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Introduction: Phosphorodiamidate morpholino oligomers (PMOs), weight-based treatments administered weekly by intravenous infusion, are approved in the US for patients with Duchenne muscular dystrophy (DMD) amenable to certain exon skipping. Evidence regarding PMO treatment patterns in real-world settings is limited. This study used longitudinal administrative claims data to characterize PMO treatment patterns among US patients with DMD., Methods: MarketScan ® commercial and Medicaid data (January 1, 2018-December 31, 2021) were used to identify claims for PMO treatments (eteplirsen, golodirsen, viltolarsen, casimersen). The proportion of days covered (PDC), proportion with continuous PMO claims coverage (no gaps in claims ≥ 30 days), and time to subsequent PMO claims after a ≥ 30-day gap in PMO claims were described., Results: One hundred thirty-three patients with ≥ 1 PMO claim were identified. Multiple codes were needed to identify PMO treatment coverage. Mean age was 14.1 years; all patients were male. Mean continuous follow-up duration was 669.3 days. Median PDC was 83.4%. Seventy-four (55.6%) patients had continuous PMO claims coverage (no ≥ 30-day gaps in claims). Of the 59 patients with ≥ 1 gap in PMO claims of ≥ 30 days, 39 had ≥ 1 subsequent PMO claim. Accounting for censoring via Kaplan-Meier analysis, 75.5% had a subsequent PMO claim within 1 year after a ≥ 30-day gap, with a median time of 64 days (including the qualifying 30 days)., Conclusion: Understanding treatment patterns is important for characterizing real-world utilization of precision genetic medicines. This study observed a high PDC for PMO treatments for DMD. Most patients had continuous PMO claims coverage, and most patients with a gap in PMO claims had a subsequent PMO claim. Nonetheless, the observed persistence may have been underestimated given shortcomings of claims data and payer coverage considerations. Caution should be exercised when inferring treatment effectiveness or tolerability based on observed treatment patterns from claims data alone for weight-based, infused PMO treatments., Competing Interests: Declarations Conflict of Interest James Signorovitch is an employee of Analysis Group, Inc., which has received consulting fees from Sarepta Therapeutics, Inc. Alexa C. Klimchak, Bryan Innis, and Katherine Gooch are employees of Sarepta Therapeutics, Inc., and may own stock/options in the company. Chamindra G Laverty declares contracts (as principal investigator) from Sarepta Therapeutics, Dyne Therapeutics, Avidity Biosciences, FibroGen, Scholar Rock, Novartis Gene Therapies, and Biohaven; consulting fees from Sarepta Therapeutics (payments to her institution), NS Pharma (payments to herself), and Avidity (payments to her institution), Catalyst (payments to herself), SolidBio (payments to herself), Novartis (payments to herself), Biogen (payments to herself); and support for attending meetings and/or travel from the Muscular Dystrophy Association, CureCMD, and CureSMA. Ethical Approval MarketScan® data included in this study were provided by and used with permission from Merative™. Institutional review board approval was not required to conduct this study, as data were de-identified and compliant with Health Insurance Portability and Accountability Act (HIPAA) regulations., (© 2024. The Author(s).)

Introduction: Associations between increased functional disability and higher healthcare resource utilization (HCRU) and costs were reported in patients with psoriatic arthritis (PsA). We assessed characteristics/outcomes of patients with PsA receiving tofacitinib monotherapy vs combination therapy with conventional synthetic disease-modifying antirheumatic drugs., Methods: Claims data from Optum ® Clinformatics ® Data Mart (OC) and Merative™ MarketScan ® (MS) databases between December 2017 and February 2020 were analyzed. Outcomes assessed were adherence/persistence by therapy type (monotherapy/combination therapy); HCRU/costs (per patient per month) by periods on-treatment (sum time on tofacitinib) and off-treatment (sum time off tofacitinib [gap of > 60 days]) plus therapy type., Results: This analysis included 274 and 395 tofacitinib-treated patients in OC (70.4% female, mean age 54.4 years) and MS (68.9% female, mean age 51.4 years), respectively. Percentages of patients with a proportion of days covered ≥ 0.8 at 12 months for monotherapy vs combination therapy were OC, 44.5% vs 53.8%; MS, 36.4% vs 45.7%. Generally similar trends were seen over 24 months and for medication possession ratio ≥ 0.8. Median (95% confidence interval) times to treatment discontinuation for monotherapy vs combination therapy were OC, 10.1 (7.4-11.8) vs 16.7 (8.3-26.6) months; MS, 6.9 (5.6-9.4) vs 11.0 (6.1-13.9) months. During off-treatment vs on-treatment periods, numerical decreases were observed for all-cause (OC, $5383 vs $6149; MS, $4145 vs $5180) and PsA-related costs (OC, $3237 vs $4515; MS, $2703 vs $3907) regardless of therapy type. During off-treatment vs on-treatment periods, numerical increases in outpatient visits for all-cause (OC, 2.37 vs 2.05; MS, 2.15 vs 1.99) and PsA-related visits (OC, 0.60 vs 0.46; MS, 0.47 vs 0.44) were observed, and PsA-related medications numerically decreased (OC, 1.21 vs 1.53; MS, 1.05 vs 1.48)., Conclusion: In this USA-based claims analysis, tofacitinib adherence was numerically lower for patients with PsA receiving monotherapy vs combination therapy. Costs numerically decreased off-treatment vs on-treatment, irrespective of therapy type, driven by lower medication costs., (© 2024. The Author(s).)

Introduction: Biologic disease-modifying anti-rheumatics drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are important treatments for rheumatoid arthritis (RA). As more of these drugs become available, there is a greater need to assess their real-world adherence and drug survival. Methods: Treatment-naïve and treatment-experienced patients with RA who initiated treatment with bDMARDs and tofactinib during 2015–2018 in a large Israeli health maintenance organization were included. Adherence and time to treatment suspension were recorded. Odds for adherence were estimated using a multivariable logistic regression model. Risk for treatment suspension was estimated using a mixed-effect Cox proportional hazard model. Results: The analysis included 753 eligible patients (61.8% treatment-naïve) treated with 1287 treatment episodes (tofacitinib 24.2%, tocilizumab 17.5%, etanercept 16.0%, adalimumab 10.4%, abatacept 9.9%, rituximab 9.0%, golimumab 6.9%, certolizumab pegol 3.6%, infliximab 1.9%, and sarilumab 0.5%). Good adherence was measured for almost all drugs, yet over 50% of all treatment episodes were suspended. Older age was associated with reduced risk for treatment suspension while higher number of primary care visits and higher Charlson's comorbidity score were associated with increased risk. Compared to etanercept, treatment with adalimumab, certolizumab, or rituximab was associated with increased risk for treatment suspension (HR 1.68 95% CI 1.27–2.22, HR 1.62 95% CI 1.00–2.60, and HR 2.72 95% CI 2.02–3.67, respectively). Conclusion: Treatment choice primarily depends on disease activity and prognosis. Real-world data, showing differences in drug survival of bDMARDs and tsDMARD, can also be used in the variety of considerations when choosing treatment. Future studies could separate patients with RA into subgroups, which would also account for potential drug survival differences and enable personalized therapy. [ABSTRACT FROM AUTHOR]

Introduction: Treatment persistence for anticoagulant therapy is important in preventing thromboembolism in nonvalvular atrial fibrillation (NVAF) patients. Understanding drug utilization pattern and treatment changes in oral anticoagulant (OAC) users may facilite better NVAF management. Thus, our study aimed to examine OAC treatment patterns preceding events leading to switch or discontinuation and medication adherence in Korean NVAF patients. Methods: We conducted a drug utilization study on all Korean patients with atrial fibrillation (AF) newly prescribed OACs between July 2015 and November 2016 using the national claims data. We assessed treatment changes such as switching and discontinuation from index OAC and relevant events preceding the change and examined patient characteristics as predictors of changes that occurred among OAC users. Medication adherence was compared among OAC users by calculating the medication possession ratio (MPR). Results: A total of 48,389 NVAF patients were identified who initiated OACs within the study period. Most initiated nonvitamin K antagonist oral anticoagulants (NOACs) (22% apixaban, 24% dabigatran, 37% rivaroxaban), and 18% initiated warfarin. The frequency of switch to another OAC was 8.8% for apixaban, 16.1% for dabigatran, 6.6% for rivaroxaban, and 19.1% for warfarin. The frequency of discontinuation was lower for apixaban (22.9%), dabigatran (26.3%), and rivaroxaban (25.7%) than warfarin (31.6%). Compared to warfarin, NOAC users were less likely to switch treatment. Thromboembolic event was the most common clinical event preceding switch from warfarin to NOAC and from NOAC to warfarin. Discontinuation of OAC was often preceded by a bleeding event. Patients who initiated apixaban showed significantly higher mean MPR compared to those on dabigatran and warfarin. Conclusion: In real-world practice in Korea, we have observed treatment change to be common in OAC users. Our results indicate better medication adherence with NOACs than with warfarin. (ClinicalTrials.gov registration number NCT03572972). Plain language summary: Anticoagulants are drugs that thin blood with the purpose of preventing thromboembolic disease (e.g., stroke), which is a disease occurring when a blood clot forms or blocks vessel. Maintaining treatment for anticoagulation is important to prevent stroke in atrial fibrillation (AF) patients. To understand current drug usage pattern and treatment changes related to oral anticoagulants (OAC) we examined OAC treatment patterns and preceding events that led to drug switch or stop and medication maintenance by Korean AF patients. The study was conducted by utilizing the Korean national claims data from July 2015 to November 2016. All AF patients who newly started taking OAC were included in the analysis. In total, 48,389 patients were identified with most (83%) taking nonvitamin K antagonist oral anticoagulants (NOAC), which are newer generation blood thinners, including apixaban, dabigatran, and rivaroxaban, and 18% taking warfarin, the conventional blood thinner. Compared to warfarin, NOAC users were less likely to switch to other treatment. NOAC users discontinued the treatment less frequently than warfarin users. Thromboembolic events commonly preceded switch between OACs. Patients who stopped taking OACs were often confronted with a bleeding event before stopping treatment. Apixaban takers showed higher treatment persistence compared to dabigatran or warfarin users. In this study, we determined that treatment change is common in OAC-using patients. The results suggest that NOAC users may better adhere to treatment than warfarin users. [ABSTRACT FROM AUTHOR]

Introduction: Although antimuscarinics form the first-line therapy in overactive bladder (OAB), little is known regarding antimuscarinic discontinuation among OAB patients in nursing homes. This study examined treatment patterns and predictors of antimuscarinic discontinuation among long-term nursing home (LTNH) residents with OAB. Methods: The study cohort included LTNH residents (defined as residents staying ≥ 101 consecutive days) from the Minimum Data Set linked 2013–2015 Medicare claims data. Patients with OAB were defined by OAB-related claims and medication codes. Treatment patterns and discontinuation (medication gap ≥ 30 days) were characterized by examining OAB-specific antimuscarinics prescribed during LTNH stays. The Andersen Behavioral Model was used to identify predisposing, enabling and need factors that predict discontinuation. Kaplan-Meier curves and multivariable Cox proportional hazards regression model were used to assess the unadjusted and adjusted times to discontinuation, respectively, among different antimuscarinics. Results: The mean age of the study cohort (n = 11,012) was 81.6 years (± 8.5), 74.6% were female, and 89.8% were non-Hispanic White. The mean duration of nursing home stay was 530.1 (± 268.4) days. The most commonly prescribed OAB-specific antimuscarinic was oxybutynin (69.8%). Overall, 66.5% of the study cohort discontinued the index antimuscarinic. Multivariable Cox PH regression analysis revealed that compared to LTNH residents who initiated treatment with oxybutynin, treatment discontinuation was lower with solifenacin or fesoterodin and discontinuation was more frequent when treatment was initiated with tolterodine, darifenacin or trospium compared with oxybutynin. In addition, several need factors (comorbidities, medication use and anticholinergic burden, etc.) were associated with antimuscarinic discontinuation. Conclusion: About two-thirds of LTNH residents with OAB discontinued their index antimuscarinic during their nursing home stay. There was significant variation in discontinuation based on the index antimuscarinic agent with lowest risk of discontiuation with solifenacin and fesoterodin. Concerted efforts to optimize antimuscarinic use are needed to improve the management of OAB in nursing homes. [ABSTRACT FROM AUTHOR]

Introduction: Patients' adherence to and persistence on treatment for inflammatory bowel disease (IBD) can vary, depending on type and distribution of disease and treatment modality. We aim to identify differences in adherence and persistence with treatments with different administration routes (intravenous vs oral) in IBD.Methods: A retrospective cohort analysis of a claims database of adult patients diagnosed with IBD or rheumatoid arthritis (RA) who began treatment with vedolizumab, tofacitinib, or infliximab from January 2015 through December 2015. Adherence evaluated by proportion of days covered (PDC) and cumulative days with gaps at least 20% beyond expected interval (CG20) using multivariable generalized linear equation models. Persistence assessed as time to treatment discontinuation over 12 months of follow-up using Kaplan-Meier estimates and Cox proportional hazards models; proportion of persistent patients determined via multivariable logistic regression. Indirect comparisons across disease states adjusted using infliximab data.Results: After indirect adjustment by disease, mean PDC difference was significantly higher (difference of 4.7%; P = 0.0376) and mean CG20 was lower (difference of 15 days; P = 0.0646) but not statistically significant in vedolizumab/IBD than tofacitinib/RA.Conclusion: We describe a novel adjustment method for interdisease treatment differences using infliximab treatment patterns to bridge differences between IBD and RA. After adjustment, adherence was higher with infusions than oral medications, which may affect outcomes. Indirect comparisons between vedolizumab and tofacitinib are not generalizable and should be confirmed in tofacitinib-treated IBD patients.Funding: Takeda Pharmaceuticals U.S.A., Inc. [ABSTRACT FROM AUTHOR]

Introduction: Different prolonged-release formulations of tacrolimus are available. To date, the pharmacokinetic (PK) profile of LCP-tacrolimus (LCPT; Envarsus®) has not been compared with PR-Tac (Advagraf®) in de novo kidney transplant recipients. These profiles will guide clinical recommendations for the initiation and dose titration strategies of once-daily tacrolimus formulations.Methods: This randomized, parallel-group, open-label, multicenter PK study randomized 75 de novo, adult, white kidney transplant recipients to LCPT 0.17 mg/kg/day (n = 37) or PR-Tac 0.20 mg/kg/day (n = 38) for 4 weeks. Dose adjustments were permitted to target a pre-defined therapeutic range based on measured trough blood concentrations.Results: PK analysis (days 1, 3, 7 and 14) included 68 patients (LCPT, n = 33; PR-Tac, n = 35). Similar proportions of patients were within the pre-defined therapeutic tacrolimus trough blood concentration range, with < 12% in each group having below-target trough levels over the study period. LCPT demonstrated ~ 30% greater relative bioavailability [LCPT/PR-Tac adjusted geometric mean ratio: day 3, 1.32 (p = 0.007); day 7, 1.25 (p = 0.051); day 14, 1.43 (p = 0.002)] and ~ 30% lower peak-to-trough percentage fluctuation of blood concentration [LCPT/PR-Tac adjusted geometric mean ratio: day 3, 0.70 (p < 0.001); day 7, 0.68 (p < 0.001); day 14, 0.73 (p = 0.004)] in addition to longer time to maximum blood concentration (tmax), lower maximum concentration (Cmax) and a consistently lower daily dose (~ 40% dose reduction with LCPT vs. PR-Tac by day 28). Safety profiles were similar.Conclusion: In de novo kidney transplant recipients, prolonged-release formulations of tacrolimus can reach therapeutic concentrations in the immediate post-transplant period. LCPT has greater relative bioavailability and lower peak-to-trough fluctuation compared with PR-Tac.Trial Registration: Registered at ClinicalTrials.gov; study number NCT02500212.Funding: Chiesi Farmaceutici S.p.A. [ABSTRACT FROM AUTHOR]

Introduction: Adherence to diabetes medication has been linked to improved glycemic levels and lower costs, but previous research on adherence has typically involved oral antidiabetic medication or insulin. This study examines how adherence and persistence to once-daily liraglutide impact glycemic control and economic outcomes in a real-world population of adult type 2 diabetes (T2D) patients. Methods: A retrospective cohort study using administrative claims data from July 2009 through September 2013. Patients aged ≥18 years with T2D treated with liraglutide were identified (index date = first liraglutide prescription). Adherence was based on the proportion of days covered (PDC); with PDC ≥0.80 classified as adherent. Non-persistent patients were those with a gap in therapy of >90 days. Lab results for glycated hemoglobin (A1C) were used to identify whether patients achieved target levels of <7.0% and ≤ 6.5%, or experienced a reduction of ≥1.0% in A1C from pre-index (baseline) to post-index (follow-up). Logistic regression was used to estimate the likelihood of achieving the A1C goals, adjusted for baseline characteristics. Diabetes-related medical, pharmacy, and total costs were modeled and estimated for the adherence and persistence cohorts. Results: A total of 1321 patients were identified. The mean PDC was 0.59 and 34% of patients were classified as adherent, while 60% were persistent over 12 months of follow-up. Adherent and persistent patients were more likely to achieve each of the A1C goals than their non-adherent and non-persistent counterparts after adjusting for patient characteristics. Adherence and persistence were associated with higher adjusted diabetes-related pharmacy and total healthcare costs during follow-up; whereas persistent patients had significantly lower diabetes-related medical costs than non-persistent patients. Conclusions: Adherence and persistence to liraglutide are associated with improved A1C outcomes. Persistent patients showed significantly lower medical costs versus those discontinuing liraglutide. Total healthcare costs were higher for adherent and persistent cohorts driven by higher pharmacy costs. [ABSTRACT FROM AUTHOR]

Introduction: Greater adherence to medications has been broadly demonstrated to be associated with improved clinical outcomes. However, there is limited real-world evidence on adherence to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes mellitus (T2DM). Methods: This retrospective cohort study used United States administrative claims data to compare adherence to GLP-1RAs in T2DM patients initiating exenatide once weekly (QW), exenatide twice daily (BID), or once-daily liraglutide (initiated therapy = index therapy). Patients were included if they had T2DM, were GLP-1RA-naïve, initiated a GLP-1RA from 02/01/2012-01/31/2013 (date of initiation = index), were ≥18 years at index, and had continuous enrollment for 12 months before (baseline) to 6 months after index (follow-up). Study outcome was index GLP-1RA adherence (proportion of days covered [PDC] during follow-up, dichotomized at ≥80% vs. <80%, and at ≥90% vs. <90%). Multivariable logistic regressions compared adherence between the GLP-1RAs, adjusting for potential confounders. Sensitivity analyses were performed separating liraglutide by dose (1.2 mg/1.8 mg). Results: Study sample included 4,041 exenatide QW, 4,586 exenatide BID, and 14,211 liraglutide (6,641 1.2 mg, 7,570 1.8 mg) patients. Median unadjusted PDC values were 0.783 for exenatide QW, 0.500 exenatide BID, 0.722 liraglutide, 0.761 liraglutide 1.2 mg, and 0.683 liraglutide 1.8 mg. Compared with patients treated with either exenatide BID or liraglutide, patients treated with exenatide QW had a statistically significantly greater multivariable-adjusted odds of achieving adherence of ≥80% (odds ratio vs. exenatide QW (OR) = 0.41 for exenatide BID; 0.80, liraglutide; 0.87, liraglutide 1.2 mg; 0.75, liraglutide 1.8 mg) and ≥90% (OR = 0.31 for exenatide BID; 0.60 liraglutide; 0.66 liraglutide 1.2 mg; 0.56 liraglutide 1.8 mg) (all P < 0.001). Conclusion: Patients initiating exenatide QW had significantly higher adjusted odds of adherence compared with patients initiating other GLP-1RAs. Given differences in adherence across the GLP-1RAs, research correlating these factors with clinical and economic outcomes is warranted. [ABSTRACT FROM AUTHOR]