Comparison of Disease-Modifying Therapies for the Management of Multiple Sclerosis: Analysis of Healthcare Resource Utilization and Relapse Rates from US Insurance Claims Data.

BACKGROUND: Data on comparative healthcare resource utilization and costs associated with the newer oral disease-modifying therapies (DMTs) for managing relapsing-remitting multiple sclerosis (MS) in routine clinical practice are limited. The purpose of this study was to estimate healthcare resource utilization, costs, and relapse rates in the year after initiating treatment with dimethyl fumarate (DMF), interferon (IFN)-ß, glatiramer acetate (GA), teriflunomide, or fingolimod in routine clinical practice for patients with MS who did not receive a DMT in the previous year. METHODS: Patients initiating DMF, IFNß, GA, teriflunomide, or fingolimod were identified based on claims data from 2012 to 2015 in the Truven MarketScan Commercial Claims Databases (n = 4194). Healthcare resource utilization assessment included the proportion of patients who were hospitalized, or had emergency room (ER) or urgent care (UC) visits. Healthcare costs were estimated for 1 year before and 1 year after DMT initiation. Relapse episodes were identified based on a published claims-based algorithm and clinical input from the research investigators. RESULTS: After DMT initiation, significant reductions in the proportions of patients who were hospitalized or requiring ER/UC visits were observed in all patient cohorts (p < 0.001 and p < 0.05, respectively). Non-prescription medical costs decreased after DMT initiation, with the largest decrease observed in the DMF cohort (US$5761 reduction, p < 0.0001). Reductions in non-prescription medical costs were associated with decreased use of outpatient services and inpatient hospital stays, and have the potential to partially offset DMT costs. CONCLUSIONS: DMT initiation is associated with reductions in healthcare resource utilization and non-prescription medical costs in routine clinical practice.

Comparative Effectiveness Research of Disease-Modifying Therapies for the Management of Multiple Sclerosis: Analysis of a Large Health Insurance Claims Database.

INTRODUCTION: Limited data are available on the real-world effectiveness of newer oral disease-modifying therapies (DMTs) in multiple sclerosis. The purpose of this study was to retrospectively compare the real-world effectiveness of dimethyl fumarate (DMF), fingolimod, teriflunomide, and injectable DMTs in routine clinical practice based on US claims data. METHODS: Patients newly-initiating DMF, interferon beta (IFNß), glatiramer acetate (GA), teriflunomide, or fingolimod in 2013 were identified in the Truven MarketScan Commercial Claims Databases (N = 6372). Relapse episodes were identified based on a published claim-based algorithm and used to determine the annualized relapse rate (ARR) for the year before and after initiating therapy. Poisson and negative binomial regression was used to determine the adjusted incidence rate ratio (IRR) for each therapy relative to DMF. RESULTS: Significant ARR reductions in the year after initiating therapy were reported for DMF and fingolimod (P < 0.0001). Compared with DMF, the adjusted IRR (95% CI) for relapse in the year after initiating therapy was 1.27 (1.10-1.46) for IFNß, 1.34 (1.17-1.53) for GA, 1.23 (1.05-1.45) for teriflunomide, and 1.03 (0.88-1.21) for fingolimod. Results were consistent across subgroup and sensitivity analyses. CONCLUSION: These real-world data suggest DMF and fingolimod have similar effectiveness and demonstrate superior effectiveness to IFNß, GA, and teriflunomide. FUNDING: Biogen, Cambridge, MA, USA.

Quantifying Differences in Health Care Consumption for the Management of Multiple Sclerosis Within Privately and Publicly Insured Health Care Programs.

BACKGROUND: Multiple sclerosis (MS) is a chronic and debilitating disease of the central nervous system that affects more than 570,000 persons in the United States and 2.3 million worldwide. Since most individuals experience initial symptoms between the ages of 20 and 40 years, MS can have a significant effect on health care consumption, quality of life, productivity, and employment over the long-term disease course. Opportunities exist to better understand how benefit design and other nonclinical factors can affect health care delivery and associated costs. OBJECTIVE: To observe and report variances in health care consumed for the treatment of MS in patients enrolled in privately (commercial) and publicly (Medicaid) funded health insurance programs. METHODS: In a retrospective analysis using Havas Gemini's proprietary MS Benchmarks Disease-Modeling Process and IMS LifeLink Health Plan Claims and Longitudinal Prescriptions databases, integrated medical and pharmacy claims data were analyzed to select patients with a diagnosis of MS during the 2012 calendar year. Comorbidities were determined using ICD-9-CM codes present on medical claims. Prescription drug use was evaluated by pharmacy claims and drug-specific billing codes. RESULTS: 19,984 patients with MS were identified-18,269 from commercial payers and 1,715 from Medicaid. Although total annual costs related to the care of MS for the groups reflected a relatively small difference ($31,107 commercial; $33,344 Medicaid), costs associated with specific service categories varied greatly. Pharmacy costs were considerably less in the Medicaid group; however, inpatient and emergency room costs were as much as 5 times higher. Overall use of disease-modifying treatments (DMTs) in the Medicaid group was seen in 32.5% of patients and 52.1% in the commercial patient group. Thus, lower pharmacy costs in the Medicaid group were possibly related to lesser use of DMTs among that group of patients. CONCLUSIONS: This analysis illustrates that notable variances exist in consumption of health care resources between patients enrolled in privately and publicly funded health care programs. These variances may have additional implications relating to outcomes specific to MS. DISCLOSURES: Funding for this study was contributed by Biogen. The preparation, writing, revision, and approval of this manuscript were conducted in collaboration with Pill, who is employed by Havas Gemini. Livingston, Fay, and Wells are employed by and own stock in Biogen. Iyer was employed with Biogen at the time of the study. Study concept and design were contributed by Livingston, Fay, and Iyer, along with Pill and Wells. Livingston, Fay, and Pill collected the data, along with Iyer and Wells. Data interpretation was performed by Livingston, Fay, and Iyer, along with Pill and Wells. The manuscript was written by Livingston, Fay, and Wells, along with Pill and Iyer, and revised by Fay, Wells, and Pill, along with Livingston and Iyer.

Cost-effectiveness analysis of peginterferon beta-1a compared with interferon beta-1a and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis in the United States.

Objective Peginterferon beta-1a 125 mcg, administered subcutaneously (SC) every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved by the US Food and Drug Administration in 2014. This study assesses the cost-effectiveness of peginterferon beta-1a vs interferon beta-1a (44 mcg SC 3 times per week) and glatiramer acetate (20 mg SC once-daily) in the treatment of RRMS from the perspective of a US payer over 10 years. Methods A Markov cohort economic model was developed for this analysis. The model predicts disability progression, occurrence of relapses and other adverse events and translates them into quality-adjusted life years (QALYs) and costs. Natural history data were obtained from the placebo arm of the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database and a large population-based MS survey. Comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (in 2014 US dollars) were sourced from public databases and literature. Clinical and economic outcomes were discounted at 3% per year. Results Over 10 years, peginterferon beta-1a was dominant (i.e., more effective and less costly), with cost-savings of $22,070 and additional 0.06 QALYs when compared with interferon beta-1a 44 mcg and with cost-savings of $19,163 and 0.07 QALYs gained when compared with glatiramer acetate 20 mg. Results were most sensitive to variations in the treatment effect of each DMT, treatment acquisition costs of each DMT and the time horizon. Probabilistic sensitivity analyses indicated that peginterferon beta-1a remains dominant in >90% of 5,000 replications compared with either DMTs. Conclusion This analysis suggests that long-term treatment with peginterferon beta-1a improves clinical outcomes at reduced costs compared with interferon beta-1a 44 mcg and glatiramer acetate 20 mg and should be a valuable addition to managed care formularies for treating patients with RRMS.

Cost-effectiveness of delayed-release dimethyl fumarate for the treatment of relapsing forms of multiple sclerosis in the United States.

OBJECTIVE: To assess the cost-effectiveness of delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF), an effective therapy for relapsing forms of multiple sclerosis (MS), compared with glatiramer acetate and fingolimod, commonly used treatments in the US. METHODS: A Markov model was developed comparing delayed-release DMF to glatiramer acetate and fingolimod using a US payer perspective and 20-year time horizon. A cohort of patients, mean age 38 years, with relapsing-remitting MS and Kurtzke Expanded Disability Status Scale (EDSS) scores between 0-6 entered the model. Efficacy and safety were estimated by mixed-treatment comparison of data from the DEFINE and CONFIRM trials and clinical trials of other disease-modifying therapies. Data from published studies were used to derive resource use, cost, and utility inputs. Key outcomes included costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Alternative scenarios tested in a sensitivity analysis included drug efficacy, EDSS-related or relapse-related costs, alternative perspectives, drug acquisition costs, and utility. RESULTS: Base-case results with a 20-year time horizon indicated that delayed-release DMF increased QALYs +0.450 or +0.359 compared with glatiramer acetate or fingolimod, respectively. Reductions in 20-year costs with delayed-release DMF were -$70,644 compared with once-daily glatiramer acetate and -$32,958 compared with fingolimod. In an analysis comparing delayed-release DMF to three-times-weekly glatiramer acetate and assuming similar efficacy and safety to the once-daily formulation, 20-year costs with delayed-release DMF were increased by $15,806 and cost per QALY gained was $35,142. The differences in costs were most sensitive to acquisition cost and inclusion of informal care costs and productivity losses. The differences in QALYs were most sensitive to the impact of delayed-release DMF on disease progression and the EDSS utility weights. CONCLUSION: Delayed-release DMF is likely to increase QALYs for patients with relapsing forms of MS and be cost-effective compared with fingolimod and glatiramer acetate.

Impact of increasing adherence to disease-modifying therapies on healthcare resource utilization and direct medical and indirect work loss costs for patients with multiple sclerosis.

OBJECTIVES: To estimate the effect of adherence to disease-modifying therapies (DMTs) among patients with multiple sclerosis (MS) on healthcare resource utilization (HRU) and costs, and model the impact of a 10 percentage point increase in adherence on these outcomes. METHODS: Employed patients, 18-64 years old, with ≥2 MS diagnoses and ≥1 DMT claim during January 1, 2002 to September 30, 2012 were identified from a large commercially-insured US claims database. Adherence was measured as proportion of days covered (PDC) during follow-up. Multivariate regression analyses were conducted to estimate the effect of adherence on HRU related to urgent care (i.e., inpatient or emergency room visit), days of work loss, direct medical cost, and indirect work loss costs. Model coefficients were used to evaluate the impact of a 10 percentage point increase in adherence on the outcomes. RESULTS: A total of 1510 patients were included (mean age = 43.4 years, 64% female). Patients with higher adherence had lower HRU, fewer days of work loss, and lower direct and indirect costs. A 10 percentage point increase in adherence significantly decreased the likelihood of an inpatient or emergency room visit by 9-19%, days of work loss by 3-8%, and direct and indirect costs by 3-5%, depending on the follow-up period (all p < 0.01). CONCLUSIONS: Increasing DMT adherence was found to significantly decrease urgent-care HRU, days of work loss, and direct and indirect costs among patients with MS.

Oral absorption kinetics of levetiracetam: the effect of mixing with food or enteral nutrition formulas.

BACKGROUND: Levetiracetam (LEV) is an antiepileptic drug with a favorable pharmacokinetic profile, including negligible protein binding and linear elimination kinetics. Because LEV is likely to be used in populations that include children and the elderly, alternative techniques of administration, such as crushing the tablet and mixing its contents with semisolid food or enteral nutrition formulas (ENFs), may be required in some clinical settings. Although previous studies have suggested that administration with food does not affect the overall absorption of LEV, there is a lack of data regarding concomitant administration with ENFs. OBJECTIVE: The objective of this study was to evaluate the oral absorption of LEV after concomitant administration with food or ENFs. METHODS: This was an unblinded, 3-way crossover study. After an overnight fast, subjects received a single dose of LEV 500 mg administered either as an intact tablet with 120 mL water (control, treatment A) or crushed and mixed with 4 oz applesauce (treatment B) or 120 mL of a common ENF (treatment C). All subjects received each treatment in a randomized sequence; there was a 7-day washout period between treatments. Serial blood samples were obtained over 24 hours for determination of the LEV serum concentration-time profile using gas chromatography with nitrogen phosphorus detection. AUC(0-24), C(max), and T(max) were calculated using noncompartmental methods and analyzed using analysis of variance. RESULTS: Ten healthy adult volunteers (6 men, 4 women) participated in the study (mean [SD] age, 28.9 [6.5] years; mean body weight, 78.6 [12.9] kg). No significant differences were noted between control and any other study treatment. Mean AUC values were 191.9 (50.2), 165.7 (43.4), and 168.3 (43.9) microg/mL . h for treatments A, B, and C, respectively. Mean T(max) values were 1.08 (0.65), 1.32 (0.75), and 1.62 (0.73) hours, respectively. Mean C(max) values were 14.8 (5.6), 12.1 (2.8), and 10.8 (2.0) microg/mL for the respective treatments. Mean LEV serum concentrations at 12 hours after dosing were similar for all study treatments (3.9, 4.1, and 4.0 microg/mL). The long-term stability of LEV in the various combinations was not assessed. CONCLUSIONS: In these healthy volunteers, the overall rate and extent of absorption of oral LEV were not significantly impaired after crushing and mixing of the tablet with either a food vehicle or a typical ENF product. The data suggest that peak serum concentrations of LEV may be slightly reduced after mixing with ENFs, although the difference was not significant compared with control values.