Characteristics and lipid lowering treatment patterns in patients tested for lipoprotein(a): A real-world US study.

Objective: Elevated lipoprotein(a) [Lp(a)] is a risk factor for atherosclerotic cardiovascular disease (ASCVD) and has no approved pharmacotherapies. Limited real-world data exists on the proportion of patients with available Lp(a) test results, characteristics of these patients, and their use of lipid lowering therapies (LLTs) for secondary prevention (SP) and primary prevention (PP) of ASCVD. Methods: Patients with measured Lp(a) receiving LLTs for SP or PP of ASCVD were identified in the Optum Clinformatics® Data Mart database. Lp(a) distribution and LLT utilization including persistence and adherence were assessed. Logistic regression was used to assess the association between Lp(a) levels and low-density lipoprotein cholesterol (LDL-C) levels after index LLT, adjusting for baseline characteristics. Results: Overall, 2154 SP and 7179 PP patients met eligibility criteria. Of patients with available laboratory data, only 0.7% (SP) and 0.6% (PP) had Lp(a) test results. In the SP cohort, Lp(a) levels ≥125 nmol/L and ≥175 nmol/L were 26.4% and 17.6%, respectively, and the mean (SD) Lp(a) levels (overall SP cohort 90.4 [97.9] nmol/L) were highest in Black patients (123.4 [117.4]; p<0.001). Statin monotherapy was the most frequently prescribed LLT in SP patients overall (89.4%). Median (interquartile range [IQR]) persistence of LLTs was 227 (91, 649) days and 33.6% achieved ≥80% proportion of days covered (PDC). Patients with Lp(a) ≥175 nmol/L had 2.1 times greater odds of having elevated LDL-C (≥70 mg/dL) post-LLT than those with Lp(a) <175 nmol/L (p = 0.031). Similar findings were observed in the PP population. Conclusions: Lp(a) screening was rare. Elevated Lp(a) was observed in more than one-quarter of patients receiving LLTs, with the highest mean Lp(a) levels observed in Black patients. Low adherence to LLTs was prevalent and at least half of patients failed to achieve their respective LDL-C target thresholds despite treatment. Finally, high Lp(a) levels were associated with worse LDL-C control.

Real-world disease-modifying therapy pathways from administrative claims data in patients with multiple sclerosis.

BACKGROUND: Over a dozen disease-modifying therapies (DMTs) have been approved for treatment of multiple sclerosis (MS). Treatment guidelines focus on when to initiate, change, and discontinue treatment but provide little guidance on how to select or sequence DMTs. This study assessed sequencing patterns of DMTs in patients with newly diagnosed MS. METHODS: Adults newly diagnosed with MS in the United States were identified from January 2007 to October 2017 using IBM MarketScan database. Patients had ≥12 months of continuous enrollment prior to diagnosis and ≥ 2 years of follow-up. Treatment pathways consisting of up to 3 DMT courses were reported, and each treatment course ended with discontinuation, switch, or end of follow-up. RESULTS: In total, 14,627 MS patients were treated with DMTs and had ≥2 years of follow-up. More than 400 DMT treatment pathways were observed. Glatiramer acetate was the most common DMT; 40% of patients initiated this treatment. Among these, 51.3% had 2 DMT courses during follow-up and 26.5% had 3 DMT courses. Approximately 70% of patients switched or discontinued their initial DMT, and rates of switch and discontinuation differed by initial DMT. Injectable DMTs were used most commonly over the study period (87.5% as first course to 66.6% as third course). Oral DMTs were more common as second or third treatment courses (29.9% and 31.8%, respectively). CONCLUSIONS: A wide variety in treatment patterns were observed among patients newly diagnosed with MS. Further examination of DMT prescribing practices is needed to understand the reasons behind treatment discontinuation and treatment cycling.

Retrospective Claims Analysis of Treatment Patterns, Relapse, Utilization, and Cost Among Patients with Multiple Sclerosis Initiating Second-Line Disease-Modifying Therapy.

BACKGROUND: Real-world studies of disease-modifying therapies (DMTs) in multiple sclerosis (MS) have reported suboptimal adherence. OBJECTIVE: We aimed to describe treatment patterns, relapses, healthcare resource utilization, and costs in MS patients experiencing their first observed DMT switch. METHODS: In this retrospective, claims database study, adult patients were selected if they had an MS diagnosis and DMT claim during the study period (1 January 2009-31 March 2019). Patients who switched to a new DMT between 1 January 2010 and 31 March 2018 were included. Adherence, persistence, relapses, and all-cause and MS-related healthcare utilization and costs were reported pre- and post-index. RESULTS: In total, 1554 MS patients were identified; the mean age was 46 years and most (74%) were female. The majority of patients switched from an injectable DMT (n = 1116; 71.8%), and patients generally switched to an oral DMT (n = 878; 57%). Among patients who switched DMTs, 46.0% (n = 715) were nonadherent, 42% (n = 645) were nonpersistent, and 21.5% (n = 334) relapsed in the 12 months post-switch. An increase in all-cause and MS-related healthcare costs was observed pre- to post-index for all patients. Cost drivers included outpatient visit costs and pharmacy prescriptions. Compared with patients who switched to an injectable DMT, those who switched to an oral DMT had significantly higher persistence and adherence. No significant difference was observed in post-index relapse or all-cause and MS-related total cost of care. CONCLUSION: Low adherence and poor persistence remain following an initial DMT switch; however, patients who switched to oral DMTs had higher persistence and adherence.

Multiple sclerosis (MS) is a disabling disease that is treated with disease-modifying therapies (DMTs). Little is known about how patients with MS take their medication, how disease progression may change with treatment, or what the impact of switching to a new DMT is on the cost of care. In an analysis of commercially insured individuals, patients with MS were examined before and after switching to a new DMT. Results showed that the patients most often switched from an injectable medication to an oral DMT; however, a large proportion of patients did not take the prescription as directed by their physician. Additionally, a large proportion of patients did not stay on their new therapy. Nearly one-third of patients experienced an MS relapse after they switched to a new treatment, and healthcare costs increased following the treatment switch. A higher proportion of patients switching to an oral DMT took their medication as prescribed by their physicians, stayed on therapy, and incurred smaller increases in cost compared with patients switching to injectable medications. Despite such improvements, additional treatments are needed for patients with MS.

A Study Comparing Patient and Clinician Perspectives of Treatments for Multiple Sclerosis via Group Concept Mapping.

BACKGROUND: Clinicians treating multiple sclerosis (MS) should consider patient preferences when making treatment decisions. An online mixed-methods approach to elicit patient-centered concepts, group concept mapping (GCM), was used to generate statements reflecting the patient experience in relapsing-remitting MS and identify the most important patient-centered outcomes from patient and clinician perspectives. PATIENTS AND METHODS: Twenty patients and 12 MS specialists in the United States provided statements describing what an ideal treatment would do to improve symptoms and daily functioning. Statements were sorted by participants into meaningful domains and rated on importance on an 11-point scale. RESULTS: Sixty-four unique statements supporting 6 domains of clustered concepts were generated. Patient and clinician ratings of importance were highly correlated (r=0.82); however, patients rated the domains of Activities of Daily Living, Prevent & Cure, and Address Symptoms as highest in importance, whereas clinicians rated Prevent & Cure, Safe & Effective, and Activities of Daily Living as highest in importance. Statements rated above the domain mean by both patients and clinicians included "Improve cognitive function" and "Improve motor function" in the Activities of Daily Living domain and "Help with memory issues" and "Help preserve cognition" in the Address Symptoms domain. The statement "Improve short term memory" was 1 of 3 statements rated above the domain mean by patients but below the domain mean by clinicians. CONCLUSION: High levels of agreement of concept importance were found between patients and MS specialists, although certain domains and statements were rated more highly by one group. Overall, concepts such as cognitive function, physical and emotional functioning, and activities of daily living were perceived as having great importance for treatment outcomes versus symptom-focused outcomes like gait or tingling sensations. This comprehensive concept model for the MS patient experience can be used for further development of patient-centered outcome measures in MS treatment.

Evaluating Treatment Patterns, Relapses, Healthcare Resource Utilization, and Costs Associated with Disease-Modifying Treatments for Multiple Sclerosis in DMT-Naïve Patients.

PURPOSE: Early diagnosis and treatment of multiple sclerosis (MS) with disease-modifying therapy (DMT) can reduce relapse number and severity, which has cost implications. We describe treatment patterns, healthcare utilization, and cost among MS patients newly initiating DMTs (index). PATIENTS AND METHODS: DMT-naïve adults with 12 months' continuous enrollment pre- and post-index and ≥2 MS claims (2009‒2018) were identified from the Optum Clinformatics Data Mart database. Treatment adherence and persistence were measured as time on index DMT. Relapses were identified using a validated claims-based algorithm. All-cause and MS-related healthcare expenditures and utilization were captured pre- and post-index. Outcomes were stratified by route of administration. Multivariate analyses assessed differences in outcomes and costs. RESULTS: The analysis included 5906 MS patients (mean age, 46.6 years). The majority initiated injectable (63.5%) followed by oral (28.8%) and infusion (7.7%) DMTs. Post-index, 45.3% of patients were nonadherent and 39.4% were nonpersistent. Relapse rates decreased from pre- to post-index (oral: 24.3%‒16.1%; injectable: 25.0%‒17.1%; infusion: 29.3%‒15.5%). Post-index mean (SD) all-cause total costs were lowest with oral ($70,970 [$36,681]) vs injectable ($82,521 [$58,569]) and infusion ($80,871 [$49,627]) DMTs. MS-related total costs were lowest with oral ($65,149 [$65,133]) vs injectable ($76,197 [$60,204]) and infusion ($72,703 [$47,287]) DMTs. Multivariate analysis showed no differences between oral and injectable DMTs in adherence, persistence, or relapse rate; however, oral DMTs had significantly lower all-cause and MS-related costs. CONCLUSION: With similar outcomes across DMT administration routes, initiating the least costly DMT may be warranted for many patients. In newly treated MS patients, the need exists to improve adherence and persistence.

Productivity Loss and Associated Costs Among Employed Patients Receiving Disease-Modifying Treatment for Multiple Sclerosis.

OBJECTIVES: The aim of this study was to examine the indirect burden of employed multiple sclerosis (MS) patients initiating disease-modifying therapies (DMTs) in the US. METHODS: DMT-treated MS patients (DMT users) and direct-matched controls without MS (1:3) were captured using the IBM MarketScan Commercial Claims and Encounters Database and the Health and Productivity Management Database between 1 January 2009 and 1 January 2017. DMT users were also stratified by route of administration. Time loss and costs from absenteeism, short-term disability, and long-term disability were assessed for DMT users and matched controls. RESULTS: A total of 3022 DMT users were matched to 9066 controls. Compared with injectable DMT users, oral DMT users took twice as long to initiate therapy but had numerically lower absenteeism costs and significantly lower long-term disability costs in the first year after DMT initiation. The mean (standard deviation) indirect costs of absenteeism, short-term disability, and long-term disability were US$6474 (US$6779), US$2368 (US$5777), and US$280 (US$2578), respectively, for DMT users and US$4468 (US$3814), US$328 (US$1950), and US$36 (US$938), respectively, for controls in the first year (all p < 0.001). CONCLUSIONS: Employed DMT users in the US incurred incremental increased indirect burden ($2007 in absenteeism, $2040 in short-term disability, and $244 in long-term disability) compared with matched controls. Despite evidence of delays in treatment initiation, oral DMT users had evidence of reduced work loss compared with injectable users, suggesting that open access to all treatment options may reduce the indirect burden of MS. Additional research into the impact of route of administration on the burden of long-term disability among MS patients is needed.

Treatment Patterns and Relapses Among Newly Treated Multiple Sclerosis Patients From a Retrospective Claims Analysis.

PURPOSE: Although all disease-modifying therapies (DMTs) reduce risk of relapse in multiple sclerosis (MS), many factors, including route of administration, influence selection of first-line DMT. Knowledge of real-world treatment patterns and effectiveness in reducing relapses across DMTs is important to understanding factors influencing this choice. This study sought to describe treatment patterns and relapses among newly treated adults with MS and by DMT route of administration (oral, injectable, and infusion). METHODS: IBM MarketScan research databases were used to identify MS adults newly initiating DMTs (index event) from January 1, 2011-April 1, 2016, who had 12 months of continuous preindex and postindex medical and pharmacy benefits. Newly treated patients were those with ≥2 nondiagnostic claims with an International Classification of Diseases, Ninth Revision, Clinical Modification (340) or Tenth Revision, Clinical Modification (G35) code and no DMT prescription claims in the 12 months' preindex. Persistence and adherence were measured from index until the earliest of ≥60 days without DMT, switching DMTs, or end of follow-up. Relapses were defined using a validated claims-based algorithm and measured in the 12-month preindex and postindex periods. Regression analysis adjusting for patient characteristics and prior relapses was used to determine the association between DMT route of administration and odds of 12-month persistence, odds of postindex relapse, and number of postindex relapses. FINDINGS: Of 9378 newly treated MS patients meeting inclusion criteria; average age was 46.7 years, and 73.3% were female. Most patients initiated an injectable (65.5%) or oral (26.1%) DMT. Relapses decreased markedly from preindex to postindex (32.9%-24.0%), which was highest among oral users (35.8%-21.6%). Patients with no (vs ≥3) relapses preindex were more likely to be relapse free postindex (81.6% vs 31.4%). Nonpersistence (39.1% overall) was lowest among oral users (33.4%) and higher among those with versus without a postindex relapse (50.6% vs 35.5%). Patients initiating oral versus injectable agents were more likely to be persistent at 12 months (odds ratio [OR], 1.45; p < 0.0001) and less likely to relapse (OR, 0.75; p < 0.0001) postindex. Switches were uncommon (~10%) across cohorts. Preindex relapses were associated with increased odds of postindex relapses (OR, 1.73; p < 0.0001) but not with odds of persistence at 12 months. IMPLICATIONS: The 12-month nonpersistence rate was high among all MS patients but lower among oral users. Oral users were also less likely to relapse postindex. Despite the effectiveness of DMTs in reducing relapses, the low persistence, lack of switching to a new DMT, and continued relapses highlight an unmet need in the MS treatment landscape.

Causal inference and adjustment for reference-arm risk in indirect treatment comparison meta-analysis.

Aim: To illustrate that bias associated with indirect treatment comparison and network meta-analyses can be reduced by adjusting for outcomes on common reference arms. Materials & methods: Approaches to adjusting for reference-arm effects are presented within a causal inference framework. Bayesian and Frequentist approaches are applied to three real data examples. Results: Reference-arm adjustment can significantly impact estimated treatment differences, improve model fit and align indirectly estimated treatment effects with those observed in randomized trials. Reference-arm adjustment can possibly reverse the direction of estimated treatment effects. Conclusion: Accumulating theoretical and empirical evidence underscores the importance of adjusting for reference-arm outcomes in indirect treatment comparison and network meta-analyses to make full use of data and reduce the risk of bias in estimated treatments effects.

Treatment Patterns Among Patients with Multiple Sclerosis Initiating Second-Line Disease-Modifying Therapy.

OBJECTIVE: Disease-modifying therapies (DMTs) can reduce multiple sclerosis (MS) relapse rates; however, effectiveness of treatments may vary. It is important to understand real-world treatment patterns in the context of MS relapses. We describe MS relapses related to treatment patterns among patients who switch treatment after their first DMT. METHODS: IBM MarketScan research databases were used to identify adult patients with MS who switched DMTs (index-first switch) after being newly treated with a DMT from January 2009 through March 2017, with 12 months of continuous enrollment pre- and post-index. Non-persistence was defined as discontinuing (at least 60 days without DMT) or switching DMTs. MS relapses were defined using a validated claims-based algorithm. Multivariable analysis was used to examine odds of 12-month persistence, odds of post-index relapse, and number of relapses. RESULTS: In total, 4121 patients with MS met all inclusion criteria (mean age 46.4 years; female 76.2%). Overall, 49.6% switched to an oral DMT, 36.5% to an injectable DMT, and 13.9% to an infusion DMT. Switching DMTs resulted in a 32.4% reduction in relapses between pre- and post-index. Only 54.6% of patients were persistent throughout the first year. Patients who switched to oral DMTs had 95% higher adjusted odds of persistence and 18% lower adjusted odds of a post-index period relapse than patients who switched to injectable DMTs. The number of baseline relapses was not associated with persistence but with 68% higher odds of a post-index relapse, with each additional baseline relapse associated with a 44% increase in number of post-index relapses. CONCLUSIONS: Among patients with MS who switched DMTs, persistence was consistently low regardless of treatment. Although persistence with oral DMTs was slightly higher than with injectable DMTs, overall results indicate poor persistence to second-line therapy and highlight the need to improve long-term persistence with DMTs.

Comparative safety and efficacy of ozanimod versus fingolimod for relapsing multiple sclerosis.

Aim: Ozanimod and fingolimod are sphingosine 1-phosphate receptor-modulating therapies for relapsing multiple sclerosis. Patients & methods: Comparative effectiveness was assessed by matching adjusted indirect comparisons of safety and efficacy trial outcomes at first-dose cardiac monitoring, 1 year and 2 years. Results: After adjustment, baseline characteristics were similar. Ozanimod was associated with a lower risk of extended first-dose monitoring, conduction abnormalities including atrioventricular block. One-year risks of any adverse event (AE), mean lymphocyte count reductions and abnormal liver enzymes were lower with ozanimod. Two-year risks of AEs leading to discontinuation, any AEs, herpetic infections, bradycardia and abnormal liver enzymes were lower with ozanimod. Analyses of efficacy outcomes were similar. Conclusion: Ozanimod appears to have a favorable benefit-risk profile versus fingolimod.

Treatment patterns and costs among biologic-naive patients initiating apremilast or biologics for psoriatic arthritis.

Aim: We evaluated treatment patterns and healthcare costs of initiating psoriatic arthritis (PsA) treatment with oral apremilast versus biologics. Methods: Claims data identified biologic-naive adults with PsA who initiated either apremilast or a biologic from 2013 to 2016. Results: Medication adherence was similar at 12 months (76.9 vs 73.4%; p = 0.175) between apremilast (n = 381) and matched biologic (n = 761) patients. Apremilast users had $12,715 lower total costs per-patient-per-month (p < 0.001), largely due to outpatient pharmacy and medical costs. Conclusion: Commercially insured patients with PsA initiating apremilast had adherence similar to those initiating biologics but lower total healthcare costs.

Real-world US healthcare costs of psoriasis for biologic-naive patients initiating apremilast or biologics.

AIM: Biologics and apremilast have advanced psoriasis management by adding treatment options. This study evaluated persistence, adherence and healthcare costs among biologic-naive patients receiving apremilast or biologics. METHODS: Administrative claims data for adults starting apremilast or biologics from 1 January 2013 to 30 June 2016 were matched based on demographics. RESULTS: Apremilast (n = 703) and biologics (n = 1378) had similar baseline characteristics. 12-month persistence and adherence rates were similar. Adjusted total healthcare costs were lower with apremilast versus biologics (p < 0.001) due to lower total outpatient pharmacy costs (p < 0.001). CONCLUSION: Real-world apremilast users had similar adherence and lower total healthcare costs versus biologic users. Apremilast's cost advantage was evident regardless of whether the patients were persistent or nonpersistent, or switched or did not switch treatments.

Impact of enhanced external counterpulsation on Canadian Cardiovascular Society angina class in patients with chronic stable angina: a meta-analysis.

STUDY OBJECTIVE: To evaluate the true magnitude of benefit from enhanced external counterpulsation (EECP) by determining the effect of EECP on Canadian Cardiovascular Society (CCS) angina class in patients with chronic stable angina. DESIGN: Meta-analysis of 13 prospective studies that evaluated patients with stable angina and reported adequate data on CCS angina class. PATIENTS: A total of 949 adult patients with stable angina who underwent EECP treatment. MEASUREMENTS AND MAIN RESULTS: A systematic literature search of studies published between 1950 and February 2009 was performed. Studies were included for meta-analysis if they were reported in the English language, included human subjects, had a prospective study design, and reported adequate data on CCS angina class. The EECP treatment consisted of 35 sessions-1 hour/day, 5 days/week, for 7 weeks. Improvement in angina class was reported as the weighted proportion of patients improving by at least one CCS class from before to after EECP treatment. Heterogeneity was assessed by performing subgroup analyses and using the Cochran Q statistic. Publication bias was assessed by inspection of funnel plots and the Egger bias statistic. Among the 13 studies incorporating 949 patients, angina class was reduced by at least one CCS score in 86% of the patients (95% confidence interval 82-90%, Q statistic p=0.008]. Inspection of funnel plots showed some asymmetry, but the Egger bias statistic showed no publication bias (p=0.97). CONCLUSION: The results of our meta-analysis call for further long-term studies to determine the place of EECP therapy in the management of chronic stable angina. Currently, EECP therapy should be considered for patients with stable angina who are refractory to or not suitable for invasive therapy and/or medical management.