Real-World Treatment Patterns Among Patients with Type 2 Diabetes Mellitus Initiating Treatment with Oral Semaglutide.

INTRODUCTION: The treatment landscape for type 2 diabetes mellitus (T2DM) is complex and constantly evolving, and real-world evidence of prescribing patterns is limited. The objectives of this study were to characterize lines of therapy (LOTs), calculate the length of time spent on each LOT, and identify the reasons for the LOT end among patients who initiated oral semaglutide for T2DM. METHODS: This retrospective, claims-based study included commercial and Medicare Advantage adults with T2DM. Data from November 1, 2019, and June 30, 2020, were obtained from Optum Research Database. Patients with ≥ 1 claim for oral semaglutide and continuous health plan enrollment for ≥ 12 months prior to (baseline period) and ≥ 6 months following (follow-up period) the date of the first oral semaglutide claim were included. LOT 1 began on the date of the first oral semaglutide claim. The start date of any subsequent LOTs was the date of the first claim for an additional non-insulin anti-diabetic drug class or a reduction in drug class with use of commitment medications. The LOT ended at the first instance of medication class discontinuation, change in regimen or end of follow-up. RESULTS: Of the 1937 patients who initiated oral semaglutide, 950 (49.0%) remained on their initial regimen over the 6-month follow-up period, 844 (43.6%) had at least one subsequent LOT, and 89 (4.6%) had at least two subsequent LOTs. Among patients with more than one LOT, approximately 20%-25% used oral semaglutide as monotherapy or combination therapy during LOTs 2 and 3. Metformin was frequently used during treatment across all LOTs. CONCLUSION: This study provides insight for physicians and payers into the real-world prescribing practices within the first 6 months following oral semaglutide initiation and fills the gap in understanding the frequency of regimen changes in the constantly evolving and complex environment of T2DM care.

Type 2 diabetes mellitus is a disease which, over time, can cause higher than normal levels of sugar in the blood (hyperglycemia) which can be harmful if not treated. Treatment for type 2 diabetes mellitus can be complex, and how doctors prescribe medications is always changing. For some people with type 2 diabetes mellitus who are overweight or obese, it is recommended for patients to use certain medications that can help with weight management such as semaglutide and metformin. This study aims to fill gaps in current treatment knowledge about type 2 diabetes mellitus patients and their treatment of oral semaglutide. Researchers in this study explored how patients treated with oral semaglutide differentiated among line of therapies, how long patients stuck to them and why they stopped. The study found that those patients who started with oral semaglutide, almost half of those patients stuck to their initial treatment plan for the entire 6 months. When it came to the top ten treatment plans, about 20% of patients used oral semaglutide alone and about 25% of patients used oral semaglutide plus an additional treatment option. Metformin was frequently used during treatment across all line of therapies. There is little information on the real-life setting of treatment after the start of therapy for type 2 diabetes mellitus. The results from this study show what happens when patients start using oral semaglutide and helps healthcare providers understand how often treatment plans can change in type 2 diabetes mellitus care.

Glycemic and Cost Outcomes among Hispanic/Latino People with Type 2 Diabetes in the USA Initiating Dulaglutide versus Basal Insulin: a Real-World Study.

INTRODUCTION: Optimal glycemic management after diabetes onset remains a challenge in Hispanic/Latino adults with type 2 diabetes (T2D), often resulting in poor health outcomes and higher rates of diabetes-related complications. The aim of this study was to examine and compare demographic and clinical characteristics, glycemic outcomes, health care resource utilization (HCRU), and costs among injection-naïve Hispanic/Latino adults with T2D initiating dulaglutide or basal insulin. METHODS: This retrospective, observational study used administrative claims data from the Optum Research Database. Hispanic/Latino adults with T2D were assigned to dulaglutide or basal insulin cohorts on the basis of pharmacy claims and were propensity-score matched on demographic and baseline characteristics. Measures of glycemic management included 12 month follow-up glycated hemoglobin (HbA1c) and change in HbA1c from baseline. Follow-up all-cause and diabetes-related HCRU and costs, including costs per 1% change in HbA1c, were compared between cohorts. RESULTS: The final propensity-score matched sample included 2872 patients: 1436 patients in each cohort. Mean (SD) reduction in HbA1c from baseline to 12 month follow-up was greater in the dulaglutide cohort compared with the basal insulin cohort [-1.40% (1.88) versus -0.92% (2.07); p < 0.001]. The dulaglutide cohort had significantly lower proportions of patients with ≥ 1 all-cause and diabetes-related outpatient visits, emergency room visits, and inpatient stays compared with the basal insulin cohort (p < 0.05). The dulaglutide cohort had significantly lower all-cause total costs per 1% HbA1c reduction than the basal insulin cohort ($13,768 versus $19,128; p < 0.001). Diabetes-related costs per 1% reduction were numerically lower for the dulaglutide cohort, but the difference was not statistically significant ($9737 versus $11,403; p = 0.081). CONCLUSIONS: Dulaglutide demonstrated better glycemic outcomes and lower all-cause costs per 1% HbA1c reduction among Hispanic/Latino adults compared with those initiating basal insulin. Our real-world findings in the Hispanic/Latino population were consistent with results obtained from the overall population and confirm the glycemic benefits of dulaglutide observed in clinical settings.

Treatment patterns of galcanezumab versus standard of care preventive migraine medications over 24 months: a US retrospective claims study.

OBJECTIVE: To describe long-term (24-month) treatment patterns of patients initiating galcanezumab versus standard of care (SOC) preventive migraine treatments including anticonvulsants, beta-blockers, antidepressants, and onabotulinumtoxinA using administrative claims data. METHODS: This retrospective cohort study, which used Optum de-identified Market Clarity data, included adults with migraine with ≥1 claim for galcanezumab or SOC preventive migraine therapy (September 1, 2018 - March 31, 2020) and continuous database enrollment for 12 months before (baseline) and 24 months after (follow-up) the index date (date of first claim). Baseline patient demographics, clinical characteristics, and treatment patterns were analyzed after 24-month follow-up, including adherence (measured as the proportion of days covered [PDC]), persistence, discontinuation (≥60-day gap), restart, and treatment switch. Propensity score matching (1:1) was used to balance the galcanezumab and SOC cohorts. RESULTS: The study included 2307 matched patient pairs with 24-month follow-up. The mean age across cohorts was 44.5 years (females: ∼87%). Patients in the galcanezumab versus SOC cohort demonstrated greater treatment adherence (PDC: 48% vs. 38%), with more patients considered adherent (PDC ≥80%: 26.6% vs. 20.7%) and persistent (322.1 vs. 236.4 d) (all p < .001). After 24-month follow-up, fewer galcanezumab-treated patients had discontinued compared with SOC-treated patients (80.1% vs. 84.7%; p < .001), of which 41.3% and 39.6% switched to a non-index medication, respectively. The most prevalent medication patients switched to in both cohorts was erenumab. Significantly greater proportions of patients who initiated galcanezumab versus SOC medications switched to fremanezumab (p < .001) and onabotulinumtoxinA (p = .016). CONCLUSION: Patients who initiated galcanezumab for migraine prevention had higher treatment adherence and persistence compared with those who initiated SOC medications after 24-month follow-up.

Only few patients (3 − 13%) with migraine, who qualify for preventive treatment, are using them. Conventional preventive treatments have not been developed specifically for migraine treatment, and more than half of the patients stop using them prematurely. Calcitonin gene-related peptide monoclonal antibodies such as galcanezumab, fremanezumab, and erenumab are newer treatments that provide migraine-specific preventive treatment. Prior studies have compared 6- to 12-month migraine medication use by patients starting galcanezumab versus those starting traditional standard of care (SOC) migraine preventive medications. We compared long-term (24-month) migraine medication use in patients starting galcanezumab versus those starting SOC migraine preventive medications to confirm if the results are sustained over a longer period. Over 24 months, patients who used galcanezumab followed the prescribed treatment regimen to a greater extent compared with those who used SOC medications (48% vs. 38%, respectively). Additionally, patients using galcanezumab continued treatment for a longer time compared with those using SOC. Over 24 months, about 85% of patients stopped taking SOC medications, while around 80% of patients stopped taking galcanezumab. Our findings indicate that patients with migraine are more likely to continue using galcanezumab as a preventive treatment for a longer period compared with SOC medications. This study helps identify gaps in the preventive treatment of migraine and provides insights on how they are not being used enough.

Real-world glycated haemoglobin changes among type 2 diabetes mellitus patients treated with a maintenance dose of 7 mg or 14 mg of oral semaglutide.

AIM: To describe the change in glycated haemoglobin (HbA1c) among patients with type 2 diabetes following treatment with a 7 or 14 mg maintenance dose of oral semaglutide. MATERIALS AND METHODS: This retrospective, claims-based study included adult patients with type 2 diabetes with a pre-index HbA1c of ≥7%, initiating treatment with oral semaglutide between 1 November 2019 and 30 June 2020; the patients had continuous health plan enrolment for ≥12 months before (pre-index) and ≥6 months following (post-index) the date of the first oral semaglutide claim (index). Patients were required to have a maintenance dose of 7 or 14 mg. Pre-index demographic and clinical characteristics were captured, as were doses at initiation and prescriber specialty. The change in HbA1c between the latest post-index and pre-index HbA1c measurements was calculated among all patients and among those with ≥90 days of continuous treatment (persistent patients). RESULTS: This study included 520 patients, most of whom had a complex medical history, experienced a range of comorbidities and received an average of 11.5 different classes of medications during the pre-index period. The mean HbA1c reduction during the 6-month post-initiation period was 1.2% (p < .001) for all patients and 1.4% (p < .001) for persistent patients. CONCLUSIONS: In this real-world study, patients with a pre-index HbA1c ≥7% who initiated treatment with oral semaglutide with a 7 or 14 mg maintenance dose had significantly lower HbA1c levels following treatment.

Weight management treatment modalities in patients with overweight or obesity: A retrospective cohort study of administrative claims data.

Background: The purpose of this study was to describe demographic and clinical characteristics among patients who have medical encounters for weight management treatments and to investigate the association of those characteristics with treatment modality. Methods: This was a retrospective database study using medical claims, pharmacy claims, and enrollment information from commercial and Medicare Advantage with Part D members in the Optum Research Database from 01/01/2011-2/29/2020. Adult patients with a claim for a weight management treatment from 01/01/2012-2/28/2019 were categorized into cohorts according to the highest intensity intervention received. To examine the association between patient characteristics and treatment modality received, a multinomial logit model was performed. Results: Cohorts by increasing intensity included lifestyle intervention (LSI, n = 67,679), weight reduction pharmacotherapy (WRRx) with an anti-obesity medication (AOM, n = 6,905), weight reduction procedure (WRP, n = 1,172), and weight reduction surgery (WRS, n = 18,036). Approximately 32.1% and 16.6% of patients who received WRS or WRP had an LSI during the 12-month baseline, and only 0.6% and 0.4% had treatment with long-term AOMs. In a multinomial logit model, patients with type 2 diabetes (not including WRRx cohort), respiratory disorders, cardiovascular risk factors, pain disorders, and mental health conditions had increased odds of treatment with higher intensity intervention versus LSI. Patients who were male, received an intervention more recently (2016-2019), or had a Charlson comorbidity score of 1 (compared to 0) had decreased odds of treatment with higher intensity interventions. Conclusion: In this study, age, sex, body mass index, obesity-related complications, and Charlson comorbidity score appeared to influence the type of weight management treatment modality received. This study improves understanding of weight management treatment utilization and identifies gaps and opportunities to improve obesity care with the appropriate use of different treatment modalities.

Real-World Hemoglobin A1c Changes, Prescribing Provider Types, and Medication Dose Among Patients with Type 2 Diabetes Mellitus Initiating Treatment with Oral Semaglutide.

INTRODUCTION: Given the lack of real-world data on oral semaglutide use outside clinical trials, the purpose of this study was to describe dose, prescriber specialty, and change in hemoglobin A1c (HbA1c) after 6 months of oral semaglutide treatment for patients with type 2 diabetes mellitus (T2DM). METHODS: This was a retrospective study among adult patients with T2DM with ≥ 1 claim for oral semaglutide between November 1, 2019`1-June 30, 2020. Patients had continuous health plan enrollment ≥ 12 months prior to (pre-index) and ≥ 6 months following (post-index) the date of the first oral semaglutide claim (index). Dose at initiation and specialty of the prescribing provider were captured. Change in HbA1c between the last post- and pre-index HbA1c measurement was calculated. Patients were stratified by pre-index HbA1c ≥ 9% (poorly controlled) and HbA1c < 9%. RESULTS: A total of 744 HbA1c < 9% and 268 poorly controlled patients were included in the study. Most patients had an initial oral semaglutide dose of 7 mg (49.3%) or 3 mg (42.9%), prescribed most frequently by a primary care provider (27.8%). Mean HbA1c reduction was 0.8% (p < 0.001). Patients with poorly controlled T2DM had greater HbA1c reductions than patients with HbA1c < 9% (2.0% versus 0.4%, p < 0.001). Patients persistent with oral semaglutide (≥ 90 days continuous treatment) had a mean HbA1c reduction of 0.9% (p < 0.001); persistent patients with poorly controlled T2DM had a mean reduction of 2.5%. CONCLUSIONS: Patients with T2DM in this study experienced significant reductions in HbA1c within 6 months following initiation of oral semaglutide. Patients with a higher starting HbA1c experienced greater HbA1c reductions. The initial dose of oral semaglutide was higher than prescribing instructions indicated for more than half of the study patients.

Glycemic and Economic Outcomes in Elderly Patients with Type 2 Diabetes Initiating Dulaglutide Versus Basal Insulin in a Real-World Setting in the United States: The DISPEL-Advance Study.

INTRODUCTION: Treatments like glucagon-like peptide-1 receptor agonists carry low hypoglycemia risk and are recommended for elderly patients with type 2 diabetes (T2D), while some routine treatments, like insulin, increase hypoglycemia risk. The DISPEL-Advance (Dulaglutide vs Basal InSulin in Injection Naïve Patients with Type 2 Diabetes: Effectiveness in ReaL World) study compared glycemic outcomes, healthcare resource utilization, and costs in elderly patients with T2D who initiated treatment with dulaglutide versus those initiating treatment with basal insulin. METHODS: This observational, retrospective cohort study used data from the Optum Research Database. Medicare Advantage patients (≥ 65 years) with T2D were assigned to dulaglutide or basal insulin cohorts based on pharmacy claims and propensity score matched on demographic and baseline characteristics. Change in HbA1c, 12-months follow-up HbA1c, and follow-up all-cause and diabetes-related healthcare resource utilization and costs were compared. RESULTS: Propensity score matching yielded well-balanced cohorts with 1891 patients each (mean age: dulaglutide, 72.09 years; basal insulin, 72.56 years). The dulaglutide cohort had significantly greater mean HbA1c reduction from baseline to follow-up than basal insulin cohort (- 0.95% vs - 0.69%; p < 0.001). The dulaglutide cohort had significantly lower mean all-cause and diabetes-related medical costs (all-cause: $8306 vs $12,176; diabetes-related: $4681 vs $7582 respectively; p < 0.001) and lower mean all-cause total costs ($18,646 vs $20,972, respectively; p = 0.007) than basal insulin cohort. The dulaglutide cohort had significantly lower all-cause and diabetes-related total costs per 1% change in HbA1c than basal insulin cohort (all-cause: $19,729 vs $30,334; diabetes-related: $12,842 vs $17,288, respectively; p < 0.001). CONCLUSIONS: Elderly patients with T2D initiating dulaglutide had greater HbA1c reduction, lower mean all-cause medical and total costs, lower diabetes-related medical costs, and lower total all-cause and diabetes-related costs per 1% change in HbA1c than patients initiating basal insulin. Future studies assessing medications that do not increase hypoglycemia risk could help inform therapeutic strategies in elderly patients.

Antiretroviral therapy among people with HIV with comorbidities in the United States: a retrospective cohort study.

OBJECTIVES: To describe patterns of antiretroviral medications among people with HIV (PWH) who also have common comorbid conditions in a United States cohort. METHODS: This retrospective cohort study used Optum Research Database claims data from 01/01/2017 through 01/31/2019 to identify adult PWH (≥18 years) based on pharmacy claims for ART during 2018. The index date was defined as the first date of an ART claim. Study inclusion required ≥1 HIV/AIDS diagnosis code during the study period, and continuous health plan enrollment 12 months prior to and at least 30 days after the index date. Descriptive statistics were used to report study results. RESULTS: The study population consisted of 17,694 PWH; mean (SD) age 52.2 (12.8) years; 62.0% were ≥ 50 years old. About 50.6% of the study sample had ≥2 comorbidities at baseline. The most prevalent comorbid conditions were hypertension (33.2%), hyperlipidemia (29.7%), neuropsychiatric conditions (26.9%), and cardiovascular disease (11.5%). Most (93.5%) of PWH received a nucleotide reverse transcriptase inhibitor (NRTI) backbone regimen, including tenofovir alafenamide (41.6%), tenofovir disoproxil fumarate (28.1%), and abacavir (22.0%). The most commonly used anchor agents, 62.6%, were integrase strand transfer inhibitors (INSTIs): dolutegravir (30.4%), elvitegravir (24.2%), and raltegravir (7.3%). The proportion of PWH using specific ARTs did not vary significantly with the presence and type of comorbidities. CONCLUSION: From our analyses, ART prescribing did not appear to vary with the presence of comorbidities and potential medication contraindications. ART regimens may have comparable efficacy profiles; however, selection should be guided by each patient's comorbidities to prevent potential comedication drug toxicities.

Real-world primary nonadherence to antiobesity medications.

BACKGROUND: Primary nonadherence (PNA), when a medication is newly prescribed but not filled, has been identified as a major research gap potentially impacting the optimal treatment of patients with overweight and obesity who are newly prescribed antiobesity medications (AOMs). OBJECTIVES: To assess PNA among patients with newly prescribed AOMs and to examine factors associated with PNA to AOMs. METHODS: This was a retrospective study that used the Optum Integrated Clinical plus Claims database to identify individuals who had at least 1 prescription order for an AOM the US Food and Drug Administration approved for long-term use. Individuals with prescription orders between January 1, 2012, and February 28, 2019, were identified, and patient demographics, clinical characteristics, medication prescribed, baseline health care utilization, and obesity-related complications were described by PNA status. PNA was defined as no pharmacy claim for the AOM within 60 days of the date of the new prescription order as identified in electronic health record data. A multivariable logistic regression model was used to examine factors associated with PNA. RESULTS: The study sample included a total of 1,563 patients. The mean body mass index was 38.4 kg/m2; 10.7% were prescribed liraglutide 3.0 mg, 26.0% were prescribed lorcaserin, 36.3% of patients were prescribed naltrexone-bupropion, 5.4% were prescribed orlistat, and 21.6% were prescribed phentermine-topiramate. Most patients (91.1%) exhibited PNA, with only 8.9% filling their newly prescribed AOM within 60 days. Both the adherent and nonadherent groups were predominately female sex, White, and covered by commercial insurance. The mean age was similar between the 2 groups. Most obesity-related complications were less prevalent in the adherent group, although the Charlson comorbidity index score was similar between the 2 groups. After adjustment for patient demographics and clinical characteristics, there was not a statistically significant association between the specific AOM and PNA (P = 0.299). Patients with depression or living in the Midwest or South regions were at significantly increased risk of PNA. CONCLUSIONS: The rate of PNA to AOMs was very high, suggesting barriers in effective medical management of patients with overweight and obesity. Future research is warranted to understand reasons for PNA to AOMs and how to address these barriers. DISCLOSURES: Dr Kan, Dr Bae, Dr Dunn, and Dr Ahmad are employees of Eli Lilly and Company. Ms Buysman and Dr Gronroos are employees of Optum. Dr Swindle was an employee of Optum at the time the study was conducted and is currently employed at Evidera. Dr Bengtson is employed at Boehringer Ingelheim Pharmaceuticals, Inc. (Boehringer Ingelheim has no connection to this study), and during the conduct of this study was employed at Optum.

Healthcare Resource Utilization, Cost and Clinical Outcomes in Patients Diagnosed with COPD Initiating Tiotropium Bromide/Olodaterol versus Fluticasone Furoate/Umeclidinium/Vilanterol Based on Exacerbation History.

Background: ATS and GOLD guidelines recommend treating low-exacerbation risk COPD patients with dual (LAMA/LABA) agents and reserving triple therapy (TT; LAMA/LABA and inhaled corticosteroids [ICS]) for severe cases with higher-exacerbation risk. However, TT often is prescribed across the COPD spectrum. This study compared COPD exacerbations, pneumonia diagnosis, healthcare resource utilization, and costs for patients initiating tiotropium bromide/olodaterol (TIO/OLO) and a TT, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), stratified by exacerbation history. Methods: COPD patients who initiated TIO/OLO or FF/UMEC/VI between 06/01/2015-11/30/2019 (index date=first pharmacy fill-date with ≥30 consecutive treatment days) were identified from the Optum Research Database. Patients were ≥40 years old and continuously enrolled for 12 months during the baseline period and ≥30 days during follow-up. Patients were stratified into GOLD A/B (0-1 baseline non-hospitalized exacerbation), No exacerbation (subset of GOLD A/B), and GOLD C/D (≥2 non-hospitalized and/or ≥1 hospitalized baseline exacerbation). Baseline characteristics were balanced with propensity score matching (1:1). Adjusted risks of exacerbation, pneumonia diagnosis, and COPD and/or pneumonia-related utilization and costs were evaluated. Results: Adjusted exacerbation risk was similar in GOLD A/B and No exacerbation subgroups, and lower in GOLD C/D for FF/UMEC/VI versus TIO/OLO initiators (hazard ratio: 0.87; 95% CI: 0.78, 0.98, p=0.020). Adjusted pneumonia risk was similar between cohorts across the GOLD subgroups. Adjusted COPD and/or pneumonia-related population annualized pharmacy costs were significantly higher for FF/UMEC/VI versus TIO/OLO initiators across subgroups, p<0.001. Adjusted COPD and/or pneumonia-related population annualized total healthcare costs were significantly higher for FF/UMEC/VI versus TIO/OLO initiators in the GOLD A/B and No exacerbation, subgroups, p<0.001 (cost ratio [95% CI]: 1.25 [1.13, 1.38] and 1.21 [1.09, 1.36], respectively), but similar in the GOLD C/D subgroup. Conclusion: These real-world results support ATS and GOLD recommendations for treating low-exacerbation risk COPD patients with dual bronchodilators and TT for more severe, higher-exacerbation risk COPD patients.

Clinical and economic outcomes in patients with chronic obstructive pulmonary disease initiating maintenance therapy with tiotropium bromide/olodaterol or fluticasone furoate/umeclidinium/vilanterol.

BACKGROUND: Clinical practice guidelines recommend dual long-acting muscarinic antagonists (LAMAs)/long-acting ß2agonists (LABAs) as maintenance therapy in patients with chronic obstructive pulmonary disease (COPD) and dyspnea or exercise intolerance. Escalation to triple therapy (TT) (LAMA/LABA/inhaled corticosteroid) is conditionally recommended for patients with continued exacerbations on dual LAMA/LABA therapy. Despite this guidance, TT use is widespread across COPD severities, which could impact clinical and economic outcomes. OBJECTIVE: To compare COPD exacerbations, pneumonia events, and disease-related and all-cause health care resource utilization and costs (in 2020 US dollars) in patients initiating fixed-dose combinations of either LAMA/LABA (tiotropium/olodaterol [TIO + OLO]) or TT (fluticasone furoate/umeclidinium/vilanterol [FF + UMEC + VI]). METHODS: This retrospective observational study of administrative claims included patients with COPD aged 40 years or older initiating TIO + OLO or FF + UMEC + VI from June 2015 to November 2019. TIO + OLO and FF + UMEC + VI cohorts in the overall and maintenance-naive populations were 1:1 propensity score matched on baseline demographics, comorbidities, COPD medications, health care resource utilization, and costs. Multivariable regression compared clinical and economic outcomes up to 12 months in FF + UMEC + VI vs TIO + OLO postmatched cohorts. RESULTS: After matching, there were 5,658 and 3,025 pairs in the overall and maintenance-naive populations, respectively. In the overall population, the risk of any (moderate or severe) exacerbation was 7% lower in FF + UMEC + VI vs TIO + OLO initiators (adjusted hazard ratio [aHR] = 0.93; 95% CI = 0.86-1.0; P = 0.047). There was no difference in the adjusted risk of any exacerbation in the maintenance-naive population (aHR = 0.99; 95% CI = 0.88-1.10). Pneumonia risk was not statistically different between cohorts in the overall (aHR = 1.12; 95% CI = 0.98-1.27) and maintenance-naive (aHR = 1.13; 95% CI = 0.95-1.36) populations. COPD- and/or pneumonia-related adjusted total annualized costs (95% CI) were significantly greater for FF + UMEC + VI vs TIO + OLO in the overall ($17,633 [16,661-18,604] vs $14,558 [13,709-15,407]; P < 0.001; differences [% of relative increase] = $3,075 [21.1%]) and maintenancenaive ($19,032 [17,466-20,598] vs $15,004 [13,786-16,223]; P < 0.001; $4,028 [26.8%]) populations, with significantly higher pharmacy costs with FF + UMEC + VI (overall: $6,567 [6,503-6,632] vs $4,729 [4,676-4,783]; P < 0.001; $1,838 [38.9%]; maintenance-naive: $6,642 [6,560-6,724] vs $4,750 [4,676-4,825]; P < 0.001; $1,892 [39.8%]). CONCLUSIONS: A lower risk of exacerbation was observed with FF + UMEC + VI vs TIO + OLO in the overall population but not among the maintenance-naive population. Patients with COPD initiating TIO + OLO had lower annualized costs than FF + UMEC + VI initiators in the overall and maintenance-naive populations. Thus, in the maintenance-naive population, initiation with dual LAMA/LABA therapy per practice guidelines can improve real-world economic outcomes. Study registration number: ClinicalTrials.gov (identifier: NCT05127304). DISCLOSURES: The study was funded by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI). To ensure independent interpretation of clinical study results and enable authors to fulfill their role and obligations under the ICMJE criteria, BIPI grants all external authors access to relevant clinical study data. In adherence with the BIPI Policy on Transparency and Publication of Clinical Study Data, scientific and medical researchers can request access to clinical study data after publication of the primary manuscript in a peer-reviewed journal, regulatory activities are complete and other criteria are met. Dr Sethi has received honoraria/fees for consulting/speaking from Astra-Zeneca, BIPI, and GlaxoSmithKline. He has received consulting fees for serving on data safety monitoring boards from Nuvaira and Pulmotect. He has received consulting fees from Apellis and Aerogen. His institution has received research funds for his participation in clinical trials from Regeneron and AstraZeneca. Ms Palli was an employee of BIPI at the time the study was conducted. Drs Clark and Shaikh are employees of BIPI. Ms Buysman and Mr Sargent are employees and Dr Bengtson was an employee of Optum, which was contracted by BIPI to conduct this study. Dr Ferguson reports grants and personal fees from Boehringer Ingelheim during the conduct of the study; grants from Novartis, Altavant, and Knopp; grants and personal fees from AstraZeneca, Verona, Theravance, Teva, and GlaxoSmithKline; and personal fees from Galderma, Orpheris, Dev.Pro, Syneos, and Ionis outside the submitted work. He was a paid consultant for BIPI for this study. The authors received no direct compensation related to the development of the manuscript. BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

Comorbidity and comedication burden among people living with HIV in the United States.

OBJECTIVE: To describe the burden of comorbid conditions and comedications among people living with HIV (PLWH) vs. people living without HIV (PLWoH). METHODS: This was a case-control study conducted among insured patients using administrative claims data. Adult PLWH were identified by antiretroviral therapy (ART) claims or HIV/AIDS diagnosis codes from 1 January 2018 to 31 December 2018 (index date was set by the earliest claim). Continuous enrollment was required for ≥12 months pre-index (baseline) and ≥30 days post-index (follow-up). Patients were required to have ≥1 HIV diagnosis during baseline or follow-up. Those with only HIV prophylaxis were excluded. PLWoH were matched 2:1 to PLWH on demographic characteristics. Study outcomes were compared using z-tests with robust standard errors in an ordinary least squares regression or Rao-Scott tests. RESULTS: The study included 20,256 PLWH and 40,512 matched PLWoH, mean age 52 years. PLWH vs. PLWoH had higher mean (SD) Charlson comorbidity index scores (0.93 [1.59] vs. 0.61 [1.28]; p < .001) and a greater proportion had ≥1 comorbidity (69.1% vs. 54.5%, p < .001). The most prevalent comorbidities included hypertension (33.9% vs. 32.2%; p < .001), hyperlipidemia (29.4% vs. 24.6%; p < .001), chronic kidney disease (13.6% vs. 9.4%, p < .001), depression (13.1% vs. 7.3%, p < .001) and substance abuse (12.8% vs. 7.1%, p < .001). Mean (SD) non-ART prescription fills were higher among PLWH vs. PLWoH (11.9 [10.1] vs. 9.2 [9.4]; p < .001). CONCLUSIONS: Multimorbidity and polypharmacy were more prevalent among PLWH vs. matched PLWoH. Findings support the need to consider comorbidities and comedications when choosing ART and to minimize drug-drug interactions and adverse events to improve patient outcomes.

Trends and Characteristics of Global Initiative for Chronic Obstructive Lung Disease Guidelines-Discordant Prescribing of Triple Therapy Among Patients with COPD.

BACKGROUND: Triple therapy (long-acting muscarinic antagonist [LAMA] plus long-acting beta2-agonist [LABA] plus inhaled corticosteroid [ICS]) is recommended by the Global initiative for chronic Obstructive Lung Disease (GOLD) for moderate-to-severe chronic obstructive pulmonary disease (COPD) with a history of frequent and/or severe exacerbation(s) and dyspnea while using dual bronchodilators. However, many patients receive triple therapy contrary to these recommendations. This study describes factors associated with GOLD-discordant triple therapy initiation. METHODS: This retrospective analysis included patients aged 40 and above, with ≥1 COPD diagnosis, who initiated triple therapy (initiation=index date) during the period January 1, 2014 to December 31, 2018 and had ≥12 months pre-index continuous enrollment (baseline). Triple therapy comprised ≥30 days of overlapping LAMA, LABA, and ICS treatments (open triple therapy), or single-inhaler fluticasone furoate/umeclidinium/vilanterol (closed triple therapy). Cohorts were defined based on the absence of baseline maintenance medication use ("maintenance-naïve"), and/or exacerbations ("exacerbation-discordant"), or "dual-discordant" (discordant on both measures). All triple therapy initiators, overall and for each cohort, were described, and predictors of GOLD-discordant triple therapy initiation were identified. RESULTS: Among 21,711 triple therapy initiators, 34.4% were maintenance-naïve, 61.9% exacerbation-discordant, and 22.2% dual-discordant. Triple therapy initiation appeared to increase during the period 2016 to 2018. In 2018 alone, 31.9% and 58.3% of open triple therapy patients were maintenance-naïve and exacerbation-discordant, respectively, versus 37.6% and 64.4% of closed triple therapy patients. Closed triple therapy initiators had 1.65 times greater risk of dual discordance than open triple therapy initiators. Exacerbation-discordant patients initiating closed triple therapy were 1.61 times more likely to be maintenance-naïve than those initiating open triple therapy. CONCLUSION: A substantial proportion of COPD patients initiating triple therapy do not meet GOLD recommendations regarding exacerbation history and/or prior maintenance therapy. Compared with open triple therapy, closed triple therapy initiators were more likely to be dual discordant.

Adherence and usage patterns of inhaled corticosteroids-long-acting beta-agonists by using inhaler-monitoring technology.

Background: Results of previous research indicate that adherence to prescribed inhaled corticosteroid-long-acting beta2-agonist (ICS-LABA) asthma controller medications is suboptimal, yet actual daily-use patterns are unclear and may be influenced by regimen complexity or dosing frequency. Objective: To investigate real-world use of asthma medications by using inhaler sensors for the ICS-LABA controllers: twice-daily fluticasone propionate (FP) plus salmeterol (SAL) and once-daily fluticasone furoate (FF) plus vilanterol (VI); and albuterol rescue medication. Methods: This longitudinal, two-phase, observational study included adults with asthma-prescribed FP-SAL (phase I) or FF-VI (phase II), and albuterol metered-dose inhalers. The participants completed baseline and follow-up surveys, and used clip-on inhaler sensors to monitor real-time inhaler use over the 6-month study period. Pharmacy claims data for the 6-month follow-up period were used to assess refills of ICS-LABA and albuterol inhalers. Results: Patients who used twice-daily FP-SAL received a sufficient dose (≥2 actuations/day) approximately one third of the time, those on once-daily FF-VI received a sufficient dose (≥1 actuation/day) ∼60% of the time. Patients who used once-daily FF-VI were more likely to take their medication as prescribed versus those who used twice-daily FP-SAL. There were no significant differences in the percentage of albuterol-free days (FP-SAL, 68.06% [n = 241]; FF-VI, 72.67% [n = 127]; p = 0.230). Exploratory outcomes are reported in this article's Online Supplemental Material. Claims-based measures of adherence were higher than sensor-based measures, hence claims data may have overestimated adherence, whereas sensors may have more accurately measured patients' medication use. Conclusion: These data supported the use of inhaler sensors as tools to directly and accurately measure ICS-LABA adherence and rescue medication use, and the adherence benefits of once-daily versus twice-daily ICS-LABA regimens.

Lower Hospitalization and Healthcare Costs With Sacubitril/Valsartan Versus Angiotensin-Converting Enzyme Inhibitor or Angiotensin-Receptor Blocker in a Retrospective Analysis of Patients With Heart Failure.

Background Outcomes data among patients with heart failure (HF) with reduced ejection fraction treated with sacubitril/valsartan ( SAC / VAL ) are largely limited to clinical trial results. We compared hospitalization and healthcare costs among real-world patients with HF with reduced ejection fraction treated with SAC / VAL versus angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker ( ACEI / ARB ). Methods and Results Using retrospective administrative claims data, stable patients with HF with reduced ejection fraction treated with SAC / VAL or ACEI / ARB from October 2015 to June 2016 were identified. Postindex hospitalization and healthcare costs were assessed in propensity-matched cohorts using robust variance estimation. Time to first hospitalization was modeled using unadjusted Kaplan-Meier estimates and multivariable models. Postindex all-cause healthcare costs were modeled using an adjusted multivariable model. Among 279 patients per matched cohort, postindex hospitalization risk was lower for SAC / VAL compared with ACEI / ARB using Kaplan-Meier estimation and unadjusted Cox models. For HF hospitalization, the hazard ratio (95% CI) was 0.56 (0.33-0.94; P=0.030). Adjusted results were similar to unadjusted. Mean ( SD ) monthly healthcare costs were lower for SAC / VAL versus ACEI / ARB for all categories except pharmacy, with hospital costs being particularly disparate between cohorts: for HF hospitalization, $248 ($1588) for SAC / VAL versus $1122 ($7290) for ACEI / ARB . The adjusted risk of incurring increased all-cause postindex costs was lower for SAC / VAL versus ACEI / ARB (cost ratio [95% CI] 0.74 [0.59-0.94]; P=0.013). Conclusions In clinical practice, patients with HF with reduced ejection fraction treated with SAC / VAL were less likely to be hospitalized than matched patients treated with ACEI / ARB . Despite higher pharmacy costs, SAC / VAL -treated patients incurred lower monthly medical and total healthcare costs.

Sacroiliac joint fusion health care cost comparison prior to and following surgery: an administrative claims analysis.

PURPOSE: To assess real-world expenditures on surgical and non-surgical treatment for sacroiliac joint (SIJ) pain by comparing direct health care costs before and after surgery in patients who underwent an SIJ fusion (SIJF) procedure. MATERIALS AND METHODS: This retrospective observational study examined administrative claims data (January 1, 2010 to February 28, 2017) for adult commercial health plan members with a medical claim for SIJF. Identified patients were included if they had continuous enrollment in the health plan for 12 months pre-SIJF (baseline period) and 12 months post-SIJF (follow-up period). The outcomes of interest were low back pain-related health care costs in the first three quarters of the baseline period (pre-surgery period; excludes the quarter immediately preceding surgery) and last three quarters of the follow-up period (post-surgery period; excludes the quarter in which SIJF was performed). RESULTS: Some 302 patients met inclusion criteria: 159 patients had the index SIJF in an inpatient hospital setting, 122 in an outpatient hospital setting, 18 in a surgery center, and three in other settings. Mean and median costs in the pre-surgery period were US$16,803 and US$5,849, respectively, and US$13,297 and US$2,269 in the post-surgery period. Median costs were significantly different in the pre- and post-surgery periods (P<0.001), while mean costs were not. Median health care costs in the pre-surgery and post-surgery periods were lower than the corresponding means due to the highly skewed nature of the cost data. CONCLUSION: This health care claims data analysis shows the potential for lower post-operative health care costs compared to pre-operative costs in patients undergoing SIJF. Median low back pain-related costs in the post-surgery period were approximately US$400 per quarter overall and US$250 per quarter for those undergoing SIJF in the non-inpatient setting. Future studies with larger sample sizes and longer follow-up will improve the precision of the cost data.

Glycaemic impact of treatment intensification in patients with type 2 diabetes uncontrolled with oral antidiabetes drugs or basal insulin.

AIMS: To investigate the impact of treatment intensification (TI) on glycaemic outcomes in patients with type 2 diabetes with glycated haemoglobin A1c (A1C) ≥7% after ≥6 months of treatment with 2 oral antidiabetes drugs (OADs) or basal insulin (BI). MATERIALS AND METHODS: Data were extracted from the Optum administrative claims database from 1 January 2009 to 31 August 2015. Patients with TI ≤6 months after the first A1C ≥7% (index date) were compared with patients with no TI (NTI). TI included addition of OAD, GLP-1 receptor agonist or premixed insulin in OAD and BI cohorts, addition of BI and/or bolus insulin in the OAD cohort and addition of bolus insulin or increasing BI dose in the BI cohort. Change from the index A1C value and hypoglycaemia events was compared at 12 months after TI after adjusting for confounders. RESULTS: A total of 3990/28 123 (14.2%) and 10 425/16 140 (65%) of eligible adults in the OAD and BI cohorts, respectively, underwent TI. These patients showed greater adjusted A1C change vs NTI patients (OAD cohort: -0.59% vs -0.25%; BI cohort: -0.30% vs -0.16%; P < .001 for both comparisons), but with higher hypoglycaemia rates (OAD cohort: odds ratio [OR] 1.68; P < .001; BI cohort: OR: 1.23; P = .004) at follow-up. CONCLUSIONS: Clinical inertia appears to be a significant issue in this population. Although associated with more frequent hypoglycaemia, these results demonstrate that timely TI improves A1C levels, highlighting the need for new and improved agents to effectively manage glycaemia while reducing hypoglycaemia risk.

Real-world comparison of treatment patterns and effectiveness of albiglutide and liraglutide.

AIM: To compare medication adherence, discontinuation and glycemic control in patients receiving albiglutide versus liraglutide. PATIENTS & METHODS: Administrative claims data and glycated hemoglobin (HbA1c) results were analyzed from a sample of adult health plan members with Type 2 diabetes. RESULTS: Patients were matched 1:1 in the albiglutide (n = 2213) and liraglutide (n = 2213) overall cohorts and in 244 patients with HbA1c results from each treatment group. Mean HbA1c change from baseline was -1.0% for both groups. At 6 months, mean ± standard deviation adherence was 0.69 ± 0.29 versus 0.64 ± 0.29 (p < 0.001), and discontinuation was 33.2 versus 37.8% (p = 0.002) with albiglutide versus liraglutide, but these were not statistically or clinically different at 12 months. CONCLUSION: Similar treatment patterns and clinically meaningful reductions in HbA1c were observed for both treatments in this real-world comparison.

The Use of Decomposition Methods in Real-World Treatment Benefits Evaluation for Patients with Type 2 Diabetes Initiating Different Injectable Therapies: Findings from the INITIATOR Study.

BACKGROUND: Determining characteristics of patients likely to benefit from a particular treatment could help physicians set personalized targets. OBJECTIVES: To use decomposition methodology on real-world data to identify the relative contributions of treatment effects and patients' baseline characteristics. METHODS: Decomposition analyses were performed on data from the Initiation of New Injectable Treatment Introduced after Antidiabetic Therapy with Oral-only Regimens (INITIATOR) study, a real-world study of patients with type 2 diabetes started on insulin glargine (GLA) or liraglutide (LIRA). These analyses investigated relative contributions of differences in baseline characteristics and treatment effects to observed differences in 1-year outcomes for reduction in glycated hemoglobin A1c (HbA1c) and treatment persistence. RESULTS: The greater HbA1c reduction seen with GLA compared with LIRA (-1.39% vs. -0.74%) was primarily due to differences in baseline characteristics (HbA1c and endocrinologist as prescribing physician; P < 0.050). Patients with baseline HbA1c of 9.0% or more or evidence of diagnosis codes related to mental illness achieved greater HbA1c reductions with GLA, whereas patients with baseline polypharmacy (6-10 classes) or hypogylcemia achieved greater reductions with LIRA. Decomposition analyses also showed that the higher persistence seen with GLA (65% vs. 49%) was mainly caused by differences in treatment effects (P < 0.001). Patients 65 years and older, those with HbA1c of 9.0% or more, those taking three oral antidiabetes drugs, and those with polypharmacy of more than 10 classes had higher persistence with GLA; patients 18 to 39 years and those with HbA1c of 7.0% to less than 8.0% had higher persistence with LIRA. CONCLUSIONS: Although decomposition does not demonstrate causal relationships, this method could be useful for examining the source of differences in outcomes between treatments in a real-world setting and could help physicians identify patients likely to respond to a particular treatment.

Retrospective Study on the Impact of Adherence in Achieving Glycemic Goals in Type 2 Diabetes Mellitus Patients Receiving Canagliflozin.

INTRODUCTION: Adherence is poor among patients taking antihyperglycemic agents (AHAs) for type 2 diabetes mellitus (T2DM). Inadequate adherence has been linked to decreased glycemic control and increased healthcare costs and hospitalizations. We examined the impact of real-world adherence on glycemic control in T2DM patients treated with canagliflozin. METHODS: This retrospective study used US administrative claims data from commercial and Medicare Advantage healthcare enrollees. Study subjects were adult T2DM patients with baseline HbA1c ≥7.0% and a pharmacy claim for canagliflozin between April 01, 2013 and August 31, 2014. Outcomes included treatment patterns, HbA1c reductions and goal attainment, pharmacy costs, and patient characteristics. Adherence, measured by the proportion of days covered (PDC), was calculated as the number of days of canagliflozin availability divided by the length of the follow-up period. Results were analyzed overall and compared between patients who were highly adherent (HA) (PDC ≥0.8) versus less than highly adherent (LHA) (PDC <0.8). RESULTS: The study population included 2261 patients. At the end of follow-up, patients had an overall mean reduction in HbA1c of 0.97%. Those HA had larger reductions in HbA1c than those LHA (1.17% versus 0.73%, respectively, p < 0.001); 24.6% and 59.4% of patients achieved HbA1c goals of <7.0% and <8.0%, respectively. Highly adherent patients were more likely to achieve goals than those LHA. Less than highly adherent patients increased insulin use by 5.4% in the follow-up period, while HA patients decreased the use of most oral AHAs and had no change in insulin use. CONCLUSIONS: Patients had an HbA1c reduction of 0.97% in the 12 months following the first canagliflozin fill. Highly adherent patients achieved a greater reduction in HbA1c at the end of the follow-up period and were more likely to reach HbA1c goals. Highly adherent patients also had reductions in the use of most oral AHAs, while LHA patients saw a small increase in insulin use.