment with median age 62 years, male preponderance 61% and 69% with clinical stage IA/IB. Of these patients, 267 (90%) remained on treatment ≥6 months, with overall median treatment duration of 1.86 years. Chlormethine gel was initiated daily in 182 (61%) patients, with 53 (29%) of these patients reducing treatment frequency at least once during follow-up. Among the 116 (39%) patients that started with < daily applications, 24 (21%) reduced the treatment schedule during follow-up, while 52 (45%) adopted more-frequent dosing during their treatment course. Approximately 40% of patients initiated treatment below the recommended daily application; however, almost half of these patients subsequently increased treatment frequency. Overall, by 6 months, 157 of 267 (59%) patients on therapy were applying chlormethine gel daily. These results suggest good tolerability of topical chlormethine gel and wide adoption of flexible treatment schedules for patients.

Aims Medication adherence and persistence are important determinants of treatment success in type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis evaluated the real-world adherence, persistence, and in-class switching among patients with T2DM prescribed dipeptidyl peptidase-4 (DPP4) inhibitors. Methods MEDLINE, EMBASE, Cochrane Library, PsychINFO, and CINAHL were searched for relevant observational studies published in the English language up to 20 December 2019. This was supplemented by manual screening of the references of included papers. Random-effects meta-analysis was performed. Results Thirty-four cohort studies involving 594,138 patients with T2DM prescribed DPP4 inhibitors from ten countries were included. The pooled proportion adherent (proportion of days covered (PDC) or medication possession ratio (MPR) ≥ 0.80) was 56.9% (95% confidence interval [CI] 49.3–64.4) at one year and 44.2% (95% CI 36.4–52.1) at two years. The proportion persistent with treatment decreased from 75.6% (95% CI 71.5–79.5) at six months to 52.8% (95% CI 51.6–59.8) at two years. No significant differences in adherence and persistence were observed between individual DPP4 inhibitors. At one year, just 3.2% (95% CI 3.1–3.3) of patients switched from one DPP4 inhibitor to another. Switching from saxagliptin and alogliptin to others was commonest. Conclusions Adherence to and persistence with DPP4 inhibitors is suboptimal but similar across all medications within the class. While in-class switching is uncommon, saxagliptin and alogliptin are the DPP4 inhibitors most commonly switched. Interventions to improve treatment adherence and persistence among patients with T2DM prescribed DPP4 inhibitors may be warranted.

Medication adherence and persistence are important determinants of treatment success in type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis evaluated the real-world adherence, persistence, and in-class switching among patients with T2DM prescribed dipeptidyl peptidase-4 (DPP4) inhibitors. MEDLINE, EMBASE, Cochrane Library, PsychINFO, and CINAHL were searched for relevant observational studies published in the English language up to 20 December 2019. This was supplemented by manual screening of the references of included papers. Random-effects meta-analysis was performed. Thirty-four cohort studies involving 594,138 patients with T2DM prescribed DPP4 inhibitors from ten countries were included. The pooled proportion adherent (proportion of days covered (PDC) or medication possession ratio (MPR) ≥ 0.80) was 56.9% (95% confidence interval [CI] 49.3–64.4) at one year and 44.2% (95% CI 36.4–52.1) at two years. The proportion persistent with treatment decreased from 75.6% (95% CI 71.5–79.5) at six months to 52.8% (95% CI 51.6–59.8) at two years. No significant differences in adherence and persistence were observed between individual DPP4 inhibitors. At one year, just 3.2% (95% CI 3.1–3.3) of patients switched from one DPP4 inhibitor to another. Switching from saxagliptin and alogliptin to others was commonest. Adherence to and persistence with DPP4 inhibitors is suboptimal but similar across all medications within the class. While in-class switching is uncommon, saxagliptin and alogliptin are the DPP4 inhibitors most commonly switched. Interventions to improve treatment adherence and persistence among patients with T2DM prescribed DPP4 inhibitors may be warranted.

BACKGROUND:Adherence and persistence with diabetes medication play an important role in glycemic control and may differ by medication class. However, there is a lack of research comparing diabetes medications in patients with renal impairment, despite the challenges and higher burden associated with managing this population.OBJECTIVE:To compare adherence and persistence among patients with type 2 diabetes mellitus (T2DM) and nondialysis chronic kidney disease (CKD) treated with dipeptidyl peptidase-4 (DPP-4) inhibitors versus pioglitazone.METHODS:This retrospective cohort study used Truven MarketScan administrative claims databases from 2009 to 2015. One-year adherence for patients with T2DM and nondialysis CKD who initiated therapy with either a DPP-4 inhibitor or pioglitazone was measured by proportion of days covered (PDC) following an initial dispensing, and PDC ≥ 0.80 was coded as adherent. Persistence was calculated as the days between the index date and last day with the index medication on hand, based on the end of the last days supply or the end of follow-up (i.e., 365 days), whichever occurred first. Multivariate logistic regression and Cox proportional hazards models were used to estimate confounder-adjusted differences between the groups for adherence and persistence.RESULTS:The final cohort included 9,019 patients (DPP-4 inhibitors: 7,002; pioglitazone: 2,017). In the adjusted analysis, DPP-4 inhibitor users demonstrated a 1.41 (95% CI = 1.25-1.59) higher odds of being adherent compared with pioglitazone users. Overall adjusted HR for persistence was 0.74 (95% CI = 0.69-0.79), which favored DPP-4 inhibitors compared with pioglitazone. Relative to 2010, persistence with pioglitazone decreased in 2011-2012 and then increased in 2013-2014. In the subgroup analysis, DPP-4 inhibitors first had lower (2010: OR = 0.78, 95% CI = 0.70-0.87; 2011-2012: OR = 0.60, 95% CI = 0.54-0.66) and then similar (2013-2014: OR = 1.03, 95% CI = 0.88-1.19) hazards of nonpersistence compared with pioglitazone.CONCLUSIONS:Among patients with T2DM and nondialysis CKD, the use of DPP-4 inhibitors was associated with better adherence compared with pioglitazone. However, following the approval of generic pioglitazone and associated lower cost sharing after 2012, the magnitude of difference in adherence between the medication classes reduced. Similarly, safety warnings in 2011 and approval of generic products in 2012 may have affected pioglitazone persistence, leading to first higher and then similar hazards for nonpersistence with pioglitazone as compared with DPP-4 inhibitors. These shifts in the results for pioglitazone warrant further investigation and close monitoring of the population initiating this medication.DISCLOSURES:No funding was received for this study. The authors have no conflicts of interest to disclose. An abstract for this study was presented as a podium presentation at the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) 2019 Annual Meeting; May 18-22, 2019; New Orleans, LA.

Background: Selection of schizophrenia or bipolar disorder treatments is complicated by treatment-effect heterogeneity. Objectives: This study assessed how clinicians' beliefs and health system/ insurace policies impact choice of atypical antipsychotic agent in schizophrenia and bipolar disorder. Methods: A cross-sectional survey was conducted of members of the American College of Clinical Pharmacy and College of Psychiatric & Neurologic Pharmacists. Beliefs regarding atypical antipsychotic effectiveness and safety, impact of comorbidity on drug selection, and factors influencing atypical antipsychotic therapy selection were assessed. Results: Twenty-four psychiatric pharmacists and 18 psychiatrists participated. Mean age was 39.6 years, 57.1% were female. Most clinicians (64.3%) believed medication effectiveness and safety equally important, while 26.2% believed safety and 9.4% believed effectiveness more important. The most important medication properties for schizophrenia were reducing positive symptoms (92.7%) and hospitalizations (87.8%) and for bipolar disorder were reducing manic episodes (87.8%), episode relapse (53.7%), and hospitalizations (53.7%). Agranulocytosis (78.1%), arrhythmias (70.7%), and extrapyramidal side effects (68.3%) were most concerning. Restrictions affected antipsychotic choice at 80.5% of sites and were believed to affect medication adherence (55.0%) and outcomes (53.4%). Conclusion: Efficacy and safety were considered equally important when choosing atypical antipsychotics. Formulary restrictions were perceived as impacting treatment choice and outcomes.

Background There is little information on medication use, trends across time, and the impact of guidelines on appropriate use of antidiabetic drugs in participants with type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). Methods A cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) from 2005-2016 was carried out for participants with T2DM with and without CKD. Multivariate survey-weighted regression models were used to evaluate trends in antidiabetic drug use across the time periods and CKD severity. Guideline-discordant use of metformin and glyburide were assessed among those with glomerular filtration rate and serum creatinine-based contraindications. Results Out of 3237 study participants with T2DM, 35.9% had CKD. Comparing 2013-2016 with 2005-2008, use of metformin (non-CKD: 69% vs 83.8%, CKD: 58.6% vs 68.2%) increased, whereas the use of sulfonylureas (non-CKD: 46.3% vs 27.2%, CKD: 54.7% vs 36.6%) and thiazolidinediones (non-CKD: 29.3% vs 3.9%, CKD: 24.6% vs 5.5%) decreased. In combined NHANES cycles and across stages of CKD severity, metformin use decreased (non-CKD, stage 1/2, stage 3, stage 4/5: 78.4%, 69.5%, 54.6%, 4.9%, respectively; P < .01), and insulin use increased (18.5%, 26.8%, 25%, 52.8%, respectively; P < .01) from non-CKD to progressed CKD. Guideline-discordant use of metformin and glyburide was observed in 8.3% and 2.8% of the participants, respectively, in 2013-2016. Conclusions Use of particular antidiabetic medications in patients with CKD changed noticeably over the years, most in accordance with guidelines and regulatory decisions. Gaps in quality of care still exist, which warrants increasing awareness and implementing programs to mitigate inappropriate use.

The objective of the study was to compare adherence and persistence among patients with Type 2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease (CKD) treated with Dipeptidyl Peptidase-4 (DPP-4) inhibitor versus pioglitazone. This retrospective cohort study used Truven MarketScan® administrative claims databases from 2009-2015. One-year adherence for patients with T2DM and non-dialysis CKD who initiated therapy with either a DPP-4 inhibitor or pioglitazone was measured by the Proportion of Days Covered (PDC) following an initial dispensing and PDC ≥ 0.80 was coded as adherent. Persistence was calculated as the number of days between the first dispensing and the beginning of a gap of two times the days supply or the end of the last days supply or 365 days, whichever came first. Multivariate logistic regression and cox-proportional hazard models were used to estimate confounder-adjusted differences between the groups for adherence and persistence, respectively. The final cohort included 9,019 patients (DPP-inhibitor: 7002; pioglitazone: 2017). In the adjusted analysis, DPP-4 inhibitor users demonstrated a 1.41 (95% Confidence Interval (C.I.) 1.25-1.59) higher odds of being adherent compared to pioglitazone users. The adjusted hazard ratio for persistence differed by index year. Relative to 2010, persistence with pioglitazone decreased in 2011/2012 and then increased in 2013/2014. The DPP-4 inhibitors first had lower (2010: 0.78 (95% C.I. 0.70- 0.87), 2011/2012: 0.60 (95% C.I. 0.54- 0.66)), and then similar (2013/2014: 1.03 (95% C.I. 0.88- 1.19)) hazards of non-persistence compared to pioglitazone. Among patients with T2DM and non-dialysis CKD, the use of DPP-4 inhibitors was associated with better adherence compared to pioglitazone. Safety warnings in 2011 and approval of generic products in 2012 may have impacted pioglitazone persistence. This inconsistent results for persistence with pioglitazone warrant further investigation.

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF- KDOQI) published guidelines on antidiabetic medication selection and dose adjustments in patients with chronic kidney disease (CKD) which includes avoiding glyburide in moderate to severe CKD and metformin in severe CKD. Analyzing trends in these medication usages can be helpful for determining the need for intervention to address prescribing practices. The objective of this study was to assess antidiabetic medication use in patients with type 2 Diabetes Mellitus (T2DM) and CKD across years and according to CKD stages. We analyzed cross-sectional data from National Health and Nutrition Examination Survey (NHANES) from the years 2005-2012. T2DM was defined by these criteria: self-reported non-gestational diabetes, age over 30 years at time of diagnosis, and lack of insulin use within one year of diagnosis. NKF- KDOQI guidelines were used to define CKD stages. Weighted proportions of patients with different classes of antidiabetic medication use were compared across the years and CKD stages using PROC SURVEY procedures in SAS 9.4. There were total 2046 respondents (2005-06: 366, 2007-08: 548, 2009-10: 586, 2011-12: 546) with T2DM and 37.5% of them had CKD. Overall sulfonylurea and glyburide use in CKD was 43.8% and 16.4% respectively and it did not change substantially over the years. The use of insulin (11.7%-34.4%) and DPP-4 inhibitors (0.0%-11.0%) increased from 2005 to 2012; whereas, thiazolidinedione use decreased (21.1%-7.5%). Metformin use decreased from stage 1(57.9%) to stage 5 (0.0%) of CKD; whereas insulin use increased (13.8% to 63.4%). A substantial number of patients were receiving glyburide which is not recommended in this population. This warrants a need to implement programs designed to reduce inappropriate sulfonylurea use in patients with CKD, where use of these medications can increase risk of hypoglycemia and related complications.

Patients with HER2-positive metastatic breast cancer (MBC) who receive Trastuzumab and/or taxanes often need treatment with different agents, such as Ado-trastuzumab emtansine (TDM-1) or a combination of Lapatinib and Capecitabine (L+C), when disease progresses. Although TDM-1 has better efficacy in improving survival, its high cost compared to L+C needs further economic evaluation. This study aimed to assess the cost-effectiveness of TDM-1 compared to L+C in MBC patients from a U.S. payer’s perspective. A Markov model depicting MBC progression for a total of 120 21-day treatment cycles (6.9 years) was developed. Clinical endpoints in the model included progression-free survival and overall survival. The model included the impact of disease progression and toxicity from cancer drugs. Cancer drug toxicities included were thrombocytopenia, neutropenia, hepatotoxicity, peripheral neuropathy, and pulmonary toxicity. Effectiveness inputs were derived from a Phase-III clinical trial comparing TDM-1 and L+C; cost and utility inputs from published literature and expert opinion. All cost inputs were expressed in 2014 U.S. dollars. The incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life years (QALY) as the effectiveness measure. One-way sensitivity analyses were performed. Patients receiving TDM-1 cost $241,109 with 1.88 QALYs gained over the 6.9 years, compared with $200,541 and 1.56 QALYs in L+C group. The base-case ICER was $124,247/QALY. Compared to L+C, patients treated with TDM-1 had an expected 0.45 years longer survival and 0.31 years longer progression-free survival. The ICER varied from $70,270 to $178,223 per QALY when the TDM-1 cost changed from 80 to 120% of its current price. The determination of TDM-1 being cost-effective for MBC patients depends on the willingness-to-pay threshold used. Patients derived significant life expectancy gains from TDM-1, leading to longer treatment with this costly agent.