Disease-modifying Therapies Treatment Research Articles

Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments.

Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) are lacking. To compare the treatment effect of OCR vs six DMTs' (IFN β-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data. Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to build 1:1 propensity score-matched (PSM) cohorts controlling for seven baseline covariates, including brain imaging activity. Efficacy outcomes were time to first relapse and time to 24-week confirmed disability progression over 5.5years of follow-up. Intention-to-treat analysis using all outcome data irrespective of treatment switch was applied. The analyses included 611 OPERA patients and 7141 NTD patients. We built 12 paired-matched cohorts (six for each outcome, two for each DMT) to compare efficacy of OCR in OPERA with each DMT treatment pathway in NTD. Post-matching, baseline covariates and PS were well balanced (standardized mean difference <.2 for all cohorts). Over 5.5years, patients treated with OCR showed a statistically significant reduction in the risk of relapse (hazard ratios [HRs] .30 to .54) and disability progression (HRs .51 to .67) compared with all index therapies and their treatment switching pathways in NTD. Treatment switch and/or discontinuation occurred frequently in NTD cohorts. OCR demonstrates superiority in controlling relapses and disability progression in RMS compared with real-world treatment pathways over a 5.5-year period. These analyses suggest that high-efficacy DMTs and high treatment persistence are critical to achieve greatest clinical benefit in RMS. OPERA I (NCT01247324), OPERA II (NCT01412333).

Impact of previous treatment history and B-cell depletion treatment duration on infection risk in relapsing-remitting multiple sclerosis: a nationwide cohort study

BackgroundB-cell depletion displays striking effectiveness in relapsing-remitting multiple sclerosis (RRMS), but is also associated with increased infection risk. To what degree previous treatment history, disease-modifying therapy (DMT) switching pattern and...

Real-world persistence of multiple sclerosis disease-modifying therapies.

Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real-world rates of persistence on disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation. Treatment data on 4366 consecutive people with relapse-onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan-Meier survival analyses were used to express DMT persistence. In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1-4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate. Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS.

Disparities in DMT treatment: Demographic and neurocognitive differences between MS patients currently treated versus not treated with disease-modifying therapies

BackgroundCurrent treatment guidelines recommend consideration of disease-modifying therapy (DMT) for all multiple sclerosis (MS) patients, but barriers to access have begun to be identified. In particular, prior studies have found that people with higher education have better access to DMTs, perhaps explained by the association of higher education with higher income. And while the majority of people with MS are women, being male is also associated with higher income. These factors argue for the need to better understand whether there are differences in DMT uptake based on sex and education. Finally, in addition to well-documented benefits of DMTs for slowing disease progression, there is growing evidence to suggest benefits of DMTs for cognitive functioning. ObjectiveDetermine whether rates of DMT treatment differ based on education and sex. Secondarily, we investigate whether neurocognitive test performance differs in treated versus not treated groups. MethodsIn cross-sectional data, mixed effects linear regression evaluated differences in education and sex of those treated versus not treated with DMTs. Models included the following predictors: age, disease duration, MS subtype, sex/education, disability, atrophy, and T2 lesion volume. Propensity score weights were extracted to obtain unbiased estimates of the relationship between DMT status and each outcome of interest. The same models evaluated performance differences between groups on an iPad-based processing speed test (PST) and manual dexterity test (MDT). ResultsControlling for covariates, individuals with less education (OR=1.09, 95 % CI=[1.03, 1.14], p = 0.003) and women (OR=0.80, 95 % CI=[0.72, 0.90], p < 0.001) were less likely to be currently treated with DMTs. Small effect size association was shown for DMT treatment with better performance on PST (beta=0.09, CI=[0.06, 0.13], p < 0.001) and MDT (beta=0.05, CI=[0.01,0.08], p = 0.011). ConclusionsWomen and people with lower education had a lower likelihood of being currently treated with DMTs. After controlling for all relevant variables, an independent (small) association of DMT treatment to better performance on tests of processing speed and fine motor dexterity was found. Reasons for disparities remain to be investigated in future work, and may include employment status, health insurance coverage, or sex differences in risk tolerance.

Correlates and trajectories of relapses in relapsing–remitting multiple sclerosis

Background and aimsIn people with relapsing–remitting multiple sclerosis (pwRRMS), data from studies on non-pharmacological factors which may influence relapse risk, other than age, are inconsistent. There is a reduced risk of relapses with increasing age, but little is known about other trajectories in real-world MS care.MethodsWe studied longitudinal questionnaire data from 3885 pwRRMS, covering smoking, comorbidities, disease-modifying therapy (DMT), and patient-reported outcome measures, as well as relapses during the past year. We undertook Rasch analysis, group-based trajectory modelling, and multilevel negative binomial regression.ResultsThe regression cohort of 6285 data sets from pwRRMS over time showed that being a current smoker was associated with 43.9% greater relapse risk; having 3 or more comorbidities increased risk and increasing age reduced risk. Those diagnosed within the last 2 years showed two distinct trajectories, both reducing in relapse frequency but 25.8% started with a higher rate and took 4 years to reduce to the rate of the second group. In the cohort with at least three data points completed, there were three groups: 73.7% followed a low stable relapse rate, 21.6% started from a higher rate and decreased, and 4.7% had an increasing then decreasing pattern. These different trajectory groups showed significant differences in fatigue, neuropathic pain, disability, health status, quality of life, self-efficacy, and DMT use.ConclusionsThese results provide additional evidence for supporting pwRRMS to stop smoking and underline the importance of timely DMT decisions and treatment initiation soon after diagnosis with RRMS.

Treatment Patterns by Race and Ethnicity in Newly Diagnosed Persons with Multiple Sclerosis.

Non-Hispanic Black and Hispanic persons with MS (pwMS) are more likely to experience rapid disease progression and severe disability than non-Hispanic White pwMS; however, it is unknown how the initiation of high-efficacy disease-modifying therapies (DMTs) differs by race/ethnicity. This real-world study describes DMT treatment patterns in newly diagnosed pwMS in the United States (US) overall and by race/ethnicity. This retrospective analysis used the US Optum Market Clarity claims/electronic health records database (January 2015-September 2020). pwMS who were first diagnosed in 2016 or later and initiated any DMT in the two years following diagnosis were included. Continuous enrollment in the claims data for ≥ 12 months before and ≥ 24 months after diagnosis was required. Treatment patterns 2 years after diagnosis were analyzed descriptively overall and by race/ethnicity. The sample included 682 newly diagnosed and treated pwMS (non-Hispanic Black, n = 99; non-Hispanic White, n = 479; Hispanic, n = 35; other/unknown race/ethnicity, n = 69). The mean time from diagnosis to DMT initiation was 4.9 months in all pwMS. Glatiramer acetate and dimethyl fumarate were the most common first-line DMTs in non-Hispanic Black (28% and 20% respectively) and Hispanic pwMS (31%, 29%); however, glatiramer acetate and ocrelizumab were the most common in non-Hispanic White pwMS (33%, 18%). Use of first-line high-efficacy DMTs was limited across all race/ethnicity subgroups (11-29%), but uptake increased in non-Hispanic Black and White pwMS over the study period. Use of high-efficacy DMTs was low across all race/ethnicity subgroups of newly diagnosed pwMS in the US, including populations at a greater risk of experiencing rapid disease progression and severe disability.

A comparison of serum inflammatory parameters in progressive forms of multiple sclerosis

IntroductionMultiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system. Primary progressive MS (PPMS) is diagnosed in approximately 10–15 % of MS patients. Disease-modifying therapies (DMT) are less effective in modifying the course of progressive types of MS. It seems that inflammatory processes differ in the MS subtypes. ObjectivesThe objective of this study was to assess differences in the inflammatory parameters between PPMS and other courses of MS. Materials and methodsA total of 84 subjects were included in the study. The study group was divided according to the course of MS into the following categories: PPMS (n = 24); SPMS—secondary progressive multiple sclerosis (n = 14); RRMS—relapsing–remitting multiple sclerosis (n = 46). PPMS patients were further divided into treated with ocrelizumab and treatment-naive groups. The concentrations of serum inflammatory parameters were evaluated. ResultsPPMS and SPMS significantly differed in the serum levels of sCD30, gp130, sIL-6R alpha, osteopontin, pentraxin-3 and sTNF-R1. The serum concentrations of IFN-alpha2, IL-10, IL-20, IL-29 and osteopontin significantly differed between PPMS and RRMS. The serum levels of BAFF, IL-19, IL-20, pentraxin-3, s-TNF-R1 and s-TNF-R2 significantly differed between PPMS treated with ocrelizumab and treatment-naive. ConclusionAlthough inflammatory processes take part in the pathogenesis of all types of MS, they differ between MS courses. Serum inflammatory parameters seem to be promising biomarkers in helping to differentiate courses of MS, and in assessing reactions to DMT treatment. Further investigations on their usage are required.

Fatigue and Other Patient-Reported Outcomes in Patients With RRMS who Switched to Ocrelizumab: 4-Year Data From CASTING-LIBERTO (P6-3.010)

Fatigue and Other Patient-Reported Outcomes in Patients With RRMS who Switched to Ocrelizumab: 4-Year Data From CASTING-LIBERTO (P6-3.010)

Approach to Balancing Risk in Multiple Sclerosis Management: a Worldwide Practice Survey (P14-3.013)

Approach to Balancing Risk in Multiple Sclerosis Management: a Worldwide Practice Survey (P14-3.013)

The effectiveness of teriflunomide in patients with multiple sclerosis in China: a real-world comparison to no DMT treatment in the first year after diagnosis.

Teriflunomide is a first-line oral immunomodulatory agent approved in China for the treatment of relapsing multiple sclerosis. To compare the treatment outcomes of teriflunomide and no disease-modifying therapy (DMT) treatment (in first year) in multi-center real-world Chinese multiple sclerosis patients. Retrospective study. This study was conducted in five tertiary hospitals in different geographical regions of China. We collected clinical data of patients treated with teriflunomide and no DMT treatment (in first year) between 1 January 2017 and 31 August 2021. The effectiveness of teriflunomide was described. Potential factors influencing the effectiveness of teriflunomide were investigated. A total of 372 patients treated with teriflunomide and 148 no DMT treatment patients were included. A total of 292 patients were treated with teriflunomide for at least 6 months, described as a stable teriflunomide cohort. The annualized relapse rate was significantly lower in the stable teriflunomide cohort than in the no DMT treatment cohort (0.23 ± 0.47 versus 0.87 ± 0.67, p < 0.001). The mean Expanded Disability Status Scale (EDSS) score of the stable teriflunomide cohort (1.77 ± 1.62) was slightly different from that of the no DMT treatment cohort (2.09 ± 2.00). A previous annualized relapse rate of ⩾1, a previous EDSS score of ⩾2, and a long disease duration of ⩾5 years were associated with better clinical effectiveness. Teriflunomide is associated with a lower relapse rate and less disability accumulation in Chinese patients with multiple sclerosis.

The Epidemiology, Treatment Patterns and Economic Burden of Different Phenotypes of Multiple Sclerosis in Italy: Relapsing-Remitting Multiple Sclerosis and Secondary Progressive Multiple Sclerosis

A retrospective analysis of real-world data was performed to assess the epidemiology and economic burden of multiple sclerosis (MS), relapsing-remitting MS (RRMS), and secondary-progressive MS (SPMS) in Italy. An observational study on administrative databases from a sample of Italian entities was carried-out. Between 01/2010-12/2017, patients with ≥1 MS diagnosis code (ICD-9-CM:340 and/or exemption code:046) and/or ≥1 disease-modifying therapies (DMTs) prescription, were included. Among MS-cohort, SPMS patients were identified by ≥2 hospitalizations or by ≥2 drug prescriptions related to MS progression. MS patients not fulfilling SPMS criteria were included as RRMS. Mean annual healthcare costs were reported during follow-up and stratified by DMT treatment/untreatment. Overall, 9543 MS patients were included; 8397 with RRMS and 1146 with SPMS. Estimated prevalence of MS was 141.6/100,000 inhabitants (RRMS 124.4/100,000 and SPMS 17.2/100,000). Mean annual cost for untreated and treated patient was respectively: €3638 and €11796 (MS-cohort), €3183 and €11486 (RRMS-cohort), €6317 and €15511 (SPMS-cohort). The first-line DMT treatment duration averaged 27.4 ± 22.8 months; the mean cost was 19004€ for the whole period. The second-line DMT treatment lasted on average 31.1 ± 24.5 months; the mean cost was 47293€ for the whole period. This study provided insights into the MS epidemiology in Italy and its economic burden. Healthcare costs associated with MS management were mainly driven by DMTs expenditure. A trend of higher healthcare-resource consumption was observed among SPMS-cohort.

Assessing the Cost-effectiveness of a Hypothetical Disease-modifying Therapy With Limited Duration for the Treatment of Early Symptomatic Alzheimer Disease

PurposeClinical trials have produced promising results for disease-modifying therapies (DMTs) for Alzheimer’s disease (AD); however, the evidence on their potential cost-effectiveness is limited. This study assesses the cost-effectiveness of a hypothetical DMT with a limited treatment duration in AD. MethodsWe developed a Markov state–transition model to estimate the cost-effectiveness of a hypothetical DMT plus best supportive care (BSC) versus BSC alone among Americans living with mild cognitive impairment (MCI) due to AD or mild AD. AD states included MCI due to AD, mild AD, moderate AD, severe AD, and death. A hypothetical DMT was assumed to confer a 30% reduction in progression from MCI and mild AD. The base case annual drug acquisition cost was assumed to be $56,000. Other medical and indirect costs were obtained from published literature or list prices. Utilities for patients and caregivers were obtained from the published literature and varied by AD state and care setting (community care or long-term care). We considered 3 DMT treatment strategies: (1) treatment administered until patients reached severe AD (continuous strategy), (2) treatment administered for a maximum duration of 18 months or when patients reached severe AD (fixed-duration strategy), and (3) 40% of patients discontinuing treatment at 6 months because of amyloid plaque clearance and the remaining patients continuing treatment until 18 months or until they reached severe AD (test-and-discontinue strategy). Incremental cost-effectiveness ratios (ICERs) were calculated as the incremental cost per quality-adjusted life-year (QALY) gained. FindingsFrom the health care sector perspective, continuous treatment with a hypothetical DMT versus BSC resulted in an ICER of $612,354 per QALY gained. The ICER decreased to $157,288 per QALY gained in the fixed-duration strategy, driven by large reductions in treatment costs. With 40% of patients discontinuing treatment at 6 months (test-and-discontinue strategy), the ICER was $125,631 per QALY gained. In sensitivity and scenario analyses, the ICER was the most sensitive to changes in treatment efficacy, treatment cost, and the initial population AD state distribution. From the modified societal perspective, ICERs were 6.3%, 20.4%, and 25.1% lower than those from the health care sector perspective for the continuous, fixed-duration, and test-and-discontinue strategies, respectively. ImplicationsUnder a set of assumptions for annual treatment costs and the magnitude and duration of treatment efficacy, DMTs used for a limited duration may deliver value consistent with accepted US cost-effectiveness thresholds.

The Patient and Clinician Assessment of Gastrointestinal (GI) Related Adverse Events Associated with Oral Disease-Modifying Therapies in Multiple Sclerosis: A Qualitative Study.

IntroductionCurrent guidelines for relapsing-remitting multiple sclerosis (RRMS) call for treatment with disease-modifying therapies (DMTs) early in the disease to prevent relapses and accumulation of neurologic impairment and disability. However, patients taking certain oral DMTs may experience gastrointestinal (GI)-related adverse events (AEs), particularly at dose titration. We conducted qualitative research with healthcare professionals (HCPs) and patients in Canada to contextualize their experiences with three oral DMTs: dimethyl fumarate (Tecfidera®), fingolimod (Gilenya®), and teriflunomide (Aubagio®). The objectives of this study were to (1) gather qualitative data to better understand the patient and HCP experience of GI AEs in oral MS DMT treatment in Canada and (2) determine to what extent two patient-reported outcome (PRO) instruments used in recent oral DMT trials capture what is important to patients regarding GI AEs in oral MS DMT treatment (content validity) and to provide qualitative data to help interpret PRO scores.MethodsThis was a qualitative, non-interventional, descriptive, cross-sectional study comprising HCP and patient interviews conducted in English and French, using a 1:1 semi-structured interview approach.ResultsPatients reported 16 unique GI AE concepts related to oral DMTs. The most commonly reported symptoms were diarrhea, indigestion, and nausea. While patients acknowledged the negative impact associated with GI-related AEs, most characterized the treatment experience as positive, focusing on preference for oral administration, perceived efficacy of DMTs in terms of lack of MS relapses, slowed progression of their disease, and improvement in MS symptoms. Results supported the content validity (relevance, comprehension, and comprehensiveness) of the two PROs assessed. HCP feedback reinforced patient perspectives on both GI concepts and the two PRO instruments.ConclusionOutcomes of these research activities include experiential data on the symptom and impact experience of oral DMTs in MS from both patients and HCPs that contribute to the process of determining therapeutic value.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02250-x.

024 CLARITY study: efficacy outcomes among patients receiving disease-modifying therapies prior to treatment with cladribine tablets

BackgroundCladribine tablets 10mg (cumulative dose 3.5mg/kg [CT3.5] over 2 years) showed efficacy vs placebo in patients with relapsing-remitting multiple sclerosis in the CLARITY study. This post-hoc analysis investigated efficacy outcomes for patients with a history of disease-modifying therapy (DMT) use prior to entering CLARITY.MethodsCLARITY included patients previously treated with 0–2 DMTs (patients treated with &gt;2 DMTs were excluded). Analysis of efficacy, annualised relapse rate (ARR), relapse-free rate, MRI activity, and time to 3-month and 6-month confirmed disability progression (CDP), were stratified by prior DMT therapy. P-Values &lt;0.05 were considered nominally significant.ResultsPrior DMT patients were randomised to CT3.5 (n=110) and placebo (n=132). Treatment with CT3.5 vs placebo resulted in a nominally significant reduction in ARR (0.22 vs 0.42; P&lt;0.005), higher relapse-free rate (70.4% vs 55.9%; P=0.0204), numerically lower risk of 3-month CDP (hazard ratio [HR]=0.64, P=0.1589) and 6-month CDP (HR=0.62, P=0.2071), and reductions in brain lesion counts (P&lt;0.001 for each lesion type).ConclusionsPatients who received prior DMT treatment showed significant improvements in efficacy outcomes with CT3.5 compared to placebo. Findings therefore support a consistent effect of cladrib- ine tablets across a broad range of patients, including patients who have used other DMTs.CLARITY:NCT00213135dominic.jack@merckgroup.com

A cross-sectional analysis of persistence to disease-modifying therapies in treatment naïve and experienced patients with relapsing multiple sclerosis at a health-system specialty pharmacy

BackgroundPatients with relapsing multiple sclerosis (RMS) are maintained on disease-modifying therapy (DMT) to prevent disease progression. Reported persistence rates to DMTs are varied and concerningly low. Limited data exists on long-term persistence rates and reasons for DMT discontinuation in patients with RMS. This study evaluated long-term DMT persistence, rates and reasons for DMT discontinuation or switch, specialty pharmacist involvement in DMT treatment transitions, and predictors associated with non-persistence in treatment naïve and experienced patients. MethodsWe performed a single-center retrospective, cross-sectional review of patients with RMS and ≥3 fills of DMT from a health-system specialty pharmacy (May-October 2017). Patients were followed for 3 years to determine DMT persistence, defined as the time a patient remained on index DMT. Descriptive statistics were used to summarize sample characteristics and outcomes. The Kaplan-Meier estimation method was used to estimate the probability of remaining persistent and we used the Cox proportional hazards regression model to analyze the primary outcome. Rates and reasons for DMT discontinuation were identified via pharmacy claims and confirmed via chart review of the electronic health record. ResultsThe study included 540 patients, of which 41 (7.6%) were treatment naïve. Over 3 years, 193 (36%) patients remained on index DMT. The probability of remaining persistent for 3 years was 0.51 (95% confidence interval [CI] 0.47–0.56) and median time on index DMT was 642 days (interquartile range 317–1096). For the 347 patients that did not continue index DMT: 91 (26%) discontinued, 136 (39%) switched to a new DMT, 92 (27%) transferred care to a new specialty pharmacy or provider, 21 (6%) were lost to follow-up, and 7 (2%) died. Common reasons for DMT discontinuation or switch were insurance formulary change, side effects, clinical decline, and stable disease. Specialty pharmacists initiated 6 (7%) DMT discontinuations and 49 (36%) DMT switches. A strong non-linear relationship existed between age and risk of non-persistence (p = 0.003). Patients on an injectable index DMT were 1.5 times more likely to be non-persistent than those on an oral DMT (95% CI 1.1–2.1, p = 0.012) and patients with non-commercial insurance were 1.4 times more likely to be non-persistent (95% CI 1.02–2.0, p = 0.040). ConclusionsLong-term persistence to DMTs is low, with many patients switching or discontinuing DMT treatment. Specialty pharmacists identify the need for DMT discontinuation or switch and are uniquely positioned to assist during therapy transitions.

System-Level Variation in Multiple Sclerosis Disease-Modifying Therapy Utilization: Findings From the Multiple Sclerosis Continuous Quality Improvement Research Collaborative.

The Multiple Sclerosis Continuous Quality Improvement (MS-CQI) Collaborative is the first multicenter improvement research collaborative for multiple sclerosis (MS). The main objective of this study is to describe baseline system-level variation in disease-modifying therapy (DMT) utilization across 4 MS centers participating in MS-CQI. Electronic health record data from the first year of the 3-year MS-CQI study were analyzed. Participants were adults ≥ 18 years with MS presenting to any of the 4 MS-CQI centers. DMT utilization was categorized into oral, infusion, and injection types. Multinomial logistic regression was used to investigate associations between centers and DMT utilization. Overall, 2,029 patients were included in the analysis. Of those patients, 75.1% were female, mean age was 50 years, and 87.4% had relapsing-remitting MS. Overall, 32.7% were on an oral DMT, 23.5% on an infusion DMT, and 43.9% on an injection DMT. Overall, statistically significant differences (p < 0.01) were observed across centers for proportions of patients who received oral, infusion, and no DMTs. There were also overall significant differences (p < 0.01) across MS types for proportions of encounters who received oral, infusion, injection, no DMTs, and mean age varied significantly across centers. System-level effects on MS treatment and outcomes have not been previously studied and our findings contribute initial evidence concerning system-level variation in DMT utilization. Results suggest system-level variation in DMT utilization (ie, after adjusting for individual level factors, MS center or location of care a person with MS engages in care influences DMT treatment choices), resulting in a lack of standardization in DMT management. Continued research and improvement efforts targeting system-level performance could improve outcomes for people with MS.

The effect of national disease-modifying therapy subsidy policy on long-term disability outcomes in people with multiple sclerosis

Background: Disease-modifying therapies (DMTs) are used to treat people with relapsing-onset multiple sclerosis (ROMS), but our knowledge is largely limited to their short-term effects. Objective: To determine (1) the impact of national-level DMT subsidy policy on DMT use and health outcomes in people with MS (PwMS) and (2) the long-term effects of DMT on disability and quality of life (QoL; 5-level EQ-5D version (EQ-5D-5L) utility value). Methods: This observational cohort study compared Australian and New Zealand populations with different levels of DMT availability 10–20 years post-ROMS diagnosis. Between-country differences were assessed using standardised differences. Associations were assessed with multivariable linear regression models. Results: We recruited 328 Australians and 256 New Zealanders. The Australian cohort had longer DMT treatment duration, greater proportion of disease course treated and shorter duration between diagnosis and starting DMT. The Australian cohort had lower median Expanded Disability Status Scale (EDSS) (3.5 vs 4.0) and Multiple Sclerosis Severity Score (MSSS) (3.05 vs 3.71) and higher QoL (0.71 vs 0.65). In multivariable models, between-country differences in disability and QoL were largely attributed to differential use of DMT. Conclusions: This study provides evidence for the impact of national-level DMT policy on disability outcomes in PwMS. Where DMTs are more accessible, PwMS experienced less disability progression and improved QoL 10–20 years post-diagnosis.

The Disease-Modifying Therapies of Relapsing-Remitting Multiple Sclerosis and Liver Injury: A Narrative Review.

In this narrative review, we analyze pre-registration and post-marketing data concerning hepatotoxicity of all disease-modifying therapies (DMTs) available for the treatment of relapsing-remitting multiple sclerosis, including beta interferon, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, cladribine, natalizumab, alemtuzumab, and ocrelizumab. We review the proposed causal mechanisms described in the literature and we also address issues like use of DMTs in patients with viral hepatitis or liver cirrhosis. Most data emerged in the post-marketing phase by reports to national pharmacovigilance agencies and published case reports or case series. Serious liver adverse events are rare, but exact incidence is largely unknown, as are predictive factors. Unfortunately, none of the DMTs currently available for the treatment of multiple sclerosis is free of potential hepatic toxic effects. Cases of acute liver failure have been reported for beta-interferon, fingolimod, natalizumab, alemtuzumab, and ocrelizumab by different mechanisms (idiosyncratic reaction, autoimmune hepatitis, or viral reactivation). Patients with multiple sclerosis should be informed about possible hepatic side effects of their treatment. Most cases of liver injury are idiosyncratic and unpredictable. The specific monitoring schedule for each DMT has been reviewed and the clinician should be ready to recognize clinical symptoms suggestive for liver injury. Not all DMTs are indicated in cirrhotic patients. For some DMTs, screening for hepatitis B virus and hepatitis C virus is required before starting treatment and a monitoring or antiviral prophylaxis schedule has been established. Beta interferon, glatiramer acetate, natalizumab, and alemtuzumab are relatively contraindicated in autoimmune hepatitis due to the risk of disease exacerbation.

Association between multiple sclerosis disease severity and adherence to disease-modifying therapies.

BACKGROUND: For multiple sclerosis (MS) patients taking disease-modifying therapies (DMTs), adherence to treatment is a key component of achieving beneficial outcomes, such as delayed disease progression and the reduction and prevention of symptoms and relapses. OBJECTIVES: The aim of this study was to assess the impact of a claims-based measure of MS disease severity on DMT adherence in a one-year study period. METHODS: Patients were identified from Humana Medicare Advantage claims data from January 1, 2013 to December 31, 2015. Patients over the age of 18 with at least 12 months of continuous enrollment and > 1 outpatient MS visit with DMT use prior to the index date were included. Patients who switched DMT type (oral, platform, IV) during the study period were excluded. Medication possession ratios (MPR) for DMTs were calculated from pharmacy and medical claims over 12 months of claims data, and a previously developed claims algorithm was used to determine MS disease severity. Patients with MPRs of 0.8 or higher were considered adherent to DMT treatment. Multivariable logistic regression was used to evaluate the association of MS disease severity, gender, DMT type, and age category with DMT adherence. RESULTS: The study population of 3,347 patients had an average MPR of 84.7 (75% were classified as adherent). Multivariable logistic analysis demonstrated that compared to the 18-45 age group, the 46-64 and 65+ age groups were 1.33 (OR: 1.33 [95% CI 1.08-1.64]) and 1.55 (OR: 1.55, [95% CI 1.18-2.05]) times more likely to be adherent. Patients with a high level of MS disease severity were 53% (OR: 0.47, [95% CI 0.36-0.62]) less likely to be adherent compared to those with low MS disease severity. No significant difference was identified for gender or DMT type (oral, platform, or IV). CONCLUSIONS: Increased age and lower MS disease severity were associated with better DMT adherence. MS disease severity should be considered when assessing risk for low DMT adherence. DISCLOSURES: No funding supported this project. The authors have nothing to disclose. Preliminary results were previously presented virtually at AMCP Annual 2020 in April 2020.

PND1 IMPACT of EARLY Disease Modifying Therapy (DMT) Treatment Initiation and Use of High-Efficacy (HET) on Clinical and Health Outcomes in Patients with Multiple Sclerosis (MS)

To explore the impact of early DMT treatment initiation and use of HET on clinical and health outcomes in patients with MS. A targeted literature review was conducted using Embase (including Medline) to identify studies published from January 2006-March 2020. Search terms included clinical-outcomes: annualized relapse rate (ARR), disability progression, magnetic resonance imaging (MRI) outcomes; and health-related outcomes: quality of life (QoL), work-productivity, therapy persistence, and healthcare resource utilization (HCRU). Among the screened studies, 69 were included in this review (50 observational studies, 18 clinical trials, and 1 systematic review; 35 US/Canadian, 20 global, 12 European, and 2 Australian studies). ARR and disease progression were the most common outcomes in the included studies. Inhibition of MS disability, slower disease progression, lower ARR, improved persistence/adherence, cost-savings, and decrease in HCRU were achieved if a DMT was initiated early following diagnosis. Definition of HET varied across studies; while most studies identified infused DMTs as HET, some studies also included fingolimod as HET. Use of HET was associated with improvements in QoL, work productivity, therapy persistence, and reduction in hospitalizations. Of 4 studies which evaluated early initiation of HET (E-HET), all favored the induction vs escalation approach. Overall, several studies found that E-HET in the MS disease process produced greater efficacy in reducing relapse rate, MRI-activity, brain atrophy, and long-term disease progression. However, no studies were identified that addressed the effect of E-HET on health-related outcomes. Emerging evidence suggests that initiating E-HET in MS leads to better clinical outcomes while HET use is associated with improved health-related outcomes. However, a need exists to better understand the humanistic and economic benefits of initiating E-HET in the MS disease course and in standardizing the definition of HET to better inform treatment decision-making for patients and providers.