Estimation of adherence to urate-lowering therapy in people living with gout using Australia's Pharmaceutical Benefits Scheme and patient-reported dosing.

AIMS: The aim of this study was to estimate adherence to urate-lowering therapy (ULT), predominately allopurinol, from Australia's Pharmaceutical Benefits Scheme (PBS) claims database in association with (1) patient-reported doses and (2) World Health Organization's (WHO) defined daily doses (DDD), namely, allopurinol (400 mg/day) or febuxostat (80 mg/day). METHODS: Proportion of days covered (PDC) was calculated in 108 Gout App (Gout APP) trial participants with at least two recorded ULT dispensings in an approximately 12-month period before provision of intervention or control apps. Adherence was defined as PDC ≥80%. We measured the correlation between the two methods of calculating PDC using a Wilcoxon signed rank test. Agreement between ULT-taking status (self-reports) and ULT-dispensed status (PBS records) was tested with Cohen's kappa (κ), and positive and negative percent agreement. RESULTS: Allopurinol was prescribed in 93.5% of participants taking ULT. Their self-reported mean daily dose (SD) was 291 (167) mg/day. Mean PDC (SD) for allopurinol was 83% (21%) calculated using self-reported dose, and 63% (24%) using WHO's DDD. Sixty-three percent of allopurinol users were identified as adherent (PDC ≥80%) using self-reported dose. There was good agreement between self-reported ULT use and PBS dispensing claims (κ = 0.708, P < .001; positive percent agreement = 90%, negative percent agreement = 82%). CONCLUSIONS: Participant-reported allopurinol daily doses, in addition to PBS dispensing claims, may enhance confidence in estimating PDC and adherence compared to using DDD. This approach improves adherence estimations from pharmaceutical claims datasets for medications where daily doses vary between individuals or where there is a wide therapeutic dose range.

Medication adherence and costs of medical care among patients with Parkinson's disease: an observational study using electronic medical records.

BACKGROUND: Adherence to antiparkinsonian drugs (APDs) is critical for patients with Parkinson's disease (PD), for which medication is the main therapeutic strategy. Previous studies have focused on specific disorders in a single system when assessing clinical factors affecting adherence to PD treatment, and no international comparative data are available on the medical costs for Chinese patients with PD. The present study aimed to evaluate medication adherence and its associated factors among Chinese patients with PD using a systematic approach and to explore the impact of adequate medication adherence on direct medical costs. METHODS: A retrospective analysis was conducted using the electronic medical records of patients with PD from a medical center in China. Patients with a minimum of two APD prescriptions from January 1, 2016 to August 15, 2018 were included. Medication possession ratio (MPR) and proportion of days covered were used to measure APD adherence. Multiple linear regression analysis was used to identify factors affecting APD adherence. Gamma regression analysis was used to explore the impact of APD adherence on direct medical costs. RESULTS: In total, 1,712 patients were included in the study, and the mean MPR was 0.68 (± 0.25). Increased number of APDs and all medications, and higher daily levodopa-equivalent doses resulted in higher MPR (mean difference [MD] = 0.04 [0.03-0.05]; MD = 0.02 [0.01-0.03]; MD = 0.03 [0.01-0.04], respectively); combined digestive system diseases, epilepsy, or older age resulted in lower MPR (MD = -0.06 [-0.09 to -0.03]; MD = -0.07 [-0.14 to -0.01]; MD = -0.02 [-0.03 to -0.01], respectively). Higher APD adherence resulted in higher direct medical costs, including APD and other outpatient costs. For a 0.3 increase in MPR, the two costs increased by $34.42 ($25.43-$43.41) and $14.63 ($4.86-$24.39) per year, respectively. CONCLUSIONS: APD adherence rate among Chinese patients with PD was moderate and related primarily to age, comorbidities, and healthcare costs. The factors should be considered when prescribing APDs.

The effects of revised peer-counselor support on the PMTCT cascade of care: results from a cluster-randomized trial in Kenya (the EMMA study).

BACKGROUND: This study evaluated the effect of revisions to existing peer-counselor services, called Mentor Mothers (MM), at maternal and child health clinics on medication adherence for women living with HIV (WLWH) in Kenya and on early infant HIV testing. METHODS: The Enhanced Mentor Mother Program study was a 12-site, two-arm cluster-randomized trial enrolling pregnant WLWH from March 2017 to June 2018 (with data collection through September 2020). Six clinics were randomized to continued MM-supported standard care (SC). Six clinics were randomized to the intervention arm (INT = SC plus revised MM services to include more one-on-one interactions). Primary outcomes for mothers were defined as: (PO1) the proportion of days covered (PDC) with antiretroviral therapy (ART) ≥ 0.90 during the last 24-weeks of pregnancy; and (PO2) ≥ 0.90 PDC during the first 24-weeks postpartum. Secondary outcomes were infant HIV testing according to national guidelines (at 6, 24, and 48 weeks). Crude and adjusted risk differences between study arms are reported. RESULTS: We enrolled 363 pregnant WLHV. After excluding known transfers and subjects with incomplete data extraction, data were analyzed for 309 WLWH (151 SC, 158 INT). A small share achieved high PDC during the prenatal and postnatal periods (0.33 SC/0.24 INT achieved PO1; 0.30 SC/0.31 INT achieved PO2; crude or adjusted risk differences were not statistically significant). In addition, ~ 75% in both study arms completed viral load testing during year two after enrollment, with > 90% suppressed in both arms. For infants, ≥ 90% in both arms had at least one HIV test through study follow up (76 weeks) but testing on schedule according to PMTCT guidelines was uncommon. CONCLUSIONS: While national guidelines in Kenya recommended that all HIV-infected pregnant women take a daily antiretroviral regimen for life following a HIV diagnosis, results presented here indicate that a minor share achieved high medication coverage during the prenatal and postnatal periods analyzed. In addition, adjustments to Mentor-Mother services showed no improvement in study outcomes. The lack of effect for this behavioral intervention is relatively consistent with the existing literature to improve mother-infant outcomes along the PMTCT care cascade. CLINICAL TRIAL NUMBER: NCT02848235. Date of first trial registration 28/07/2016.

Association between statin adherence and the risk of stroke among South Korean adults with hyperlipidemia.

BACKGROUND AND AIMS: The effectiveness of statins commonly used to prevent stroke may depend on adherence to treatment. We examined the association between statin adherence and stroke risk among South Korean adults with hyperlipidemia. METHODS AND RESULTS: The data of 128,052 and 129,390 participants with hyperlipidemia for the purpose of studying the risks of ischemic and hemorrhagic stroke, respectively, were collected from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2013. Participants were divided into groups according to statin adherence, calculated as the proportion of days covered (PDC; poor, moderate, good). The risk of ischemic and hemorrhagic stroke were analyzed using a Cox proportional hazards model. Individuals with poor PDC exhibited higher risks of ischemic and hemorrhagic stroke than those with good PDC (ischemic stroke: hazard ratio [HR] = 1.09, 95% confidence interval [CI] = 1.03-1.15, hemorrhagic stroke: HR = 1.37, 95% CI = 1.22-1.54). Women with poor PDC were at higher risk of ischemic stroke than those with good PDC (HR = 1.17, 95% CI = 1.09-1.26), while men with poor PDC exhibited a higher risk of hemorrhagic stroke than those with good PDC (HR = 1.55, 95% CI = 1.27-1.90). Individuals with disabilities who had poor PDC were at higher risk of ischemic stroke than those with good PDC (HR = 1.55, 95% CI = 1.24-1.93). CONCLUSIONS: We detected a significant association between statin adherence and ischemic and hemorrhagic stroke risk. Therefore, hyperlipidemia patients should adhere to statin treatment; such interventions are required to reduce the stroke risk.

The Impact of Patient Access to Their Electronic Health Record on Medication Management Safety: A Narrative Review.

Introduction: As the American's Federal Health Insurance Portability and Accountability Act (HIPAA) stated that patients should be allowed to review their medical records, and as information technology is ever more widely used by healthcare professionals and patients, providing patients with online access to their own medical records through a patient portal is becoming increasingly popular. Previous research has been done regarding the impact on the quality and safety of patients' care, rather than explicitly on medication safety, when providing those patients with access to their electronic health records (EHRs). Aim: This narrative review aims to summarise the results from previous studies on the impact on medication management safety concepts of adult patients accessing information contained in their own EHRs. Result: A total of 24 studies were included in this review. The most two commonly studied measures of safety in medication management were: (a) medication adherence and (b) patient-reported experience. Other measures, such as: discrepancies, medication errors, appropriateness and Adverse Drug Events (ADEs) were the least studied. Conclusion: The results suggest that providing patients with access to their EHRs can improve medication management safety. Patients pointed out improvements to the safety of their medications and perceived stronger medication control. The data from these studies lay the foundation for future research.

High level of medication adherence is required to lower mortality in patients with chronic hepatitis B taking entecavir: A nationwide cohort study.

It is unclear whether suboptimal adherence contributes to adverse clinical outcomes in patients with chronic hepatitis B (CHB). Moreover, there is no consensus regarding the optimal level of drug adherence. This was a population-based historical cohort study including 51 975 adult CHB patients treated with entecavir (0.5 mg/d orally). Data were obtained from the Korean national health insurance service claims database, which covers >99% of the entire population, between 2007 and 2015. Medication adherence was categorized as high (proportion of days covered [PDC], ≥90%; n = 32 089), intermediate (PDC, 80%-89%; n = 10 197) and low (PDC, <80%; n = 9689). During a median 4.5 years (maximal 9 years) of follow-up in 51 975 CHB patients treated with entecavir, multivariable analyses revealed that the risk of mortality/transplantation was significantly greater in the low-adherers (adjusted hazard ratio [HR], 1.38; P < .001) and intermediate-adherers (adjusted HR, 1.44; P < .001) than the high-adherers (P for trend < 0.001). The risk of renal failure in the low- and intermediate-adherence groups was also significantly higher than the high-adherence group (P for trend < 0.001). By contrast, the risk of hepatocellular carcinoma (HCC) was not significantly different between groups (P for trend = 0.70). The higher risk of mortality/transplantation and renal failure but similar risk of HCC for low- and intermediate-adherers compared with high-adherers was consistent in inverse probability treatment weighting analysis of the entire cohort and subcohorts with or without cirrhosis. In conclusion, high medication adherence (≥90%) is required to significantly lower risk of mortality and renal failure in patients with CHB during long-term treatment with entecavir.

Trends in coagulation factor replacement therapy and medical costs in patients with haemophilia in Taiwan: A population-based, 15-year analysis.

INTRODUCTION: Taiwan's National Health Insurance Program approved reimbursement of prophylactic coagulation factor replacement therapy (CFRT) for patients with haemophilia (PWH) in 2014. AIM: To examine 15-year trends and the impact of reimbursement for prophylactic CFRT on its utilization and related medical costs for PWH. METHODS: We analysed Taiwan's National Health Insurance Database from 2003 to 2017. We included patients with haemophilia A (PWHA) or B (PWHB) receiving coagulating factor. Female patients were excluded because of small sample size. We analysed annual consumption of CFRT units and medical costs. High proportion of days covered (PDC) with CFRT served as an indicator for prophylactic treatment since it reflects routine use of CFRT. We applied interrupted time series analysis (ITSA) to evaluate the impact of reimbursement for prophylactic CFRT on usage patterns and medical costs. RESULTS: We included 896 male PWHA and 181 male PWHB, with 38.1% and 37.0% aged under 18 years, respectively. By ITSA, we found the trends in coagulation factor consumption and PDC significantly increased after reimbursement for prophylactic CFRT in both PWHA and PWHB (p values for trend change <0.05). The overall medical costs per patient increased with increasing consumption of coagulation factor; however, ITSA revealed non-CFRT cost decreased after reimbursement of prophylactic CFRT for both PWHA and PWHB (p values <.05). CONCLUSION: Reimbursement for prophylactic CFRT facilitated growth in rates of prophylactic CFRT and increased related costs, but curbed rising non-CFRT costs. These findings provide strong grounds for future cost-effectiveness studies to leverage prophylactic CFRT for its therapeutic benefits.

Medication adherence to rivaroxaban and dabigatran in patients with non-valvular atrial fibrillation: a meta-analysis.

Several real-world studies have evaluated adherence to direct acting oral anticoagulants in patients with non-valvular atrial fibrillation (NVAF); however, these studies have not been systematically summarized. We performed a meta-analysis to compare adherence to rivaroxaban versus dabigatran therapy in United States (US) patients with NVAF in a real-world setting. Medline and Scopus were searched from January 2010 to August 2018 using keywords and MeSH terms related to adherence and oral anticoagulants. We included real-world studies of US adults with NVAF comparing adherence to dabigatran and rivaroxaban. Studies evaluating adherence by a measure other than proportion of days covered (PDC) were excluded. The proportion of patients with a PDC ≥ 80 (a commonly utilized definition of adherence) served as the primary outcome of interest. We conducted meta-analysis of non-overlapping studies using the Hartung-Knapp random-effects model to estimate risk ratios (RRs) with corresponding 95% confidence intervals (CIs). We included 5 studies evaluating 80,230 patients (range 2667-22,571). Median follow-up across studies was 6 months (range 3-12 months). The proportion of patients with a PDC ≥ 80 ranged from 59.5 to 83.5% for rivaroxaban users and 57.3 to 78.3% for dabigatran users. Upon meta-analysis, rivaroxaban use was associated with increased adherence compared with dabigatran use (RR 1.08; 95% CI 1.03-1.12; I2 = 88%). In conclusion, rivaroxaban was associated with increased adherence when compared to dabigatran in ~ 80,000 patients in a real-world setting. Possible explanations for this include dosing frequency or patient tolerance.

Methods for Measuring Multiple Medication Adherence: A Systematic Review-Report of the ISPOR Medication Adherence and Persistence Special Interest Group.

BACKGROUND: A broad literature base exists for measuring medication adherence to monotherapeutic regimens, but publications are less extensive for measuring adherence to multiple medications. OBJECTIVES: To identify and characterize the multiple medication adherence (MMA) methods used in the literature. METHODS: A literature search was conducted using PubMed, PsycINFO, the International Pharmaceutical Abstracts, the Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library databases on methods used to measure MMA published between January 1973 and May 2015. A two-step screening process was used; all abstracts were screened by pairs of researchers independently, followed by a full-text review identifying the method for calculating MMA. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to conduct this systematic review. For studies that met the eligibility criteria, general study and adherence-specific characteristics and the number and type of MMA measurement methods were summarized. RESULTS: The 147 studies that were included originated from 32 countries, in 13 disease states. Of these studies, 26 used proportion of days covered, 23 used medication possession ratio, and 72 used self-reported questionnaires (e.g., the Morisky Scale) to assess MMA. About 50% of the studies included more than one method for measuring MMA, and different variations of medication possession ratio and proportion of days covered were used for measuring MMA. CONCLUSIONS: There appears to be no standardized method to measure MMA. With an increasing prevalence of polypharmacy, more efforts should be directed toward constructing robust measures suitable to evaluate adherence to complex regimens. Future research to understand the validity and reliability of MMA measures and their effects on objective clinical outcomes is also needed.

Multifaceted interventions improve medication adherence and reduce acute hospitalization rates in medicaid patients prescribed asthma controllers.

OBJECTIVE: To measure the effectiveness of managed care-led interventions in Medicaid subjects with asthma on medication adherence and acute hospitalization in Pennsylvania. METHODS: A total of 3589 members (age range, 5-64 years) served by two Pennsylvania-based Medicaid managed care plans (southeastern Pennsylvania [SEPA] and Lehigh-Capital/New West Pennsylvania [LCNWPA]) with low adherence rates (proportion of days covered [PDC]; 20%-67%) for asthma controller prescription fills in 2012 were guided through a care continuum by a comprehensive asthma strategy, consisting of adherence-improvement interventions (grouped as general intervention [GI] or personalized intervention [PI] for higher-risk subjects). Medication adherence and acute hospitalization rates (emergency department [ED] and inpatient [IP]) were compared at baseline versus one-year post-intervention using paired t-test or signed-rank tests. Repeated measures analysis of variances detected the interaction effect of time by intervention group after controlling for sociodemographic covariates. RESULTS: Member profiles in SEPA (n = 2 796) and LCNWPA (n = 793) were racially and ethnically distinct. Both cohorts experienced statistically significant improvements in mean PDC rate (+4.9% and +7.2%; p = 0.01 and p = 0.03, respectively), accompanied by significant reductions in ED visits (asthma-related: -23.0% and -17.5%, respectively; p < 0.01), and IP admissions (asthma-related: -37.1% and -40.0%, respectively; p < 0.01). The PI subcohorts showed significantly greater improvements in mean PDC versus GI subcohorts (p ≤ 0.04), whereas acute hospitalization rates were statistically comparable in the SEPA cohort, despite its greater asthma burden. CONCLUSIONS: Managed care-led interventions can effectively improve medication adherence and reduce acute hospitalizations in high-risk Medicaid populations.

Adherence and Concomitant Medication Use among Patients on Warfarin Therapy: Insight from a Large Pharmacy Dispensing Database in Japan.

Warfarin is a drug used for anticoagulation management, with a narrow therapeutic range and multiple drug-drug interactions. Adherence and proper use of concomitant medication are thus fundamental to the efficacy and safety of warfarin therapy. In 2012, we retrospectively analyzed data from three large-scale pharmacy chains in Japan. We included all adults (≥ 20 years old) with at least one record of warfarin dispensation. We examined patient demographic data, adherence as measured by medication possession ratio (MPR), and co-dispensation focusing on the number of concomitant dispensations and concurrent use of medications that increase bleeding risk. Thresholds of underadherence and overadherence were set at <0.9 and >1.1, considering the narrow therapeutic window. We reviewed 443007 warfarin dispensation records of 71340 individuals (median age, 73 years; 62% male). The MPR was 1.0 (interquartile range: 0.96-1.0), and underadherence and overadherence was found in 16.3 and 1.9% of individuals, respectively. The median number of co-dispensed drugs was eight at each pharmacy encounter, which did not differ by age group. Drugs associated with a high bleeding risk were dispensed in 40.0% of encounters and accounted for 16.4% of all co-dispensed drugs. In summary, we found optimal overall adherence, as assessed by MPR, among our Japanese study population, even when defining a strict cut-off value. However, polypharmacy was common in all age groups and medications with a high bleeding risk profile were often co-dispensed with warfarin. Future research addressing how these dispensation patterns affect patient outcome is warranted.

In search of a standard when analyzing medication adherence in patients with heart failure using claims data: a systematic review.

To determine and address medication non-adherence is important and may improve patient outcomes. Our aim was to perform a systematic review on the operationalization of adherence measures in patients with heart failure using claims data. We searched the MEDLINE, EMBASE, and Cochrane databases. A quality check of the full-text articles was performed using the Quality in Prognosis Studies tool. We included 28 studies. Eleven studies used the medication possession ratio, 15 the proportion of days covered, and six studies used own methods to calculate medication adherence. Almost all studies used an observation period of 1 year. Twenty-one studies considered angiotensin converting enzyme inhibitors or angiotensin receptor antagonists, 17 beta-blockers, 11 diuretics, eight mineralocorticoid receptor antagonists, six digitalis-glycosides, and six statins. Eight studies looked at single substance classes; 18 studies analyzed more than one drug class. Different assumptions for the dosage were used. In seven studies, switching within therapeutic classes was allowed. Three studies allowed stockpiling, nine studies censored hospital stays, and four studies censored death. Seventeen studies dichotomized the results, applying the cutoff ≥ 0.8 to define a patient as adherent. Eight studies analyzed adherence as a continuous value. The reporting quality of the methodology applied varied widely between studies. A gold standard is currently not available for the quantification of medication adherence in patients with chronic heart failure via claims data. To assess the methodology, the following parameters should be described: method of measurements, observation period, substances, dosing, switches, stockpiling, truncations, statistical analysis, and cutoff for adherence.

Impact of hospitalization on medication adherence estimation in claims data.

WHAT IS KNOWN AND OBJECTIVE: Pharmacy claims are commonly used to assess medication adherence. It is unclear how different approaches to handling hospitalizations compare to the gold standard of using outpatient and inpatient drug data. This study aimed to compare the impact of different approaches to handling hospitalizations on medication adherence estimation in administrative claims data. METHODS: We identified ß-blocker initiators after myocardial infarction (MI) and statin initiators regardless of hospitalization histories in the population-based, Taiwan database, which includes outpatient and inpatient drug claims data. Adherence to ß-blockers or to statins during a 365-day follow-up period was estimated in outpatient pharmacy claims using the proportion of days covered (PDC) in three ways: ignoring hospitalizations (PDC1); subtracting hospitalized days from the denominator (PDC2); and assuming drug use on all hospitalized days (PDC3). We compared these to an approach that incorporated inpatient drug use (PDC4). We also used a hypothetical example to examine variations across approaches in several scenarios, such as increasing hospitalized days. RESULTS AND DISCUSSION: Mean 365-day PDC was 74% among 1729 post-MI ß-blocker initiators (range: 73.1%-74.9%) and 44% among 69 435 statins initiators (range: 43.5%-44.0%), which varied little across approaches. Differences across approaches increased with increasing number of hospitalized days. For patients hospitalized for >28 days, mean difference across approaches was >15%. PDC3 consistently yielded the highest value and PDC1 the lowest. WHAT IS NEW AND CONCLUSIONS: On average, different approaches to handling hospitalizations lead to similar adherence estimates to the gold standard of incorporating inpatient drug use. When patients have many hospitalization days during follow-up, the choice of approach should be tailored to the specific setting.

Predialysis Cardiovascular Disease Medication Adherence and Mortality After Transition to Dialysis.

BACKGROUND: Medication nonadherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of predialysis medication adherence among patients with advanced chronic kidney disease and mortality following their transition to dialysis. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 32,348 US veterans who transitioned to dialysis during 2007 to 2011. PREDICTORS: Adherence to treatment with cardiovascular drugs, ascertained from pharmacy database records using proportion of days covered (PDC) and persistence during the predialysis year. OUTCOMES: Post-dialysis therapy initiation all-cause and cardiovascular mortality, using Cox models with adjustment for confounders. RESULTS: Mean age of the cohort was 72±11 (SD) years; 96% were men, 74% were white, 23% were African American, and 69% had diabetes. During a median follow-up of 23 (IQR, 9-36) months, 18,608 patients died. Among patients with PDC>80%, there were 14,006 deaths (mortality rate, 283 [95% CI, 278-288]/1,000 patient-years]); among patients with PDC>60% to 80%, there were 3,882 deaths (mortality rate, 294 [95% CI, 285-304]/1,000 patient-years); among patients with PDC≤60%, there were 720 deaths (mortality rate, 291 [95% CI, 271-313]/1,000 patient-years). Compared with patients with PDC>80%, the adjusted HR for post-dialysis therapy initiation all-cause mortality for patients with PDC>60% to 80% was 1.12 (95% CI, 1.08-1.16), and for patients with PDC≤60% was 1.21 (95% CI, 1.11-1.30). In addition, compared with patients showing medication persistence, adjusted HR risk for post-dialysis therapy initiation all-cause mortality for patients with nonpersistence was 1.11 (95% CI, 1.05-1.16). A similar trend was detected for cardiovascular mortality and in subgroup analyses. LIMITATIONS: Large number of missing values; results may not be generalizable to women or the general US population. CONCLUSIONS: Predialysis cardiovascular medication nonadherence is an independent risk factor for postdialysis mortality in patients with advanced chronic kidney disease transitioning to dialysis therapy. Further studies are needed to assess whether interventions targeting adherence improve survival after dialysis therapy initiation.

Estimation of optimal adherence threshold for tumor necrosis factor inhibitors in rheumatoid arthritis.

INTRODUCTION: Optimal adherence thresholds can vary across medications and disease states. The objective of the study was to determine the optimal threshold of the proportion of days covered (PDC) for tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA). METHODS: Patients with RA initiating self-administered TNF inhibitors were identified using 2012-18 Medicare fee-for-service claims. Time-varying PDC was calculated every day for the preceding 90 days during follow-up. Oral and injected glucocorticoid use, hospitalizations, emergency room (ER) visits, serious infections, and a composite of these were measured as outcomes. Time to first occurrence of each outcome as a function of time-varying PDC for TNF inhibitors was evaluated using Cox regression. Incident/dynamic time-dependent receiver operating characteristic curves and Youden's J index were used to obtain the optimal PDC threshold for outcomes at 365 days. RESULTS: Of the 1190 patients who met the study inclusion criteria, almost 75% (865 patients) experienced at least one of the outcomes. Increasing PDC by 10% was significantly associated with decreased risks of the composite outcome (HR 0.98, 95% CI 0.96-1.00), oral glucocorticoid use (HR 0.93, 95% CI 0.91-0.96), and hospitalization (HR 0.96, 95% CI 0.94-0.99) but an increased risk of ER visits (HR 1.04, 95% 1.01-1.07). Optimal PDC thresholds for the composite outcome, oral glucocorticoid use, and hospitalization were 0.64, 0.59, and 0.56, respectively. CONCLUSIONS: Increased PDC was associated with a decreased risk of adverse outcomes, except ER visits. The optimal PDC for TNF inhibitors in Medicare patients with RA based on clinical outcomes was about 60%. Key Points • The optimal proportion of days covered threshold for tumor necrosis factor inhibitors at 365 days based on clinical outcomes was found to be about 60%, which is lower than the traditional 80% used to define adherence. • Increased adherence was associated with decreased risks of oral glucocorticoid use, hospitalization, and the composite outcome. However, it was also associated with an increased risk of emergency room visits. • The mean time-varying 90-day proportion of days covered decreased throughout the study starting 92% at day 1 of follow-up to 62% at day 365.

Digging in real-word electronic database for assessing CDK 4/6 inhibitors adherence in breast cancer patients from Romania.

Introduction: It is imperative for patients to respect the prescribed treatments to achieve the anticipated clinical outcomes, including the outpatients receiving oral anti-cancer drugs such as selective cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). With the introduction of three CDK 4/6i drugs in the Romanian pharmaceutical market in 2018, our study aimed to evaluate medication adherence and the influencing factors among patients undergoing treatment with palbociclib, ribociclib, or abemaciclib for advanced or metastatic breast cancer. Methods: Medication adherence was assessed using the Proportion of Days Covered (PDC) method, and Spearman correlation analysis was conducted to explore the relationships between adherence, age, gender, and follow-up duration. Results: The study enrolled 330 breast cancer patients, with an average follow-up period of 14.6 ± 12.5 months for palbociclib, 10.6 ± 7.1 months for ribociclib, and 8.6 ± 6.4 months for abemaciclib-treated patients. A small proportion of patients demonstrated non-adherence: 12.8% for palbociclib, 14.6% for ribociclib, and 14.7% for abemaciclib. Among patients receiving palbociclib, there was no significant correlation between adherence, age (rho = 0.07, p = 0.35), or gender (rho = -0.144, p = 0.054). However, a significant correlation was found with the duration of follow-up (rho = -0.304, p < 0.0001). Similar results were observed for patients receiving ribociclib or abemaciclib. Most patients received combination therapy with letrozole (46%) and exemestane (13%) for palbociclib, letrozole (48%) and fulvestrant (19%) for ribociclib, and fulvestrant (39%) and letrozole (27%) for abemaciclib, Discussion: High adherence rates were observed among patients treated with CDK 4/6i drugs, with no significant differences noted among the three drugs in this class. However, the collected patient data was limited, lacking information on adverse reactions that could potentially lead to treatment discontinuation, as determined by the oncologist's decision not to prescribe. Consequently, a comprehensive understanding of all factors contributing to the low adherence levels is hindered.

Evaluation of Adherence and Persistence to Triple Therapy in Patients with COPD: A German Claims Data Study.

Purpose: Triple therapy (long-acting muscarinic antagonist/long-acting ß2-agonist/inhaled corticosteroid) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence. This study assessed comparative adherence and persistence to single-inhaler triple therapy (SITT) versus MITT among patients with COPD in a real-world setting in Germany. Patients and Methods: This retrospective analysis using the WIG2 benchmark database identified patients with COPD newly initiating triple therapy with MITT or SITT (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or formoterol/beclomethasone/glycopyrronium bromide [FOR/BDP/GLY]) November 2017-June 2019. Eligible patients were ≥35 years with 1 year's continual insurance prior to triple therapy initiation and no previous record of triple therapy. Inverse probability of treatment weighting was used to balance baseline characteristics. Adherence was measured using proportion of days covered (PDC) at 6, 12, and 18 months post-treatment initiation; persistence (time until treatment discontinuation) was measured at 6, 12, and 18 months, with a gap of >30 days used to define non-persistence. Results: Of 5710 patients included in the analysis (mean age 66 years), 71.4% initiated MITT and 28.6% initiated SITT (FF/UMEC/VI: 41.4%; FOR/BDP/GLY: 58.6%). Mean PDC was higher among SITT versus MITT users at all time points; at each time point, mean PDC was highest among FF/UMEC/VI users. During the first 6 months following treatment initiation, higher adherence was exhibited by FF/UMEC/VI (29%) and FOR/BDP/GLY (19%) users versus MITT users. Over the entire observation period, FF/UMEC/VI users had the highest proportion of persistent patients; at 18 months, 16.5% of FF/UMEC/VI users were persistent versus 2.3% of MITT users. Conclusion: Patients initiating SITT in Germany had significantly higher adherence and persistence compared with patients initiating MITT over 6 to 18 months following treatment initiation. Among SITT, FF/UMEC/VI users had the highest proportion of adherence and persistence.

Treatment patterns and factors associated with adherence in pulmonary arterial hypertension.

OBJECTIVE: Improving understanding of actual pulmonary hypertension (PH) treatment adherence patterns is crucial to properly treating these patients. We aimed to primarily assess adherence to treatments used for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) specific therapies, identify potential factors related to it and secondly describe its treatment patterns. METHODS: A 6-month observational cross-sectional study in a tertiary care hospital was conducted. Patients with PH-targeted therapy who picked it up in the ambulatory hospital pharmacy and who had been on treatment with the same drug for at least 1 year were included. Adherence was assessed as: 1) Proportion of days covered (PDC); and 2) Simplified Medication Adherence Questionnaire (SMAQ). PDC ≥80% was considered adherent. Statistical analyses were performed to evaluate the study outcomes. Logistic regressions were estimated to identify the association between baseline characteristics and factors associated with adherence. P < 0.05 indicated statistical significance. RESULTS: A total of 63 patients with 127 different treatments were included, 71.4% were females with a mean age (SD) of 59 (15) years. PAH was the most common diagnosis (74.6%). Double therapy was used in 39.7% of patients, being the combination of Macitentan + Tadalafil and Ambrisentan + Tadalafil the most prescribed. Endothelin receptor antagonists were the most used treatment (40.2%). Adherence according to PDC was 93.7%, showing no great differences depending on the targeted drug used, and according to SMAQ 61.9%. The agreement degree of both methods was slight (65.1%; Kappa 0.12). Only female sex (OR: 0.23, 95% CI: 0.06-0.90; p = 0.035) was associated with worse adherence in the SMAQ method but not in the PDC. Adverse events were reported by a 55.6% of participants and the perception of effective treatment was high (95.2%). CONCLUSIONS: Adherence to PH therapy differs depending on the assessment method; PDC showed greater adherence rate than SMAQ. According to SMAQ, female sex may have a negative impact on adherence in this cohort, but PDC revealed no factors influencing it. No notable differences in adherence between treatment types were found and generally patients felt the treatments were effective in controlling their disease.

[Analysis of medication adherence using electronic prescriptions in a community pharmacy: 'REACT' study]. / Análisis de la adherencia farmacológica utilizando la receta electrónica en una farmacia comunitaria: estudio 'REACT'.

Background: Patients` lack of adherence to pharmacological treatments has a major impact, both clinical and economical. While different methods are used to measure adherence, retrospective studies are being used more frequently as they are more objective, less prone to bias by patient perception and interfere less with patients' lives. The electronic prescription system provides the community pharmacy with a useful tool to conduct this research. Objective: To measure the adherence of patients to their chronic medication considering different therapeutic drug groups and their mental health using electronic prescription information available in a database. Methods: An observational, ambispective and logitudinal study was developed for 300 patients. Adherence was assessed using Proportion of Days Covered (PDC) per patient and per treatment and the Morisky Green Levine test. Data on patients' dispensed medication for the last 12 months was obtained through the electronic prescription system. Data on patient mental health was gathered using the PHQ-2 screen for depression. Results: A total of 300 patients were recruited, but only 290 were included in the analysis. 25.5%; [95%CI: 20.6:30.9] were classified as polymedicated. The median PDC per patient was 0.90 (IQR: 0.73 - 1). According to the Morisky Green Levine questionnaire, 57.9% of the patients [95%CI 52.0:63.6] adhered to their treatments. Concurrence between the Morisky Green Levine test and the PDC had a kappa k=0.086. Conclusion: The electronic prescription turned out to be a useful tool to gain insight into adherence to long-term treatments measured in terms of the PDC.

Adherence to and persistence with lacosamide, perampanel, lamotrigine, and levetiracetam in adult patients with focal epilepsy in Japan: A descriptive cohort study using a claims database.

Objective: We evaluated adherence to and 1-year persistence of two third-generation anti-seizure medications (ASMs), lacosamide and perampanel, in adult patients with focal epilepsy, compared with lamotrigine and levetiracetam. Methods: A cohort study was conducted using a Japanese health insurance claims database (JMDC Inc.). We identified patients with adult-onset focal epilepsy who initiated any of the four ASMs between August 31, 2016, and October 31, 2019. Patients were further classified into ASM-naïve patients initiating any of the four ASMs as first-line treatment, and ASM-experienced patients initiating any of the four ASMs as second- or later-line treatment. Outcomes included adherence (proportion of days covered [PDC], defined as the total number of days covered by ASMs divided by the total number of days in the follow-up period) and 1-year persistence for the four ASMs. Results: We identified 141 lacosamide, 75 perampanel, 80 lamotrigine, and 530 levetiracetam initiators. Among these, the proportion of ASM-naïve patients was highest in the levetiracetam group (60.8%), followed by the lamotrigine (25.0%), lacosamide (20.6%), and perampanel groups (1.3%). Mean PDC (standard deviation) was similar across the four groups, at 0.95 (0.08) for lacosamide, 0.93 (0.12) for perampanel, 0.92 (0.10) for lamotrigine and 0.94 (0.11) for levetiracetam. The proportion of patients persisting with treatment for 1 year was highest in the lacosamide group (73.0%), followed by the levetiracetam (58.3%), lamotrigine (57.5%), and perampanel groups (54.7%). In ASM-naïve patients, adherence and 1-year persistence were almost identical in the lacosamide, lamotrigine, and levetiracetam groups. Results for ASM-experienced patients did not significantly differ from those of all patients. Significance: With regard to adherence and 1-year persistence, lacosamide may be equal to or better than lamotrigine and levetiracetam, especially in patients with experienced ASM, while perampanel may be comparable to lamotrigine and levetiracetam in patients with experienced ASM.