Real-World Treatment Patterns, Clinical Outcomes, and Symptom Burden in Patients With Psoriatic Arthritis Prescribed Ixekizumab in the United States.

OBJECTIVE: The objective of this study was to describe the real-world characteristics and clinical status of patients with psoriatic arthritis (PsA) currently prescribed ixekizumab. METHODS: Data were drawn from the Adelphi PsA Plus Disease Specific Programme (DSP), a cross-sectional survey conducted in the United States between September 2021 and March 2022. Rheumatologists provided data for their next five consulting patients currently receiving ixekizumab, including demographic and clinical characteristics, disease severity, treatment history, reasons for treatment choice, satisfaction with current treatment, and current and historic symptom burden. Patients voluntarily completed questionnaires, providing perceptional data on symptom burden and satisfaction with current treatment. RESULTS: Overall, 68 rheumatologists provided data on 275 patients with PsA, 90 of whom completed the voluntary questionnaire. Patients had been prescribed ixekizumab for a mean of 11.7 (SD 10.6) months. Clinical characteristics, disease severity, and symptom burden of patients with PsA improved significantly from ixekizumab initiation to the most recent consultation, including symptom burden, tender and swollen joint counts, and body surface area affected by psoriasis (all P < 0.001). Both rheumatologists and patients were satisfied with ixekizumab treatment and reported improvements in pain and fatigue. Improvements were noted after more than three months of ixekizumab treatment duration and regardless of whether the patients had prior exposure to an advanced therapy or were treatment naïve. CONCLUSION: Our results indicate that ixekizumab was efficacious in the treatment of PsA in real-world clinical practice, complementing efficacy data from randomized controlled clinical trials. The results of this study may assist rheumatologists and their patients in making informed treatment choices.

Evaluating the efficacy of biologics with and without methotrexate in the treatment of psoriatic arthritis: a network meta-analysis.

INTRODUCTION: An important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy than biologic monotherapy with respect to efficacy outcomes in these patients. OBJECTIVES: To conduct a network meta-analysis (NMA) comparing biologics by treatment class with and without MTX for treatment of adults with active PsA. METHODS: A systematic literature review (SLR) identified randomised, double-blinded, controlled trials, and a Bayesian NMA compared biologics with and without MTX by treatment class (tumour necrosis factor inhibitors (TNFi), interleukin-23 inhibitors (IL-23i) and IL-17i). Efficacy outcomes included American College of Rheumatology 20%, 50% and 70% (ACR20, ACR50 and ACR70) improvement response. RESULTS: The SLR initially identified 31 studies, of which 17 met feasibility criteria for the NMA by containing the 'without MTX' subgroup. For ACR20 efficacy (the most robust assessment examined), all active treatments were significantly better than placebo. No statistically significant differences were demonstrated between biologic monotherapy (for all classes examined) and biologics in combination with MTX for ACR20/50. IL-17i were comparable to IL-23i, and IL-17i were significantly better than TNFi for ACR20. Although limited by fewer trials, TNFi, IL-23i and IL-17i were not statistically different for ACR50/70. CONCLUSIONS: Concomitant use of MTX and biologics did not improve ACR efficacy outcomes versus biologic monotherapy. MTX does not appear to be necessary as a background therapy when biologics are used for the achievement of ACR20/50 responses in patients with PsA.

Treatment patterns in paediatric and adult patients with SLE: a retrospective claims database study in the USA.

OBJECTIVE: To assess real-world treatment regimens and patterns in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) cohorts, including similarities in treatments, duration of use and adherence. METHODS: This retrospective study utilised data from Merative L.P. MarketScan Research Databases (USA). Index date was the date of first SLE diagnosis (2010-2019). Patients aged <18 years (cSLE) and ≥18 years (aSLE) at index date with confirmed SLE diagnosis and ≥12 months continuous enrolment during pre-index and post-index periods were included. The cohorts were stratified based on the presence (existing) or absence (new) of pre-index SLE. Primary outcomes (post-index period) included treatment regimens (all patients), and adherence (proportion of days covered (PDC)) and discontinuation of therapies initiated within 90 days of diagnosis (new patients). Univariate comparisons between cSLE and aSLE cohorts were performed using Wilcoxon rank-sum and χ2 (or Fisher's exact) tests. RESULTS: cSLE cohort included 1275 patients (mean age=14.1 years) and aSLE cohort included 66 326 patients (mean age=49.7 years). Antimalarials and glucocorticoids were commonly used among new (cSLE=64.4%/62.0%; aSLE=51.8%/49.7%) and existing (cSLE=68.6%/58.9%; aSLE=63.8%/51.3%) patients in both cohorts. Median oral glucocorticoid dose (prednisone equivalent) was higher in cSLE vs aSLE (new=22.1 vs 14.0 mg/day; existing=14.4 vs 12.3 mg/day; p<0.05). Mycophenolate mofetil use was higher in patients with cSLE vs aSLE (new=26.2% vs 5.8%; existing=37.6% vs 11.0%; p<0.0001). Compared with aSLE, more patients used combination therapies in cSLE (p<0.0001). Median PDC was higher in cSLE vs aSLE for antimalarials (0.9 vs 0.8; p<0.0001) and oral glucocorticoids (0.6 vs 0.3; p<0.0001). Treatment discontinuation was lower in cSLE vs aSLE for antimalarials (25.0% vs 33.1%; p<0.0001) and oral glucocorticoids (56.6% vs 71.2%; p<0.0001). CONCLUSIONS: Management of cSLE and aSLE includes the same medication classes; differences include more intensive use of therapy in cSLE, warranting the need for approved safe medications for cSLE.

Changes in musculoskeletal disease activity and patient-reported outcomes in patients with psoriatic arthritis treated with ixekizumab: results from a real-world US cohort.

Introduction: Ixekizumab has demonstrated efficacy in pivotal trials in patients with psoriatic arthritis (PsA), both those naïve to prior biologic therapy and those with prior inadequate response or intolerance to biologics; however, minimal information is currently available on the effectiveness of ixekizumab in routine clinical practice. The objective of this study was to investigate the clinical effectiveness of ixekizumab for the treatment of PsA over 6- and 12-month follow-up periods in a real-world setting. Methods: This retrospective cohort study included patients who initiated treatment with ixekizumab from the OM1 PremiOMTM PsA dataset, a dataset of over 50,000 patients with claims and electronic medical record (EMR) data. Changes in musculoskeletal outcomes, such as tender and swollen joint count and patient-reported pain, as well as physician and patient global assessment, as measured using the Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3) were summarized at 6 and 12 months. The RAPID3, CDAI score, and their individual components were assessed in multivariable regressions adjusting for age, sex, and baseline value. The results were stratified by biologic disease-modifying antirheumatic drug (bDMARD) status (naïve vs. experienced) and monotherapy status (monotherapy vs. combination therapy with conventional synthetic DMARDs). Changes in a 3-item composite score derived from a physician global assessment, patient global assessment, and patient-reported pain score were summarized. Results: Among the 1,812 patients identified receiving ixekizumab, 84% had prior bDMARD treatment and 82% were monotherapy users. All outcomes improved at 6 and 12 months. For RAPID3, the mean (SD) change at 6 and 12 months was -1.2 (5.5) and -1.2 (5.9), respectively. Patients overall, bDMARD experienced, and monotherapy patients achieved statistically significant mean change in CDAI and all components from baseline to 6 and 12 months in adjusted analyses. Patients experienced an improvement in the 3-item composite score at both time points. Conclusion: Treatment with ixekizumab was associated with improvements in musculoskeletal disease activity and PROs as assessed by several outcome measures. Future research should assess ixekizumab's clinical effectiveness in the real world across all PsA domains using PsA-specific endpoints.

Real-world treatment patterns of immunosuppressants in Adults with systemic lupus erythematosus: A claims database analysis in the United States.

OBJECTIVE: To explore initiation, persistence, and adherence to second-line prescribed treatments for SLE, specifically regarding the immunosuppressants azathioprine, methotrexate, and mycophenolate (conventional DMARDs), and belimumab (a biologic). METHODS: Clinical and insurance records were obtained for 801 patients with SLE who initiated treatment with azathioprine, belimumab, methotrexate, or mycophenolate between July 2015 and June 2019. The date of initiation defined the index date, with a 6-month pre-index and 12-month post-index period. Patient characteristics (age, gender, race, sex, ethnicity, geographic region of the US, diagnosing specialty, and type of insurance) and treatment patterns were tabulated overall and by each index medication. Logistic regression was used to model predictors of persistence for the entire sample and for each treatment cohort. FINDINGS: Approximately one-third of patients initiated methotrexate (n = 282, 35.2%) or mycophenolate (n = 258, 32.2%), with the remaining receiving azathioprine (n = 173, 21.6%) or belimumab (n = 88, 11.0%). 30% of patients were persistent with their index immunosuppressant therapy over the 12-month follow-up. The most common non-persistent treatment pattern was discontinuation which occurred in 55% of patients and was highest in the mycophenolate (58%) and lowest in the azathioprine (47%) groups. In total, 17% of patients switched to a different immunosuppressant, which was highest for the belimumab (25%) group. The average time to discontinuation was over 3 months and average time to switch was about 5 months, with patients receiving azathioprine tending to have shorter and belimumab having longer times to discontinuation or switch.Predictors of persistence were limited. Patients under the care of rheumatologists versus primary care and having higher co-morbidity assessed by CCI were associated with non-persistence for the overall sample. Race, number of SLE-related medications, census region, sex, and age were not found to be significantly related to non-persistence of immunosuppressants in this study.

Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications among patients with psoriatic arthritis treated with IL-17A inhibitors in the United States.

BACKGROUND: Much of the current research on treatment patterns and use of adjunctive pain and anti-inflammatory medications among patients living with psoriatic arthritis (PsA) predates the approval and uptake of IL (interleukin)-17A inhibitors. OBJECTIVE: To compare real-world treatment patterns and use of adjunctive pain and antiinflammatory medications between patients with PsA initiating the IL-17A inhibitors, ixekizumab and secukinumab, in a US-managed care population. METHODS: We conducted a retrospective cohort study using the HealthCore Integrated Research Database. Patients with a PsA diagnosis who initiated ixekizumab or secukinumab treatment between December 1, 2017, and November 30, 2019, were identified. Two cohorts were created based on which of the 2 medications was initiated (index date), and patients with prior use of either drug were excluded, as were patients with ankylosing spondylitis. Patients had to be continuously enrolled in the health plan for 6 months prior to (baseline) and 12 months after the index date (post-index). Inverse probability of treatment weighting was used to minimize confounding from baseline demographic and clinical differences between cohorts. Treatment patterns (dosing, persistence, discontinuation, and switching) and use of adjunctive pain/anti-inflammatory medications were assessed and compared between weighted cohorts using chi-square and t-tests. RESULTS: In total, 407 patients were identified in the ixekizumab cohort (mean age 51.6 years; 54% female) and 1,508 patients were identified in the secukinumab cohort (mean age 50.1 years; 59% female). Prior to weighting, presence of a psoriasis diagnosis code (ixekizumab: 60% vs secukinumab: 45%; standardized difference [std diff] = -0.30), specialty of the index prescriber (std diff = 0.38), and mean number of prior advanced therapies (2.0 vs 1.5; std diff = -0.33) were different between cohorts. Cohorts were well balanced after weighting. The majority of secukinumab patients (71%) received an index dose of 300 mg. Rates of persistence (ixekizumab: 40% vs secukinumab: 43%; P = 0.411) and switching (25% vs 20%; P = 0.072) were not statistically different between cohorts. Use of new adjunctive pain and anti-inflammatory medications was not statistically different between cohorts either (ixekizumab: 63% vs secukinumab: 58%; P = 0.187). CONCLUSIONS: Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications were similar in patients with PsA initiating ixekizumab and secukinumab in this US-managed care population. Further research examining reasons for discontinuation, switching, and use of adjunctive medications may help inform treatment decisions for patients living with PsA. DISCLOSURES: Ms Pizzicato, Ms Ketkar, and Dr Grabner are employees of HealthCore, Inc, which received funding from Eli Lilly and Company for the conduct of the study on which this manuscript is based. Ms Pepe was an employee of HealthCore, Inc., during the time the study was conducted. Dr Grabner is a shareholder of Elevance Health (legacy Anthem, Inc.). Dr Vadhariya, Dr Birt, and Ms Bolce are employees of Eli Lilly and Company, the manufacturer of ixekizumab (Taltz). Dr Birt and Ms Bolce are shareholders of Eli Lilly and Company. Dr Walsh is a paid consultant to Eli Lilly and Company and Novartis, the manufacturers of ixekizumab (Taltz) and secukinumab (Cosentyx), respectively. Additionally, Dr Walsh is a paid consultant for Pfizer, Janssen, AbbVie, and UCB and has contracts with Pfizer, AbbVie, and Merck.

Patterns of Lipid Lowering Therapy Use Among Older Adults in a Managed Care Advantage Plan in the United States.

Background: The prevalence of cardiovascular events is increasing. There are many new lipids lowering therapies available in recent years. Increased evidence through literature and guidelines suggests that the use of lipid lowering therapy (LLT) benefits patients who are at risk for cardiovascular events.Objective: The objective of this study was to describe the current LLT use as well as patterns of treatment modification among adults ≥ 65 years.Methods: A retrospective analysis of administrative claims data between January 2016 and May 2018 was conducted. Patients with a LLT refill and continuous enrollment during 1-year prior and 1-year follow-up were identified. The treatment episodes captured were interruption of therapy, intensity changes, dose changes, treatment augmentation, switching, and discontinuation. An analysis of treatment patterns among patients ≥75 years was also performed.Results: The study included 14,360 patients with a LLT of which 99% of patients were on statins as monotherapy or combination. Overall non-statin therapy use either as monotherapy or combination was 2.1%. There were significant differences among new initiators and existing users of therapy. Among prevalent users 57.4% had no changes in the follow-up period, 13.6% interrupted therapy, and 6.6% discontinued. Among new users, 47.9% patients had interrupted therapy, 25% had no changes, and 21.9% discontinued therapy.Conclusion: Most patients were on monotherapy and statins with low non-statin use. The new users among them were more likely to discontinue and interrupt therapy, highlighting the limitations and issues that older patients face that need to increase adherence.

Outcomes of "Real-World" Insulin Strategies in the Management of Hospital Hyperglycemia.

CONTEXT: Guidelines recommend scheduled long-acting basal and short-acting bolus insulin several times daily to manage inpatient hyperglycemia. In the "real world," insulin therapy is complicated, with limited data on the comparative effectiveness of different insulin strategies. OBJECTIVE: This work aimed to evaluate the association of different insulin strategies with glucose control and hospital outcomes after adjustment for patient and physician factors that influence choice of therapy. METHODS: This retrospective, observational study took place at an academic hospital. Participants included noncritically ill hospitalized medical/surgical patients (n = 4558) receiving subcutaneous insulin for 75% or longer during admission. Insulin therapy was grouped into 3 strategies within the first 48 hours: basal bolus (BB: scheduled long and short/rapid n = 2358), sliding scale (SS: short/rapid acting n = 1855), or basal only (BO: long only: n = 345). Main outcome measures included glucose control: hypoglycemic days, hyperglycemic days, euglycemic days, mean glucose; and hospitalization: in-hospital mortality, length of stay (LOS), and readmissions. RESULTS: Initial therapy with BB was associated with more hypoglycemic (2.40; CI, 2.04 to 2.82) (P < .001) and fewer euglycemic days (0.90; CI, 0.85 to 0.97) (P = .003) than SS, whereas BO was associated with fewer hyperglycemic days (0.70; CI, 0.62 to 0.79) (P < .001), lower mean glucose (-18.03; CI, -22.46 to -12.61) (P < .001), and more euglycemic days (1.22; CI, 1.09 to 1.37) (P < .001) compared to SS. No difference in mortality, LOS, and readmissions was found. However, decreased LOS was observed in the BB subgroup with a medical diagnostic related group (0.93; CI, 0.89 to 0.97) (P < .001). CONCLUSION: BO had a more favorable hyperglycemia profile than SS. BB, on the other hand, showed worse glycemic control as compared to SS. In the real-world hospital, BO may be a simpler and more effective insulin strategy.

Evaluating perceptions of social determinants of health and Part D star performance of Medicare Advantage-contracted primary care providers serving a South Texas market.

BACKGROUND: Socioeconomic factors can have a significant impact on a patient's health status and could be responsible for as much as 70%-80% of a patient's overall health. These factors, called the social determinants of health (SDoH), define a patient's day-to-day experiences. While the influence of such factors is well recognized, who ultimately is responsible for addressing SDoH in health care remains unclear. Physicians and other clinicians are suitably placed to assess SDoH factors that can impact clinical decision making. Understanding Medicare Advantage (MA)-contracted primary care provider (PCP) SDoH perceptions has yet to be fully explored. OBJECTIVES: To (a) understand MA-contracted PCP perceptions of SDoH and (b) investigate correlations between PCP perceptions and their CMS Part D star performances, as well as their hospital admissions and emergency room admissions. METHODS: Survey data were collected from MA-contracted PCPs serving a South Texas market during 2019. An 8-item survey consisting of short answer, ranking, and multiple-choice questions was deployed at attendance-mandatory provider meetings from August to October. Analyses were conducted to understand the providers' SDoH perceptions. PCP responses were first summarized as frequencies and percentages. Baseline descriptive characteristics of the providers were compared by Medicare star ratings using chi-square tests (for categorical variables) and t-tests (for continuous variables). Group differences in physician beliefs on how SDoH affects patients' overall health (question 1), as well as provider beliefs regarding how SDoH affects patients' medication adherence practices (question 2), were assessed using chi-square and t-tests. Associations of provider SDoH perceptions with hospital admissions and emergency room admissions were also assessed. A Fischer's chi-square test was used to examine associations between how PCPs answered the question regarding lack of consistent transportation (question 3) and emergency room admissions. The relationships between PCP perceptions of whose job it is to address SDoH (question 7) and hospital admissions were also evaluated. RESULTS: The response rate for returned surveys was 89%. Analysis revealed that the top 3 barriers were financial insecurity (24.87%), low health literacy (18.65%), and social isolation (15.03%). However, about 36% of PCPs felt they should be the primary addressor of SDoH. There was a significant association between years of practice and CMS Part D star ratings (P = 0.005). A significant association between responses in belief towards patients' overall health and CMS Part D star ratings was examined (P = 0.047). There was a statistically significant difference in mean hospital admissions with PCP perception of who should address SDOH (P = 0.03). Emergency room admissions was significantly associated with perceptions regarding lack of consistent transportation (P = 0.04). No differences with star ratings were observed. CONCLUSIONS: Previous literature recognize safety and food insecurity as key SDoH barriers. However, they were not among the top SDoH barriers in our survey. Future research should examine patient perceptions of SDoH in this population to identify ways providers can better serve their patients. DISCLOSURES: Funding for this study was provided by CareAllies, a Cigna business. Statistical analysis was completed in partnership with the University of Houston. Payne, Esse, Qian, Serna, Villarreal, and Becho-Dominguez are employees of CareAllies. Mohan and Abughosh are employed by the University of Houston College of Pharmacy. Abughosh reports grants from Valeant and Regeneron/Sanofi, unrelated to this work. Vadhariya has nothing to disclose. This research was presented virtually at the AMCP Pharmacist Virtual Learning Days event, April 2020, as well as the American College of Clinical Pharmacy Virtual Poster Symposium, May 26-27, 2020.

Impact of a motivational interviewing intervention targeting statins on adherence to concurrent hypertension or diabetes medications.

OBJECTIVE: This study explored if a motivational interviewing intervention customized for statins impacted adherence to concomitantly used antidiabetic/antihypertensive medications. METHODS: The intervention was conducted among patients with a history of suboptimal adherence to statins and included 152 patients in intervention and 304 controls. This retrospective study design identified patients with claims for statins and either antidiabetic/antihypertensive medications. The outcome variable was adherence, measured as proportion of days covered ≥ 0.80, to antidiabetic/antihypertensive medications. Multivariable linear and logistic regression evaluated the effect of intervention on adherence to antidiabetic/antihypertensive medications during the 6 months post-intervention. RESULTS: The antidiabetic group had 53 intervention patients and 102 controls. The antihypertensive group had 80 intervention patients and 159 controls. There was no significant improvement in adherence for antidiabetic/antihypertensive medications following the intervention. Adherence at baseline was a significant predictor of adherence post-intervention in the antidiabetic (OR = 6.5;P < 0.0001) and antihypertensive (OR = 4.1; P = 0.0001 & ß = 0.09; P = 0.008) users. Physician specialty (OR = 3.902; P = 0.01& ß = 0.09; P = 0.015) among antidiabetic users and age >70 years (OR = 2.148; P = 0.025) among antihypertensive users were predictors of adherence. CONCLUSION: The intervention targeting statin did not significantly improve antihypertensive/antidiabetic adherence. PRACTICE IMPLICATIONS: Targeted interventions tailored to patient past adherence and specific medications should be explored.

Patient-reported barriers to statin adherence: Excerpts from a motivational interviewing intervention in older adults.

OBJECTIVE: Despite a known benefit in the reduction of cardiovascular risk, adherence to statins remains suboptimal. A qualitative analysis was conducted within an intervention that identified trajectories of statin adherence in patients and used motivational interviewing (MoI) to improve adherence. The objective of this qualitative study was to evaluate transcripts of an MoI telephonic intervention to identify potential, past, and current barriers to statin adherence and barriers specific to distinct adherence trajectories. METHODS: The MoI intervention was customized by past 1-year adherence trajectories (rapid discontinuation, gradual decline, and gaps in adherence). Two authors independently extracted and documented barriers from phone transcripts. Themes were derived from literature a priori and by cataloging recurring themes from the transcripts. RESULTS: The transcripts of calls made to 157 patients were reviewed of which 25.2% did not communicate a specific adherence barrier despite falling into a low-adherence trajectory when examining refill data. The most commonly reported barriers to statin adherence included adverse effects (40.1%), forgetfulness (30.0%), and lack of skills or knowledge pertaining to statins (25%). More patients in the rapid discontinuation group perceived medication as unnecessary, whereas more patients in the gaps in adherence group reported a communication barrier with their health care provider. Several barriers among patients who fell into low-adherence trajectories were reported. Some patients did not report any barriers, which may have indicated denial. MoI phone calls were useful in providing knowledge, clarifying medication regimens, and reinforcing the need to take statins. CONCLUSION: This study identified patient-reported barriers to statin adherence elicited during an MoI telephonic intervention conducted by student pharmacists. There were differences in barriers reported by patients from each trajectory, which emphasize the need for additional tailored interventions to improve patient adherence.

Evaluating trajectories of statin adherence after a motivational interviewing intervention.

OBJECTIVE: The objective of the current study was to compare postintervention adherence trajectories with preintervention trajectories for those receiving a telephonic motivational interviewing (MoI) intervention to determine predictors associated with each distinct postintervention trajectory and any association between pre- and postintervention trajectories. DESIGN: Retrospective study design using group-based trajectory modeling. SETTINGS AND PARTICIPANTS: A telephonic MoI intervention was conducted by trained student pharmacists to improve statin adherence in a Medicare Advantage plan. Four preintervention adherence trajectories were previously identified: rapid decline (RD), gradual decline (GD), gaps in adherence (GA), and adherent and were used to customize the MoI intervention. Patients from the 3 nonadherent preintervention trajectories were randomized to control or intervention groups and were followed for 6 months from the date of MoI intervention. OUTCOME MEASURES: Group-based trajectory modeling was performed to identify 3 relevant postintervention trajectories. Descriptive statistics were used to assess differences in pre- and postintervention adherence trajectories. Multinomial logistic regression was conducted to determine predictors associated with each identified postintervention trajectory. RESULTS: There were 152 intervention patients and 304 randomly selected controls. The prominent postintervention trajectories that were identified differed from the preintervention trajectories and were (1) GD (17.2%), (2) adherent (61.9%), and (3) discontinuation (20.9%). Among the intervention group, more patients in the GA preintervention trajectory (58.65%) moved to the adherent trajectory postintervention than those in the RD and GD preintervention trajectories. Furthermore, the predictors associated with the postintervention trajectories included MoI intervention, prescriber specialty, presence of diabetes, presence of congestive heart failure, Centers for Medicare & Medicaid Services risk score, and preintervention trajectories. CONCLUSION: The postintervention adherence trajectory patterns differed from the preintervention trajectory patterns with many patients moving into an adherent trajectory especially among those receiving the intervention.

A retrospective study of drug utilization and hospital readmissions among Medicare patients with hepatic encephalopathy.

Hepatic encephalopathy (HE) is a complication occurring in patients with cirrhosis and is associated with neuropsychiatric and motor abnormalities. Symptomatic HE episodes almost always require hospitalization and the frequent recurrence of episodes is associated with poor prognosis and increased medical costs. The utilization of existing therapies for management of HE and adherence to them has yet to be evaluated using real-world claims data.The aim of this study was to evaluate HE drug regimens and adherence and their association with hospital readmissions in Medicare Advantage plan patients.This was a retrospective cohort study of patients discharged from a HE-related hospitalization or emergency room visit. Based on subsequent enrollment in the plan they were categorized into cohorts of 1 month, 3, and 6 months follow-up, and medication regimen was evaluated within the first month. The drugs evaluated included lactulose, rifaximin, and neomycin. Multivariable logistic regression was conducted to evaluate the association of drug regimen and medication adherence measured as proportion of days covered with HE readmissions.There were 347 patients hospitalized for HE with 184 patients having 30-day enrollment and either a drug refill or an outpatient visit in this duration. Medications were not refilled by 67 (36.4%) patients. Various drug regimens had different adherence with mean (standard deviation) proportion of days covered ranging from 0.56 (0.29) to 0.82 (0.16) at 3 months and 0.48 (0.3) to 0.77 (0.15) at 6 months. The results of logistic regression at 3 and 6 months did not show a significant association of medication use or medication adherence with hospital readmissions.Despite availability of therapy, medication utilization was alarmingly low after discharge of patients from HE-related hospitalization. Medication adherence was also low, which may affect the rate of recurrence and costs associated with readmissions. Efforts are needed in both care coordination of these patients to ensure they are prescribed appropriate medications and to enhance adherence to them.

Evaluating Success Factors of a Medication Adherence Tracker Pilot Program in Improving Part D Medication Adherence Metrics in a Medicare Advantage Plan: Importance of Provider Engagement.

BACKGROUND: Health plans and providers can increase quality by improving adherence to chronic disease medications included in star ratings among Medicare Advantage Part D (MAPD) plan enrollees. Research is needed to evaluate effective means of collaboration between health plans and providers. The Medication Adherence Tracker (MAT) is a health plan initiative to help primary care providers use outreach to improve their patients' adherence. OBJECTIVE: To quantify the contribution of structural and process factors on the success of a health plan-initiated tracking system in improving chronic disease medication adherence over 6 months. METHODS: The MAT quality improvement initiative was carried out in South Texas from June to December 2016. Health plan pharmacists used claims data to identify MAPD enrollees at risk of nonadherence to triple-weighted star medications: renin-angiotensin system antagonists, oral diabetes medications, and statins. Actionable reports were delivered biweekly to each provider, either by fax or in person, by embedded health plan nurses. Multivariable regression was used to evaluate sociodemographic and clinical factors as well as the role of provider outreach in increasing paid pharmacy claims and medication adherence as measured by proportion of days covered (PDC) > 0.8. RESULTS: Of 3,542 patients in 5 Texas physician-organized delivery system groups whose 67 providers received tracking reports from June through December 2016, 1,901 (54%) patients had more than 1 related prescription, and 3,064 (87%) received provider outreach on at least 1 prescription. 2,493 (70%) had at least 1 paid pharmacy claim. Provider outreach was associated with greater likelihood of paid prescription claims (relative risk [RR] = 4.59, 95% CI = 3.74-5.62) and greater year-end adherence (PDC > 0.8, RR = 1.86, 95% CI = 1.63-2.12) in multivariable predictive models. 95% CIs for age, gender, low-income subsidy eligibility, and number of prescriptions did not exclude the null value. CONCLUSIONS: Provider engagement is critical to effective health plan-provider partnerships to overcome barriers, change behavior, and improve chronic disease care quality and population outcomes. DISCLOSURES: This study was funded by Cigna. The manuscript was prepared as a work for hire. Hong, Esse, Gallardo, Serna, Fosshat, and Mamvou are employees of CareAllies, a Cigna company. Bruce was employed by Cigna at the time of the study. Vadhariya reports a past internship at Regeneron Pharmaceuticals, unrelated to this work. Abughosh reports grants from Regeneron Pharmaceuticals, Valeant Pharmaceuticals, Sanofi, and BMS/Pfizer, unrelated to this work.

Enhancing Statin Adherence Using a Motivational Interviewing Intervention and Past Adherence Trajectories in Patients with Suboptimal Adherence.

BACKGROUND: Statins have been shown to be effective in reducing the occurrence of cardiovascular (CV) events and are widely prescribed for the risk reduction of CV diseases and recurrent CV events. However, poor adherence prevents some patients from receiving the maximum benefit of the therapy. Motivational interviewing (MoI) is a patient-centered collaborative approach that can be used to improve medication adherence. Group-based trajectory modeling depicts patterns of adherence over time and may help tailor the MoI intervention to further enhance adherence. OBJECTIVE: To assess the effect of a phone-based MoI intervention tailored by patients' past adherence trajectory in improving adherence to statins among patients in a Medicare Advantage prescription drug plan (MAPD). METHODS: Patients continuously enrolled in an MAPD from 2013 to 2017 with a statin prescription between January and June 2015 to allow 2 years of pre-index period and 1 year of follow-up were included in the study. Adherence to statins was measured monthly during the 1-year follow-up as proportion of days covered (PDC) and incorporated into a group-based trajectory model to provide 4 distinct patterns of adherence: adherent, rapid decline, gradual decline, and gaps in adherence. Patients in the 3 nonadherent groups were randomized to either control or intervention. The intervention was an initial counseling call and up to 2 monthly follow-up calls by pharmacy students trained in MoI, providing education consistent with a previously identified pattern of use. Refill data at 6 months post-intervention were evaluated to examine the intervention's effect on PDC, as continuous and dichotomized as PDC ≥ 0.8, as well as discontinuation. Multivariable regression adjusted for baseline demographics, clinical characteristics, and past adherence trajectory. RESULTS: There were 152 patients included in the analysis who received MoI phone calls and 304 randomly selected controls. Mean PDC for the intervention group (0.67 ± 0.3) was significantly higher than the control (0.55 ± 0.4; P < 0.001). The intervention group was also less likely to discontinue (OR = 0.38; 95% CI = 0.19-0.76) and more likely to be adherent in the linear regression model (ß = 12.4; P < 0.001) as well as in the logistic regression model (OR = 1.87; 95% CI = 1.18-2.95). Previous adherence trajectories were significantly associated with adherence in the follow-up. CONCLUSIONS: Patients who received the MoI intervention were more likely to be adherent and less likely to discontinue the statin in the 6 months follow-up compared with controls. Future research can identify other approaches to tailor interventions and expand the intervention to other languages. This intervention may also prove valuable to improve adherence to other medications for chronic and asymptomatic diseases. DISCLOSURES: This study was funded by Regeneron Pharmaceuticals, which provided critical input during study design, implementation, and manuscript preparation. Abughosh reports grants from Sanofi, BMS/Pfizer, and Valeant Pharmaceuticals, unrelated to this study. Vadhariya reports a past internship at Regeneron Pharmaceuticals, unrelated to this study. Esse, Serna, and Gallardo are employees of CareAllies, a Cigna subsidiary. Boklage is an employee of Regeneron Pharmaceuticals. Choi was an employee of Sanofi during this study. Johnson, Essien, Fleming, and Holstad have nothing to disclose. A poster based on this study was presented at AMCP Nexus 2018; October 22-25, 2018; Orlando, FL.

Group-Based Trajectory Models to Identify Sociodemographic and Clinical Predictors of Adherence Patterns to Statin Therapy Among Older Adults.

BACKGROUND: The benefits of statins in the prevention of primary and secondary atherosclerotic cardiovascular (CV) disease events have been well documented. Suboptimal adherence is a persistent problem associated with increased CV events and increased healthcare utilization. Proportion of days covered (PDC) is widely used to measure medication adherence, and provides a single value that does not adequately depict different adherence behavior patterns. Group-based trajectory modeling has been used to identify adherence patterns (or trajectories) over time. The identification of characteristics unique to each pattern can help in the early identification of patients who are likely to be poor adherents and can inform the development of interventions. OBJECTIVES: To identify distinct trajectories of statin adherence in patients enrolled in a Medicare Advantage plan and the sociodemographic and clinical predictors associated with each trajectory. METHODS: Patients were included in the study if they were continuously enrolled in a Medicare Advantage plan between 2013 and 2016 and had a statin prescription between January 2015 and June 2015. We observed each patient for 360 days and computed the monthly PDC. The monthly PDC was incorporated into a group-based trajectory model to provide distinct patterns of adherence. Using group-based trajectory modeling, the patients were categorized into groups based on their adherence patterns. Multinomial logistic regression was performed to identify the sociodemographic and clinical factors associated with each group. RESULTS: A total of 7850 patients were included in the analysis and were categorized into 4 distinct groups based on statin adherence-rapid discontinuation (7.8%), gradual decline (16.8%), gaps in adherence (17.2%), and high or nearly perfect adherence (58.2%). Significant predictors of being placed into one or more of the low-adherence trajectories compared with the high-adherence trajectory included sex, age, low-income subsidy, language, Charlson Comorbidity Index score, statin intensity, and 90-day refills. CONCLUSIONS: The predictors identified in this study provide valuable insight into patient characteristics that increase the risk for statin nonadherence, which has the potential to inform targeted interventions. Identifying patient trajectories can inform the future development of protocols to individualize appropriate interventions for these patients.

The risk of varenicline-induced seizure among those who have attempted to quit smoking using pharmacotherapy.

OBJECTIVE: Varenicline is an effective smoking cessation agent; however, its use is limited because of black box warnings issued by regulatory agencies in the U.S. and Australia. The U.S. Food and Drug Administration updated the label for varenicline in 2015 to warn about the risk of varenicline-induced seizures. The objective of this study was to examine the risk of seizure associated with varenicline use. METHODS: A nested case-control study was performed using IMS LifeLink PharMetrics Plus administrative claims data (2009-2015). The outcome was presumptive seizures. All smokers making an attempt to quit smoking and having no recent seizure events were included in the nest. Cases and controls were matched (1:4) on age (±5 years), sex, index date (±30 days), event date, and duration of enrollment. An exposure period of 90 days preceding the event date was used. Chi-square tests were used to compare the characteristics of cases and controls. Conditional logistic regression was conducted to determine if an association between presumptive seizures and varenicline use exists. RESULTS: Our final sample was comprised of 1342 cases and 5368 controls. The adjusted analysis showed that odds of a seizure for patients with a varenicline prescription were 1.09 (confidence interval [CI] = 0.88-1.36) times those of patients with no varenicline exposure. CONCLUSIONS: This study did not find a significant association between varenicline and increased risk of presumptive seizures. These findings raise questions regarding the necessity for a warning label for increased risk of seizures associated with varenicline.

Direct oral anticoagulants versus aspirin for venous thromboembolism prophylaxis after orthopedic surgery.

PURPOSE: The risks of venous thromboembolism (VTE) and bleeding with direct oral anticoagulants (DOACs) and aspirin for thromboprophylaxis after orthopedic surgery were studied. METHODS: A single center, retrospective study was conducted to examine patients who underwent a major orthopedic surgery from 2011 to 2015. The primary endpoint evaluated was the net clinical outcome of bleeding and thrombosis rates between the DOAC and aspirin groups. Secondary endpoints included bleeding rates, thrombosis rates, transfusion rates, and 90-day readmission rates. The primary endpoint was analyzed using adjusted logistic regression model with propensity score added as an independent variable. RESULTS: A total of 420 patients were included in this study. The proportion of patients with composite primary outcome was similar between the groups (12.9% and 13.3%, in the DOAC and aspirin groups, respectively; p > 0.5). VTE events were numerically lower in the DOAC group, but the result was not statistically significant. Readmission due to VTE or bleeding and bleeding events were also similar between the groups. The DOAC group had a higher proportion of blood transfusions of at least 2 units of blood postoperatively compared with the aspirin group (p = 0.04). CONCLUSION: No difference in net clinical outcome was observed in patients who received a DOAC or aspirin for VTE prophylaxis after major orthopedic surgery.

Clinical Outcomes Associated with Drug-Drug Interactions of Oral Chemotherapeutic Agents: A Comprehensive Evidence-Based Literature Review.

BACKGROUND: Oral chemotherapy use is increasing due to new drug approvals as well as the convenience of the administration of oral drugs. This increased use also raises concern regarding drug-drug interactions (DDIs) with concomitantly administered drugs, resulting in loss of therapeutic effect, decreased tolerability, and/or increased toxicity. OBJECTIVE: The objective of this study was to review existing evidence of the clinical impact of DDIs with oral chemotherapeutic agents. METHODS: A comprehensive search of literature using PubMed was conducted in April 2018 for studies of DDIs associated with oral chemotherapy. Included studies were in English. We included randomized clinical trials, observational studies, and case reports evaluating a DDI between any oral chemotherapy drug and any other drug. Included studies needed to have at least one outcome of clinical relevance potentially attributed to the DDI, for example, effects on survival or toxicity. The quality of the articles was determined using published metrics appropriate for the study design. RESULTS: There were 2626 studies identified in the initial search, of which 35 met all eligibility criteria. These included 15 retrospective cohort studies, 16 case reports or case series and four post hoc analyses of clinical trials. Among these, DDIs contributed to a statistically significant change in a clinical outcome in 12 studies. Eight of these studies evaluated overall survival and progression-free survival and found that the presence of the DDI was associated with reduced survival. CONCLUSION: Our findings suggest that more real-world studies evaluating the association between oral chemotherapy DDIs and clinical outcomes are needed. The adverse clinical outcomes due to DDIs may be a reason for treatment failures and therapy discontinuation.

Association between industry payments and prescribing costly medications: an observational study using open payments and medicare part D data.

BACKGROUND: While many new medications may offer advantages over existing drugs, some newer drugs are reformulations of existing products that provide little innovation or incremental benefit while driving up drug costs. Despite the lack of benefit of these medications, prescribers may be motivated by payments made by the pharmaceutical industry. The objective of the study was to determine the association between payments made to physicians by the pharmaceutical industry and prescriptions for certain selected costly brand name drugs. METHODS: This was a cross-sectional, retrospective study linking the Open Payments Database and Medicare Part D Prescriber Public Use File for 2014, including 667,278 physicians who prescribed one of 6 brand-name drugs with less costly but similarly effective alternatives: lovastatin ER, almotriptan, amlodipine+olmesartan, ibuprofen+famotidine, saxagliptin+metformin and naproxen+esomeprazole. The primary outcome was the odds of a physician prescribing one of the selected drugs, and the primary predictor was the receipt of any payment from the pharmaceutical industry. RESULTS: The odds of prescribing 3 of the 6 drugs were increased among physicians who received industry payment, compared to those without payment: amlodipine+olmesartan, aOR 1.42, (95% CI 1.36-1.49); saxagliptin+metformin, aOR 1.50, (95% CI 1.42-1.59); and naproxen+esomeprazole, aOR 1.45, (95% CI 1.25-1.68). Payment from the manufacturer of the specific drug, compared to not receiving payment from the drug's manufacturer, was associated with increased odds of prescribing 4 of the 6 drugs: amlodipine+olmesartan, aOR 2.40, (95% CI 2.29-2.52), ibuprofen+famotidine, aOR 8.06, (95% CI 5.42-12.00), saxagliptin+metformin, aOR 2.21, (95% CI 2.10-2.34) and naproxen+esomeprazole, aOR 5.96, (95% CI 5.08-7.00). CONCLUSIONS: A physician-industry financial relationship was associated with increased odds of prescribing costly brand-name drugs of uncertain medical benefit. Patients, as healthcare consumers, should demand transparency from their physicians about payment from the pharmaceutical industry to increase shared decision-making. Physician and policy makers need increased awareness and reflection on how industry payment influences their prescribing practices.