Outcomes and Health Care Service Use in Adults 50 Years or Older With and Without Multiple Sclerosis: A 6-Year Observational Analysis.

BACKGROUND: Multiple sclerosis (MS) typically presents in young adulthood. Recent data show the highest prevalence of MS in people aged 55 to 64 years; however, there are limited studies of this population. METHODS: Administrative US claims data from IBM-Truven MarketScan commercial and Medicare databases (2011-2017) were analyzed. People with MS 50 years or older were assigned to the aging MS cohort (n = 10,746). The matched controls were people 50 years or older without MS (n = 10,746). Multivariable models compared outcomes between groups. RESULTS: Infections were more frequent in the aging MS cohort vs matched controls (61% vs 45%; P < .0001); urinary tract, acute upper respiratory tract, and herpes zoster were the most frequent infection types. Malignancy rates were 20% for both groups (P = .8167); skin, breast, and prostate malignancies were the most frequent types. Skilled nursing facilities (aging MS cohort, 12%; matched controls, 3%; P < .0001) and MRI (aging MS cohort, 87%; matched controls, 37%; P < .0001) were used more frequently in the aging MS cohort; brain and spine were the most frequent types of MRI in the aging MS cohort. Time to first cane/walker or wheelchair use was shorter in the aging MS cohort (cane/walker use: HR, 2.1; 95% CI, 1.9-2.3; P < .0001; wheelchair use: HR, 6.9; 95% CI, 6.0-8.1; P < .0001). CONCLUSIONS: In people 50 years or older, measures typically associated with worse health primarily resulted from having MS rather than being a consequence of aging alone.

Impact of adherence to disease modifying therapies on long-term clinical and economic outcomes in multiple sclerosis: A claims analysis of real-world data.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurodegenerative inflammatory disease that requires long-term commitment to treatment for optimal outcomes. A variety of disease-modifying therapies (DMTs) are now available that reduce relapses and delay disease progression in people with MS. However, adherence remains a significant issue, with a variety of mental, physical, and emotional factors contributing to non-adherence. In a large number of studies, non-adherence has been associated with worse clinical outcomes (relapses and disease severity), a higher economic burden, and loss of work productivity. However, many of these studies were short-term (1-2 years) or cross-sectional studies; thus, more data are needed on the long-term clinical and economic impacts of DMT non-adherence. The objective of this study was to determine the longer-term impact of adherence to DMTs on disease activity and healthcare resource utilization (HCRU) in people with MS. The study hypothesis was that non-adherence to DMTs would be associated long-term with worse clinical outcomes and a higher economic burden. METHODS: A retrospective administrative claims analysis of the US MarketScan® Commercial database (2011-2017) in individuals (18-65 years) with MS (based on International Classification of Disease coding) was conducted. Adherence was classified by proportion of days covered (PDC) ≥0.8 and non-adherence by PDC <0.8; sensitivity analyses helped further categorize as moderately (PDC ≥0.6-<0.8) or highly (PDC <0.6) non-adherent. Cohorts were matched using propensity score matching. Time to first relapse, annualized relapse rate (ARR), time to use of assistive devices (cane/walker or wheelchair), and annual HCRU (inpatient, emergency room [ER], outpatient, and MRI visits and costs) were compared between cohorts. RESULTS: 10,248 MS cases were identified; 58% met adherence criteria, and 42% met non-adherence criteria. Mean follow-up from diagnosis or first DMT claim was 5.3 years. Adherent individuals had a longer time to first relapse (hazard ratio [HR] 0.83; 95% confidence interval [CI]: 0.77-0.90; p<0.0001), a lower ARR (0.13 vs. 0.18, respectively; rate ratio [RR] 0.75 [95% CI: 0.71-0.79]; p<0.0001), and longer lag times to cane/walker use (HR 0.79 [95% CI: 0.66-0.94]; p=0.0067) and wheelchair use (HR 0.68 [95% CI: 0.55-0.83]; p=0.0002) than non-adherent individuals. Adherent individuals had fewer annual inpatient and ER visits and lower total costs than those who were non-adherent (p<0.0001). Sensitivity analyses showed that differences in disease activity and HCRU were generally more pronounced between matched adherent and highly non-adherent pairs than between matched adherent and moderately non-adherent pairs. CONCLUSION: Significant differences in MS disease activity and HCRU were observed based on adherence to DMTs. Our study underscores the negative impact of non-adherence to DMTs on long-term clinical and economic outcomes in MS.

Neuroimaging to monitor worsening of multiple sclerosis: advances supported by the grant for multiple sclerosis innovation.

Key unmet needs in multiple sclerosis (MS) include detection of early pathology, disability worsening independent of relapses, and accurate monitoring of treatment response. Collaborative approaches to address these unmet needs have been driven in part by industry-academic networks and initiatives such as the Grant for Multiple Sclerosis Innovation (GMSI) and Multiple Sclerosis Leadership and Innovation Network (MS-LINK™) programs. We review the application of recent advances, supported by the GMSI and MS-LINK™ programs, in neuroimaging technology to quantify pathology related to central pathology and disease worsening, and potential for their translation into clinical practice/trials. GMSI-supported advances in neuroimaging methods and biomarkers include developments in magnetic resonance imaging, positron emission tomography, ocular imaging, and machine learning. However, longitudinal studies are required to facilitate translation of these measures to the clinic and to justify their inclusion as endpoints in clinical trials of new therapeutics for MS. Novel neuroimaging measures and other biomarkers, combined with artificial intelligence, may enable accurate prediction and monitoring of MS worsening in the clinic, and may also be used as endpoints in clinical trials of new therapies for MS targeting relapse-independent disease pathology.

Implementing Shared Decision-Making for Multiple Sclerosis: The MS-SUPPORT Tool.

BACKGROUND: Disease modifying therapies (DMTs) offer opportunities to improve the course of multiple sclerosis (MS), but decisions about treatment are difficult. People with multiple sclerosis (pwMS) want more involvement in decisions about DMTs, but new approaches are needed to support shared decision-making (SDM) because of the number of treatment options and the range of outcomes affected by treatment. We designed a patient-centered tool, MS-SUPPORT, to facilitate SDM for pwMS. We sought to evaluate the feasibility and impact of MS-SUPPORT on decisions about disease modifying treatments (DMTs), SDM processes, and quality-of-life. METHODS: This multisite randomized controlled trial compared the SDM intervention (MS-SUPPORT) to control (usual care) over a 12-month period. English-speaking adults with relapsing MS were eligible if they had an upcoming MS appointment and an email address. To evaluate clinician perspectives, participants' MS clinicians were invited to participate. Patients were referred between November 11, 2019 and October 23, 2020 by their MS clinician or a patient advocacy organization (the Multiple Sclerosis Association of America). MS-SUPPORT is an online, interactive, evidence-based decision aid that was co-created with pwMS. It clarifies patient treatment goals and values and provides tailored information about MS, DMTs, and adherence. Viewed by patients before their clinic appointment, MS-SUPPORT generates a personalized summary of the patient's treatment goals and preferences, adherence, DMT use, and clinical situation to share with their MS clinician. Outcomes (DMT utilization, adherence, quality-of-life, and SDM) were assessed at enrollment, post-MS-SUPPORT, post-appointment, and quarterly for 1 year. RESULTS: Participants included 501 adults with MS from across the USA (84.6% female, 83% white) and 34 of their MS clinicians (47% neurologists, 41% Nurse Practitioners, 12% Physician Assistants). Among the 203 patients who completed MS-SUPPORT, most (88.2%) reported they would recommend it to others and that it helped them talk to their doctor (85.2%), understand their options (82.3%) and the importance of taking DMTs as prescribed (82.3%). Among non-users of DMTs at baseline, the probability ratio of current DMT use consistently trended higher over one-year follow-up in the MS-SUPPORT group (1.30 [0.86-1.96]), as did the cumulative probability of starting a DMT within 6-months, with shorter time-to-start (46 vs 90 days, p=0.24). Among the 222 responses from 34 participating clinicians, more clinicians in the MS-SUPPORT group (vs control) trended towards recommending their patient start a DMT (9 of 108 (8%) vs 5 of 109 (5%), respectively, p=0.26). Adherence (no missed doses) to daily-dosed DMTs was higher in the MS-SUPPORT group (81.25% vs 56.41%, p=.026). Fewer patients forgot their doses (p=.046). The MS-SUPPORT group (vs control) reported 1.7 fewer days/month of poor mental health (p=0.02). CONCLUSIONS: MS-SUPPORT was strongly endorsed by patients and is feasible to use in clinical settings. MS-SUPPORT increased the short-term probability of taking and adhering to a DMT, and improved long-term mental health. Study limitations include selection bias, response bias, social desirability bias, and recall bias. Exploring approaches to reinforcement and monitoring its implementation in real-world settings should provide further insights into the value and utility of this new SDM tool.

Perceptions and Preferences Regarding Multiple Sclerosis Research Among Racial and Ethnic Groups.

BACKGROUND: For unclear reasons, minorities have been historically underrepresented in multiple sclerosis (MS) clinical trials. We hypothesized that different perceptions and preferences about research participation among racial and ethnic groups contribute to this imbalance. METHODS: Members of the MS Minority Research Engagement Partnership Network developed a Web-based survey in English and Spanish on research impressions, concerns, and preferences regarding study attributes among people with MS. Invitations to take the survey were distributed by network members and partner organizations. RESULTS: We included 2599 participants with MS (2111 White, 215 African American; 188 Hispanic). Consistently disliked study attributes included potential harms to health and confusing study information. Compared with White and non-Hispanic participants, respectively, African American (odds ratio [OR] = 2.05, P ≤ .001) and Hispanic (OR = 1.79, P = .003) participants were more concerned about being used by the research team. Hispanic participants were more concerned about research participation carrying risks to their legal status (OR = 1.70, P = .001). Hispanic (OR = 3.18, P ≤ .001) and African American (OR = 5.51, P ≤ .001) participants were more likely to prefer for the study to benefit their own racial/ethnic group. A top concern across all groups was not being fully informed about the research. CONCLUSIONS: We found strong support for research across racial and ethnic groups; however, minority groups have specific concerns regarding mistrust, receiving poor-quality care, unemployment, health insurance, and legal status. Investigators wanting to recruit a diverse study population are advised to show how they have addressed these concerns and to communicate how the research will advance the science and literature and result in better care and/or other benefits to underrepresented communities.

Comparative effectiveness of dimethyl fumarate versus fingolimod and teriflunomide among MS patients switching from first-generation platform therapies in the US.

BACKGROUND: Previous real-world comparative research of MS disease modifying therapies (DMTs) in the overall population has suggested dimethyl fumarate (DMF) to be comparable to fingolimod (FTY) and more efficacious than teriflunomide (TERI) in reducing relapses. However, there is limited comparative evidence in patients switching from platform DMTs in the US. The objective of the study was to compare the annualized relapse rate (ARR) and risk of relapse in MS patients who have switched from a platform therapy to DMF, FTY, or TERI. METHODS: MS patients (18-65 years old) initiating an oral DMT from June 2013 to March 2015 were identified from the Truven MarketScan® Commercial Claims Database. The index date was the date of first oral DMT fill. Patients were required to have: continuous enrollment in the database for 12 months pre-index date and ≥3 months post-index date; ≥1 MS diagnosis over the pre-index period; discontinuation of a platform DMT with no evidence of oral or infusion DMTs over the pre-index period; and adherence to the index drug for ≥90 days. DMF patients were propensity-score matched (PSM) 3:1 to FTY and to TERI based on age, gender, region, a claims-based MS severity measure, ARR, and number of hospitalizations over the pre-index period. Patients were censored when they dropped out of the database or at the end of the study period (March 31, 2016). Post-index relapses were annualized. RESULTS: The database included 20,311 oral DMT users. After applying the study criteria, the PSM yielded 1602:534 switch patients for the DMF-FTY matched cohort. DMF-FTY patients were well-matched on all covariates: age (mean = 44 for both), gender (28% vs. 26% male, respectively), MS severity measure (0.99 vs. 1.08), and baseline ARR (0.40 vs. 0.44). PSM yielded 833:279 switch patients for the DMF-TERI match. DMF-TERI patients were well-matched on all covariates: age (mean = 50), gender (24% vs. 25% male), MS severity measure (0.86 vs. 0.99), and baseline ARR (0.23 vs. 0.30). The standardized differences confirmed balance across all covariates for matched cohorts. The matched DMF-FTY cohorts had comparable post-index ARR (Rate Ratio [RR] = 1.07 [95% Cl: 0.861, 1.328]) and risk of relapse (Hazard Ratio [HR ]= 0.996 [95% CI: 0.803, 1.236]). Post-index ARR was significantly lower with DMF in comparison to TERI (RR = 0.667 [0.486, 0.914]). The risk of relapse was also significantly lower when switching to DMF than TERI (HR = 0.679 [0.503, 0.917]). CONCLUSION: In this analysis, the effectiveness profiles for those oral DMT users specifically switching from platform therapies are consistent with findings from previous research conducted among all oral DMT users, regardless of prior therapy.

A Novel Tool to Improve Shared Decision Making and Adherence in Multiple Sclerosis: Development and Preliminary Testing.

Background. Most people with multiple sclerosis (MS) want to be involved in medical decision making about disease-modifying therapies (DMTs), but new approaches are needed to overcome barriers to participation. Objectives. We sought to develop a shared decision-making (SDM) tool for MS DMTs, evaluate patient and provider responses to the tool, and address challenges encountered during development to guide a future trial. Methods. We created a patient-centered design process informed by image theory to develop the MS-SUPPORT SDM tool. Development included semistructured interviews and alpha and beta testing with MS patients and providers. Beta testing assessed dissemination and clinical integration strategies, decision-making processes, communication, and adherence. Patients evaluated the tool before and after a clinic visit. Results. MS-SUPPORT combines self-assessment with tailored feedback to help patients identify their treatment goals and preferences, correct misperceptions, frame decisions, and promote adherence. MS-SUPPORT generates a personal summary of their responses that patients can share with their provider to facilitate communication. Alpha testing (14 patients) identified areas needing improvement, resulting in reorganization and shortening of the tool. MS-SUPPORT was highly rated in beta testing (15 patients, 4 providers) on patient-provider communication, patient preparation, adherence, and other endpoints. Dissemination through both patient and provider networks appeared feasible. All patient testers wanted to share the summary report with their provider, but only 60% did. Limitations. Small sample size, no comparison group. Conclusions. The development process resulted in a patient-centered SDM tool for MS that may facilitate patient involvement in decision making, help providers understand their patients' preferences, and improve adherence, though further testing is needed. Beta testing in real-world conditions was critical to prepare the tool for future testing and inform the design of future studies.

Treatment satisfaction significantly improves in patients with multiple sclerosis switching from interferon beta therapy to peginterferon beta-1a every 2 weeks.

OBJECTIVES: Posthoc analysis of treatment satisfaction in patients switching to subcutaneous (SC) peginterferon beta-1a in the ALLOW study. PATIENTS AND METHODS: Patients with relapsing multiple sclerosis treated with intramuscular interferon (IFN) beta-1a or SC IFN beta-1a or beta-1b remained on their current therapy for a 4-week run-in period, followed by a switch to SC peginterferon beta-1a 125 mcg every 2 weeks for 48 weeks. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM), which covers effectiveness, side effects, convenience, and global satisfaction. Patients completed the TSQM at baseline (prior to starting the 4-week run-in period) and 4, 12, 24, 36, and 48 weeks after switching, and scores were analyzed for the overall population and compared to baseline. Patients reported the severity of flu-like symptoms (FLS) at baseline and with each peginterferon beta-1a injection; clinicians evaluated the occurrence of injection-site reactions (ISRs) after the first dose of peginterferon beta-1a and every 12 weeks thereafter. TSQM scores were stratified by the presence of FLS or ISRs during the study period and by prior IFN therapy use. RESULTS: For the overall population (n=194), convenience and global satisfaction scores significantly improved from baseline at all time points, and side effect satisfaction scores significantly improved up to week 36. Convenience scores significantly improved regardless of FLS, ISRs, or prior IFN therapy. Patients without FLS during the study period showed significant improvements in global satisfaction, but not side effect satisfaction, versus those with FLS. Patients switching from SC IFN therapies achieved greater improvements in treatment satisfaction than patients who switched from intramuscular IFN beta-1a. CONCLUSIONS: Switching relapsing multiple sclerosis patients to SC peginterferon beta-1a from other IFN therapies significantly improved treatment satisfaction and convenience.

The cost-effectiveness of disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis.

BACKGROUND: The safety and efficacy of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has been established; however, it is not clear which provides optimal value, given benefit-risk profiles and costs. AIMS: To compare the cost-effectiveness of current DMTs for patients with RRMS in the US. MATERIALS AND METHODS: A Markov model predicting RRMS course following initiation of a DMT was created comparing outcomes (e.g. relapses, disease progression) and costs of natalizumab (NTZ), dimethyl fumarate (DMF), and peginterferon beta-1a (PEG) with fingolimod (FIN), glatiramer acetate (GA, 20 mg daily), and subcutaneous interferon beta-1a (IFN, 44 mcg), respectively, over 10 years. RRMS and secondary-progressive MS (SPMS) EDSS state transitions were predicted in 3-month cycles in which patients were at risk of death, relapse, or discontinuation. Upon DMT discontinuation, natural history progression and relapse rates were applied. Incremental cost-effectiveness ratios (ICERs) were estimated for the cost per relapse avoided, relapse-free years gained, progression avoided, and progression-free years gained. The impact of model parameters on outcomes was evaluated via one-way sensitivity analyses. RESULTS: Costs ranged from $561,177 (NTZ) to $616,251 (GA). NTZ, DMF, and PEG were dominant (less costly and more effective) compared to FIN, GA, and IFN, respectively, for all ICERs. Variability in drug costs and parameters that affected drug cost accrual (e.g. discontinuation rates and the decision to drop out after SPMS conversion) had a considerable impact on ICERs. LIMITATIONS: Several simplifying assumptions were made that may represent potential limitations of this analysis (e.g. a constant treatment effect over time was assumed). CONCLUSIONS: The results from this analysis suggest that the NTZ, DMF, and PEG are cost-effective DMT choices compared to FIN, GA, and IFN, respectively. The actual impact on a particular plan will vary based on drug pricing and other factors affecting drug cost accrual.

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.

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.

Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study.

BACKGROUND: Natalizumab disease-modifying therapy for relapsing-remitting multiple sclerosis (MS) is efficacious in randomized controlled trials. Few studies have estimated the association between real-world natalizumab persistence behavior and relapse-related outcomes. OBJECTIVES: To (a) examine the impact of using natalizumab consistently (i.e., persistent) on relapse-related outcomes as compared with transitioning to inconsistent natalizumab use (i.e., nonpersistent) and (b) examine the impact of other treatment patterns on relapse-related outcomes for those who initiated natalizumab. METHODS: Using the IMS PharMetrics Plus claims database (years 2006-2012), we identified MS subjects who initiated natalizumab (no natalizumab claims in year prior) and had at least 2 years of follow-up. Persistence in annual follow-up periods was defined as no 90-day or greater gap in natalizumab therapy. Relapse was an MS-related hospitalization or outpatient visit with intravenous or oral steroid burst claim within 7 days. Analyses compared observations based on changes in natalizumab persistence and natalizumab nonpersistence status from 1 year to the next (e.g., transitioning from persistent to nonpersistent), estimating differences in mean annual relapses and mean annual relapse-related costs. RESULTS: A total of 2,407 natalizumab initiators had at least 2 years of follow-up, yielding 4,770 year-to-year natalizumab treatment patterns where each subject contributed 1, 2, or 3 year-to-year treatment patterns. In the year prior, 3,187 treatment patterns were persistent; 731 (22.9%) of these transitioned to nonpersistence. The remaining 1,583 treatment patterns were nonpersistent in the year prior; 132 (8.3%) of these transitioned to persistence. Persistent to nonpersistent treatment patterns were associated with a mean relapse-rate increase of 0.23 (95% CI = 0.12, 0.35), and a mean increase in relapse-related costs of $1,346 (95% CI = $97, $2,595). Nonpersistent to persistent treatment patterns were associated with a mean relapse-rate decrease of -0.15 (95% CI = -0.32, 0.017) and a mean decrease in relapse-related costs of -$1,369 (95% CI = -$2,761, $23). CONCLUSIONS: Findings suggest that real-world persistent natalizumab users who become nonpersistent have statistically significant increases in annual relapses and relapse-related costs. Those who transition from nonpersistent to persistent have nonsignificant reductions in relapses and their associated costs.

Burden of multiple sclerosis on direct, indirect costs and quality of life: National US estimates.

BACKGROUND: MS imposes a significant burden on patients, caregivers, employers, and the healthcare system. OBJECTIVE: To comprehensively evaluate the US MS burden using nationally representative data from the Medical Expenditure Panel Survey. METHODS: We identified non-institutionalized patients aged ≥18 with MS (ICD-9 code 340) from 1998 to 2009 and compared them to individuals without an MS diagnosis (non-MS) during the interview year. The cohorts were compared using multivariate regression on direct costs, indirect costs (measured in terms of employment status, annual wages, and workdays missed), and health-related quality of life (HRQoL; measured using Short Form 12, SF-6 Dimensions, and quality-adjusted life years [QALYs]). RESULTS: MS prevalence was 572,312 (95% CI: 397,004, 747,619). Annual direct costs were $24,327 higher for the MS population (n=526) vs. the non-MS population (n=270,345) (95% CI: $22,320, $26,333). MS patients had an adjusted 3.3-fold (95% CI: 2.4, 4.5) increase in the odds of not being employed vs. non-MS individuals and a 4.4-fold higher adjusted number of days in bed (95% CI 2.97, 6.45). On average, MS patients lost 10.04 QALYs vs. non-MS cohort. CONCLUSIONS: MS was associated with higher healthcare costs across all components, reduced productivity due to unemployment and days spent in bed, and lower HRQoL.