Oral Disease-modifying Therapies Research Articles

The implications of suboptimal year-1 outcomes with disease-modifying therapy in employees with multiple sclerosis

Aim Multiple sclerosis (MS) poses a substantial employer burden in medically related absenteeism and disability costs due to the chronic and debilitating nature of the disease. Although previous studies have evaluated relapse, nonadherence, discontinuation, and switching individually, little is known about their overall collective prevalence and implications in employees with MS treated with disease-modifying therapies (DMTs). This study evaluated the proportion of employees with MS with suboptimal DMT year-1 outcomes and to quantify the clinical and economic burden of suboptimal year-1 outcomes from a US employer perspective. Materials and Methods Employees with MS were selected from the Workpartners database. Eligibility criteria were: ≥2 MS diagnosis claims (ICD-9-CM 340.xx/ICD-10-CM G35) from January 1, 2010–March 31, 2019, ≥1 once-/twice-daily oral or self-injectable DMT claim (first claim = index), continuous eligibility 6-months pre-/1-year post-index, no baseline DMT, and age 18–64 years. Suboptimal year-1 outcomes included: non-adherence (proportion of days covered <80%), discontinuation (gap >60 days), switch, or relapse (MS-related hospitalization, emergency room visit, or outpatient visit with corticosteroid). A two-part logistic-generalized linear model evaluated costs. Results Of 488 eligible patients, half (n = 247; 50.6%) had suboptimal year-1 outcomes (39.5% non-adherence, 9.8% discontinuation, 10.9% switching, 20.7% relapse; not mutually exclusive). Employees with suboptimal year-1 outcomes had higher all-cause medical ($12,730 vs. $6,428; p < 0.0001), MS-related medical ($5,444 vs. $2,652; p < 0.0001), non-DMT pharmacy ($2,920 vs. $2,169; p = 0.0199), sick leave ($1247 vs. $908; p = 0.0274), and short-term disability ($934 vs. $146; p = 0.0001) costs. Long-term disability ($751 vs. $0; p = 0.1250) and Workers’ Compensation ($56 vs. $24; p = 0.1276) did not significantly differ. Limitations Administrative claims lack clinical information. Results may not be generalizable to other patients or care settings. Conclusions Half of the employees with MS in this sample had suboptimal year-1 outcomes (i.e. non-adherence, discontinuation, switching, or relapse). These suboptimal year-1 outcomes were associated with greater medical, sick leave, and short-term disability costs.

Quality of life among injectable and oral disease-modifying therapy users in the Pacific Northwest Multiple Sclerosis Registry

BackgroundNine oral disease-modifying therapies (DMTs) have been approved for the treatment of multiple sclerosis (MS) in the United States. Few studies have examined self-reported quality of life (QoL) and functional status outcomes among patients who switch to oral medications from injectable MS therapies. This study compares self-reported QoL and disability status between participants switching from injectable to oral DMTs, to those who stay on injectable DMTs continuously for the same time period.MethodsLongitudinal data were assessed from relapsing MS participants in the Pacific Northwest MS Registry completing a minimum of two surveys between 2012 and 2018 with a maximum of 36 months between surveys. Stayers were defined as those who remained on injectable DMTs continuously from Time 1 to Time 2; switchers were those who switched from injectable to either fingolimod, teriflunomide or dimethyl fumarate during the same time interval. Outcomes of interest were physical and psychological QoL, measured by the Multiple Sclerosis Impact Scale (MSIS-29), and disability, measured by the Patient Determined Disease Steps (PDDS). To analyze the effect of switching to oral DMT on outcomes at Time 2, a one-to-two propensity score matching (PSM) was used to match switchers to stayers. Outcomes at Time 2 were analyzed using paired t-test for QoL scores, and Stuart Maxwell test for PDDS as a categorical variable.ResultsAmong 2385 participants who returned consecutive yearly surveys, 413 met the inclusion criteria for stayers and 66 for switchers. After one-to-two PSM, 124 stayers were matched to 62 switchers. Paired t-test showed no differences between switchers and stayers for physical (mean difference: − 0.41; [95% confidence interval CI: − 3.3-2.4]; p = 0.78) or psychological (mean difference: − 0.23; [95% CI, − 1.6- 1.1]; p = 0.74) QoL. Additionally, no differences were seen between switchers and stayers in self-reported disability status.ConclusionsMS registry participants who switched to an oral DMT from injectable showed no significant differences in QoL or self-reported disability status compared to those remaining on injectable DMT continuously in the same time period.

PND9 Comparative Efficacy and Safety of Ozanimod Versus Teriflunomide for Relapsing-Remitting Multiple Sclerosis: A Matching-Adjusted Indirect Comparison

Ozanimod is a selective S1P1,5 modulator approved in the US for relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head data, matching-adjusted indirect comparisons (MAICs) can be used to compare oral disease-modifying therapies (DMTs) in RRMS. The objective of this study was to compare the relative efficacy/safety of ozanimod 1.0 mg and teriflunomide (TEF) 14 mg. A systematic literature review identified clinical trials evaluating efficacy/safety of ozanimod and TEF. Individual patient data (IPD) were obtained from the ozanimod SUNBEAM and RADIANCE Part B trials, and aggregate-level data were obtained from 6 TEF trials. Heterogeneity was observed between ozanimod and TEF trials in Expanded Disability Status Scale scores, gadolinium-enhanced lesions, disease duration from symptom onset, prior relapse and DMT use, age, sex, region, and weight. An unanchored (no common comparator) MAIC was conducted adjusting for imbalances between studies by weighting the IPD for ozanimod to match mean baseline characteristics for TEF. Outcomes of interest were assessed: annualized relapse rate (ARR), proportion of patients relapsed, confirmed disability progression (CDP) sustained for 12 and 24 weeks, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. After matching, baseline patient characteristics were balanced between ozanimod and TEF. Compared with TEF, ozanimod demonstrated improvements in ARR (rate ratio [RR]: 0.73; 95% CI: 0.62–0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44–0.70), overall AEs (OR: 0.35; 95% CI: 0.29–0.43), SAEs (OR: 0.53; 95% CI: 0.37–0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09–0.21) and similar CDP at 12 (RR: 0.80; 95% CI: 0.61–1.05) and 24 (RR: 0.80; 95% CI: 0.59–1.08) weeks. Ozanimod was associated with improved relapse outcomes and lower risks of AEs over 1–2 years of follow-up compared with TEF, with no differences in CDP.

Work Productivity Outcomes Associated with Ocrelizumab Compared with Other Disease-Modifying Therapies for Multiple Sclerosis.

ObjectiveThis study evaluated work and activity impairment in patients with multiple sclerosis (MS) treated with ocrelizumab (OCR) versus other disease-modifying therapies (DMTs).MethodsData were obtained from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis. Patients with relapsing–remitting or secondary progressive MS who completed surveys in 2018 and 2019 and received ≥ 6 months of an eligible therapy, including OCR, injectable therapy, and oral therapy, were included. Outcomes were assessed using the patient-reported Work Productivity and Activity Impairment questionnaire. Doubly robust estimation, which combined propensity score weighting and regression modeling, was used to compare treatments, controlling for baseline clinical and demographic characteristics.ResultsThis study included 630 patients (OCR, n = 90; injectable DMT, n = 224; oral DMT, n = 316) with a mean (standard deviation) age of 42 (11) years. A greater proportion of OCR-treated patients had an Expanded Disability Status Scale score of ≥ 3 at treatment initiation compared with those receiving oral and injectable DMTs (51 vs. 15% and 15%, respectively), and a smaller proportion of OCR-treated patients received treatment for ≥ 1 year (43 vs. 90% and 92%, respectively). OCR-treated patients had higher odds of employment [odds ratio (95% confidence interval) 3.4 (1.5–7.7) vs. oral DMT, 5.6 (2.6–12.0) vs. injectable DMT], lower overall work productivity loss [difference (95% confidence interval) − 10.0% (− 6.1 to − 15.0%) vs. oral DMT, − 13.0% (− 8.5 to − 17.0%) vs. injectable DMT] and lower activity impairment [difference (95% confidence interval) − 11% (− 7.1 to − 16.0%) vs. oral DMT, − 9.7% (− 5.0 to − 14.0%) vs. injectable DMT].ConclusionThis real-world evidence suggests that patients with MS treated with OCR experience lower work and activity impairment than patients treated with other DMTs.Electronic supplementary materialThe online version of this article (10.1007/s40120-020-00224-1) contains supplementary material, which is available to authorized users.

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

PurposeAlthough 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). MethodsIBM 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. FindingsOf 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. ImplicationsThe 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.

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

ObjectivesThe aim of this study was to examine the indirect burden of employed multiple sclerosis (MS) patients initiating disease-modifying therapies (DMTs) in the US.MethodsDMT-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.ResultsA 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).ConclusionsEmployed 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.Electronic supplementary materialThe online version of this article (10.1007/s41669-020-00233-8) contains supplementary material, which is available to authorized users.

Medication adherence/persistence among patients with active multiple sclerosis in Finland.

ObjectivesTo explore adherence, persistence, and treatment patterns in patients with multiple sclerosis (MS) in Finland treated with disease‐modifying therapies (DMTs) for active MS in 2005‐2018.Materials and MethodsThe study cohort was identified using the Drug Prescription Register of Social Insurance Institute, Finland. All patients had at least one prescription of glatiramer acetate (GA), beta‐interferons, teriflunomide, or delayed‐release dimethyl fumarate (DMF). Adherence was calculated using proportion of days covered (PDC) (cutoff ≥0.8). Time to non‐persistence was calculated by the number of days on index DMT treatment before the first treatment gap (≥90 days) or switch and analyzed with time‐to‐event methodology.ResultsThe cohort included 7474 MS patients (72.2% female; mean age 38.9 years). Treatment switches were steady over 2005‐2012, peaked in 2015. PDC means (standard deviations) were GA, 0.87 (0.17); beta‐interferons, 0.88 (0.15); DMF, 0.89 (0.14); teriflunomide, 0.93 (0.10). Adherence frequencies were GA, 78.4%; beta‐interferons, 81.3%; DMF, 86.9%; teriflunomide, 91.7%. Logistic regression showed that age group, DMT and the starting year, sex, and hospital district independently affected adherence. Patients receiving teriflunomide and DMF, males, and older patients were more likely to persist on treatment. There was no difference in persistence between patients prescribed teriflunomide and DMF, or between GA and beta‐interferons.ConclusionsOral DMTs had greater adherence and persistence than injectable DMTs.

The efficacy and safety of oral disease-modifying therapies for relapsing-remitting multiple sclerosis: A systematic review

Background: Although widely used, first-line injectable medicines for the treatment of multiple sclerosis (MS) remain an issue of efficacy and adherence. Recently, new oral medications for MS have contributed to dramatic improvements in MS treatment. This study aims to evaluate the safety and efficacy of oral disease-modifying drugs (DMDs) used in relapsing-remitting MS (RRMS). Methods: A systematic review was conducted on related databases including PubMed, Scopus, Cochrane, and Web of Science up to April 2020. The screening of the studies and their quality assessment was carried out independently by the two authors. Results: Three studies fulfilled the predefined criteria of inclusion. One of them compared teriflonomide with subcutaneous interferon beta-1a (IFN β-1a), another compared oral fingolimod with intramuscular (IM) IFN β-1b, and the third article compared oral fingolimod with IM IFN β-1a. No eligible study was found for dimethyl fumarate (DMF). The results indicated that while the efficacy of fingolimod was more than IFN β (IM β-1a and β-1b), teriflunomide 7 mg had less efficacy than subcutaneous IFN β-1a. Regarding safety, the results indicated that the proportion of diabetic patients with adverse events (AEs) in the fingolimod group was higher than in the IFN β-1b group and the overall occurrence of AEs was similar between teriflunomide and IFN β-1a groups. Conclusion: There is evidence for the effectiveness of fingolimod in reducing annualized relapse rates (ARRs) and improving magnetic resonance imaging (MRI) findings, but the evidence does not support the effectiveness of teriflunomide and further studies are required to determine its efficacy. Also, fingolimod is associated with more side effects than IFN β-1b, but there is no evidence to suggest any difference in side effects between teriflunomide and IFN β-1a.

Dimethyl fumarate vs Teriflunomide: an Italian time-to-event data analysis.

The introduction of oral disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) changed algorithms of RRMS treatment. To compare the effectiveness of treatment with dimethyl fumarate (DMF) and teriflunomide (TRF) in a large multicentre Italian cohort of RRMS patients. Patients with RRMS who received treatment with DMF and TRF between January 1st, 2012 and December 31st, 2018 from twelve MS centers were identified. The events investigated were "time-to-first-relapse", "time-to-Magnetic-Resonance-Imaging (MRI)-activity" and "time-to-disability-progression". 1445 patients were enrolled (1039 on DMF, 406 on TRF) and followed for a median of 34months. Patients on TRF were older (43.5 ± 8.6 vs 38.8 ± 9.2years), with a predominance of men and higher level of disability (p < 0.001 for all). Patients on DMF had a higher number of relapses and radiological activity (p < .05) at baseline. Time-varying Cox-model for the event "time-to-first relapse" revealed that no differences were found between the two groups in the first 38months of treatment (HRt<38DMF = 0.73, CI = 0.52 to 1.03, p = 0.079). When the time-on-therapy exceeds 38months patients on DMF had an approximately 0.3 times lower relapse hazard risk than those who took TRF (HRt>38DMF = 3.83, CI = 1.11 to 13.23, p = 0.033). Both DMTs controlled similarly MRI activity and disability progression. Patients on DMF had higher relapse-free survival time than TRF group after the first 38 months on therapy.

PND120 TREATMENT PATTERNS AMONG PATIENTS WITH MULTIPLE SCLEROSIS INITIATING SECOND-LINE DISEASE-MODIFYING THERAPY

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 within the context of MS relapses. We describe MS relapses related to treatment patterns among patients who switch treatment after their first DMT. IBM MarketScan research databases were used to identify adult MS patients who switched DMTs (index-first switch) after being newly treated with a prior DMT from 01/01/2009-04/01/2017 with 12 months of continuous enrollment pre- and post-index. Non-persistence was defined as discontinuing (>60 days without DMT) or switching DMTs. MS relapses were defined using a validated claims-based algorithm. In total, 4,121 MS patients met all inclusion criteria (mean age: 46.4 years; female: 76.2%). First switch to oral agents was predominant (49.6%), followed by injectables (36.5%). Mean time to first switch to oral agents (169.6 days) was longer compared with injectables (110.3 days) or infusions (118.5 days). A smaller proportion of patients experienced a pre-index relapse among those who switched to an oral (37.6%) compared with injectables (44.6%) and infusions (60.7%). Initiation of a second DMT (index) resulted in a 34.2% reduction in relapses post-index. Persistence was low (54.6%) and generally due to discontinuation (88.2%) across treatments. Non-persistence was higher among patients with a relapse within 3 months (52.1%) versus without (44.6%). Among patients with a relapse within 3 months, oral users were more persistent at 12 months (46.2%) than injectable users (38.9%). Among MS patients who switched DMTs, persistence was consistently low regardless of treatment. In these patients, relapses shortly after initiating treatment were associated with lower persistence. Though persistence with oral DMTs was slightly higher than with injectables, overall results indicate poor persistence to second-line therapy and highlight the need to improve long-term persistence with DMTs.

PND93 TREATMENT PATTERNS AND PERSISTENCE TO ORAL AND INJECTABLE MULTIPLE SCLEROSIS DISEASE-MODIFYING THERAPIES BETWEEN THE UNITED STATES AND EUROPE

Prior research in Multiple Sclerosis has shown strong persistence to oral Disease-Modifying Therapies (DMT’s) compared with injectables, with medication possession ratios >85%.1 This study explores utilization patterns of DMT’s between the United States and Europe, including usage of oral versus injectable DMT’s and patient persistence to treatment.

The Impact of Patient Support Programs on Adherence to Disease-Modifying Therapies of Patients with Relapsing-Remitting Multiple Sclerosis in Germany: A Non-Interventional, Prospective Study.

IntroductionDisease-modifying therapies (DMTs) in multiple sclerosis (MS) are chronic therapies, and patients are likely to face challenges in adhering to DMT dosing regimens over time. DMT manufacturers offer patient support programs (PSPs) to increase adherence. PSPs are managed offerings typically encompassing nurse services, phone services, online resources, or mobile offerings. This study evaluated whether PSPs have a positive impact on adherence to DMTs among patients with mild-to-moderate relapsing-remitting multiple sclerosis (RRMS) in Germany, independent of the treatment duration on DMT.MethodsThis was a non-interventional, prospective, cross-sectional, multi-center study with patient-reported outcomes. Patients reported their DMT adherence using patient adherence questionnaires at four visits during an observation period of 24 weeks; PSP participation for this period was reported at the last visit. The primary objective was to evaluate the impact of PSPs on adherence across different DMTs by comparing patients with PSP participation versus no participation; adherence was defined as not missing a single dose of DMT.ResultsOne hundred eighty-four patients were analyzed (mean age: 44.6 years; 73.4% female; mean time on DMT: 7.2 years). Adherence across DMTs was significantly higher for PSP participants (92.9%) compared with non-participants (61.8%) (P = 0.0197). The observed rate of PSP participation (7.6%) was significantly lower than reported in earlier studies (P < 0.0001); PSP awareness among patients analyzed was low (22.3%).ConclusionWe consider this study to have shown that PSPs have a positive impact on adherence to DMTs in MS, independent of the treatment duration on DMT. The majority of PSP participants also believe in this positive effect. PSP participation and patient awareness were low, and real-world adherence levels were found to be higher with self-injectable DMTs than with oral DMTs. In summary, physicians should actively advise patients with MS to participate in PSPs and, together with their patients, consider achievable real-world adherence under different DMTs when deciding MS treatment strategies.

Effect of generic glatiramer acetate on spending and use of drugs for multiple sclerosis.

To estimate changes in costs and utilization trends for disease-modifying therapies (DMTs) from 2011 to 2017 in the US Medicaid program. Using quarterly Medicaid State Drug Utilization Data from 2011 to 2017, we summarize trends in spending, utilization, and costs per prescription for 15 multiple sclerosis (MS) DMTs including brand and generic versions of glatiramer acetate. We use interrupted time series regression to estimate the effect of market entry of generic glatiramer acetate on cost per prescription of other self-administered DMTs. Gross annual expenditures on MS DMTs increased from $453 million to $1.32 billion between 2011 and 2017 within the Medicaid program. Increased spending was primarily driven by increases in per prescription costs, which doubled during the study period. Although total utilization was stable, product specific utilization shifted from injectable to oral DMTs. However, throughout the study, the plurality of utilization was glatiramer acetate. The introduction of generic glatiramer acetate in Q2 of 2015 was associated with an immediate increase of $441 (95% confidence interval [CI] $184-$697; p < 0.001) in the cost per prescription of branded glatiramer acetate followed by a gradual $52 per prescription reduction (95% CI -$86 to -$18) over time. There were minimal changes in the costs for the other DMTs. Spending on MS DMTs in the Medicaid program have more than doubled over the last 7 years primarily as a function of higher costs per prescription. Introduction of a generic glatiramer acetate product in 2015 had nominal effects on overall price trajectories and utilization within the class.

Comparison of health-related quality of life across treatment groups in individuals with multiple sclerosis

BackgroundOutcome measures typically used to evaluate disease modifying therapies (DMTs) provide important information regarding their effects on disease activity, but they do not capture the full impact of living with multiple sclerosis (MS). Patient reported outcome measures (PROs) are increasingly being used to capture an individual's subjective experience of disease. We compared DMTs across a wide range of PRO outcomes in individuals with MS. MethodsSubjects enrolled in SysteMS completed the computer adaptive testing version of the Neuro-QoL within four weeks of a clinical neurological exam. Neuro-QoL measures included the following 11 health-related quality of life (HRQOL) domains: Ability to participate in Social Roles and Activities, Anxiety, Cognitive Function, Depression, Emotional and Behavioral Dyscontrol, Fatigue, Lower Extremity Function (mobility), Positive Affect and Wellbeing, Satisfaction with Social Roles and Activities, Stigma, and Upper Extremity Function (fine motor). Treatments were grouped based on the three main modes of delivery: injectable, oral and infusion. The three treatment groups were compared using linear regression adjusting for two sets of covariates (set 1: age, sex, disease duration and EDSS; set 2: age, sex, disease duration, EDSS and treatment duration). We also compared the individual treatments using linear regression. ResultsAfter adjusting for the first set of clinical and demographic features of MS, there was a difference between treatment groups for Upper Extremity Function and Stigma. Subjects using injectable treatments reported better functioning in terms of Upper Extremity Function and Stigma than subjects using infusion treatments. In addition, subjects using injectable treatments reported better Upper Extremity Function than subjects treated with oral DMTs. When all individual treatments were compared, interferon-treated subjects reported significantly better functioning in terms of Stigma than natalizumab treated subjects. When further adjusting for time on treatment, the group differences were attenuated and no longer statistically significant. ConclusionWe examined differences between MS treatment groups across a wide range of HRQOL outcomes. The results suggest that overall there are few differences between treatments on the physical, cognitive and emotional dimensions of well-being.

Time to treatment failure following initiation of fingolimod versus teriflunomide for multiple sclerosis: a retrospective US claims study

Objective: Disease modifying therapies (DMTs) for multiple sclerosis (MS) aim to delay progression and reduce relapses. Evidence is limited on the comparative effectiveness of the oral DMTs fingolimod and teriflunomide. This study evaluated time to treatment failure among patients with MS who initiated fingolimod versus teriflunomide in real-world settings.Methods: The retrospective cohort included 18–64 year old patients diagnosed with MS who initiated fingolimod or teriflunomide during 12 September 2012 to 30 September 2015 within MarketScan Commercial and Medicare Claims. Patients were followed from treatment initiation (index date) until first treatment failure or censoring. Treatment failure was defined as the first occurrence of MS relapse (identified using a validated algorithm) or treatment discontinuation (≥60 day supply gap). Treatment failure was examined through Kaplan–Meier analysis and multivariable Cox regression adjusting for 1 year baseline factors (age, gender, plan type, region, index year, prior DMT use, baseline relapses, Charlson Comorbidity Index [CCI] and MS symptoms).Results: On average, patients treated with fingolimod (n = 2704) were younger (43.6 versus 49.8 years) with lower CCI (0.4 versus 0.7) and more relapses at baseline (0.46 versus 0.42) than those treated with teriflunomide (n = 1859). Median time to treatment failure was 19.5 months with fingolimod versus 9.6 months with teriflunomide (p < .001). After controlling key demographic and clinical characteristics through multivariable regression, fingolimod was associated with 38.9% lower hazards of treatment failure versus teriflunomide (adjusted hazard ratio = 0.611; 95% CI: 0.559–0.669; p < .001).Conclusions: In a large cohort of US adults with MS, controlling for key baseline characteristics, fingolimod was associated with significantly longer time to treatment failure and lower risk of treatment failure compared with teriflunomide.

PND1 RELAPSE-RELATED OUTCOMES IN PATIENTS WITH MULTIPLE SCLEROSIS TREATED WITH FIRST-LINE DISEASE-MODIFYING THERAPIES

This study compared the annualized relapse rates (ARRs) and risk of relapse in patients with multiple sclerosis (MS) on first-line (F-L) oral vs platform disease-modifying therapies (DMTs). Adult patients with MS who newly initiated platform therapies (interferon or glatiramer acetate) and oral therapies (dimethyl fumarate or fingolimod) from January 2011 to December 2017 were identified using IBM MarketScan research databases. The index date was the first DMT claim date. Patients had ≥1-year pre-index and post-index continuous enrollment and ≥1 MS diagnosis prior to or within 30 days post-index. Relapse rates (ARRs) were annualized for the first 3 years post-index. Generalized linear models were used to compare ARRs, and Cox regression was used to estimate the risk of relapse after adjusting for age, gender, index year, Charlson Comorbidity Index score, baseline relapse, and time from earliest MS diagnosis to F-L DMT. A total of 9,375 MS patients met the study selection criteria; 3,060 patients were treated with F-L oral DMTs and 6,315 were treated with F-L platform DMTs. Patients treated with oral DMTs had significantly lower ARRs than those treated with platform DMTs (year 1 post-index: 0.226 vs 0.185, P<0.0001; years 1-2: 0.208 vs 0.175, P<0.0001; years 1-3: 0.201 vs 0.172, P<0.0001). Similar results were obtained after controlling for covariates (year 1 post-index: 0.217 vs 0.168, P<0.0001; years 1-2: 0.201 vs 0.156, P<0.0001; years 1-3: 0.197 vs 0.149, P<0.0001). F-L oral DMT patients had a reduced risk of experiencing relapse compared with F-L platform patients (year 1: HR=0.822, P<0.0001; years 1-2: HR=0.848, P<0.0001; years 1-3: HR=0.841, P<0.0001). These findings suggest that patients newly treated with oral DMTs had lower relapse rates and reduced risk of relapse compared with those treated with platform therapies over the first 3 years of treatment.

PMS55 TREATMENT PATTERNS AMONG MS PATIENTS NEWLY INITIATING DISEASE-MODIFYING THERAPY

Disease-modifying therapies (DMTs) can reduce multiple sclerosis (MS) relapse rates; understanding treatment patterns and effectiveness in relapse reduction across all available DMTs using real-world data is important. We describe treatment patterns and post-DMT initiation relapses stratified by the number of pre-initiation relapses among newly treated MS patients overall, and by treatment. IBM MarketScan research databases were used to identify adult MS patients newly initiating DMTs (index event) from 01/01/2011-01/04/2016 with 12 months of continuous enrolment pre-index and post-index. MS was determined by ≥2 non-diagnostic claims with an ICD-9-CM (340) or ICD-10-CM (G35) code. Patients had not taken DMTs in the pre-index period. Non-persistence was defined as discontinuing index therapy (>60 days without DMT) or switching DMTs. Relapse was defined using a validated claims-based algorithm. The final sample consisted of 9,378 newly treated MS patients (average age, 46.7 years; 73.3%, female). Patients started with an injectable (65.5%), oral (26.1%), or infusion (8.4%, not shown) DMT. An overall 27% reduction in relapses was observed pre-index to post-index and was highest among those on oral agents (39.4%). Patients without pre-index relapse (vs those with ≥3) were more likely to be relapse-free post-index (81.6% vs 31.4%). Non-persistence was observed in 44.7% of patients, mainly due to discontinuation (90.3%). Patients with and without pre-index relapses had similar 12-month post-index persistence with DMTs (39.6% vs 38.9%); however, persistence was lower for patients with relapse within 3 (49.0% vs 62.1%) or 6 months (48.4% vs 63.2%) post-index. Those on oral agents were most persistent (50.3%) among those relapsing within 3 months. Reduction in MS relapses was observed in those initiating a DMT among treatment-naive MS patients, with better gains among those initiating oral DMTs. However, patients relapsing early during treatment exhibit lower persistence, and there is still an unmet need in these patients.

Patients’ preferences and willingness-to-pay for disease-modifying therapies

BackgroundWhile disease-modifying therapies (DMTs) for multiple sclerosis (MS) treatments are costly, patient valuation of DMTs has not been examined. The objective of this study was to examine patients' preferences and willingness-to-pay (WTP) for DMTs. MethodsSix attributes (i.e., number of relapses, percentage of disability progression, percentage of severe adverse events, route of administration, frequency of administration, and out-of-pocket cost) and their levels were used to develop a discrete choice experiment questionnaire. Each questionnaire comprised seven choice sets and each choice set contained two hypothetical DMTs and an opt-out alternative. A total of 1,200 U.S. patients with MS were asked to choose a DMT option or opt-out in each choice set. Multinomial logit model was used to determine relative preferences of each attribute. WTPs for all attributes and DMTs were calculated. ResultsA total of 508 patients were analyzed. Patients preferred DMTs with lower relapse rate, lower disability progression, lower severe adverse event, lower frequency of administration, and lower cost. In addition, they preferred oral DMTs. They were willing to pay $2,768, $289, $292, and $76 a month in exchange for every 1-time decrease in the number of relapses in two years, every 1% decrease in disability progression in two years, every 1% decrease in severe adverse events, and every 1-time decrease in the frequency of administration per month, respectively. The patients were willing to pay, in relation to market prices, between $7,020 and $134,934 per year for all DMTs, but interferon beta-1a SC. ConclusionsPatients with MS considered relapse rate, disability progression, severe adverse events, route of administration, frequency of administration, and out-of-pocket cost, when they chose DMTs. Their WTPs for DMTs varied widely.

Teriflunomide: A Review in Relapsing–Remitting Multiple Sclerosis

Teriflunomide (Aubagio®) is a disease-modifying immunomodulatory drug with anti-inflammatory properties that selectively and reversibly inhibits the mitochondrial enzyme dihydro-orotate dehydrogenase, with consequent inhibition of de novo pyrimidine synthesis and reduced lymphocyte proliferation. Based on extensive evidence from randomized controlled trials (RCTs) and the real-world setting, oral teriflunomide is an effective and generally well tolerated treatment in patients with relapsing multiple sclerosis (MS), with these benefits maintained during long-term treatment (≥ 10years) and no new safety signals identified. In pivotal RCTs in this patient population, teriflunomide provided significantly better efficacy than placebo (TEMSO and TOWER) and was as effective as interferon β-1a (TENERE) in terms of improvements in clinical outcomes (such as reduced annualized relapse rates, prevention of disability progression) and/or MRI-assessed disease activity measures. Albeit head-to-head trials would definitively establish the relative efficacy of oral disease-modifying therapies, given its convenient oral regimen and beneficial effects in reducing relapses and disease activity, teriflunomide remains an effective option for the management of relapsing-remitting MS (RRMS).

Persistence and adherence to the new oral disease-modifying therapies for multiple sclerosis: A population-based study

ObjectiveTo examine persistence and adherence to the oral disease-modifying therapies (DMTs) for multiple sclerosis (MS). MethodsPopulation-based health administrative databases in British Columbia, Canada were accessed to identify all individuals filling an oral DMT prescription for MS (fingolimod, dimethyl fumarate, teriflunomide) between January 2011 and December 2015. Predictors of persistence and adherence at 6 and 12 months were assessed using logistic regression, with estimates expressed as adjusted odds ratios (aORs), and 95% confidence intervals (CIs). ResultsOf 858 individuals with ≥6 months of follow-up, the mean age at first prescription was 43.0 (SD:10.3) years; 74.2% were women. By 6 months 11.0% (94/858) had discontinued their initial oral DMT; by 12 months the proportion was 19.6% (113/577). Over 6 and 12 months, among those persisting with their oral DMT, 82.5% (630/764) and 81.7% (379/464) exhibited optimal adherence (proportion of days covered ≥80%). Age, sex, calendar year and comorbidity were not associated with persistence or adherence. Individuals with higher neighbourhood-level socioeconomic status had higher odds of discontinuation within 6 months (aOR = 2.2; 95%CI:1.3–3.7). Those who had previously used another DMT had higher odds of optimal adherence (6 months aOR = 2.4;95%CI:1.6–3.6, and 12 months aOR = 2.4; 95%CI:1.5–3.9). ConclusionApproximately 1 in 10 individuals discontinued their first oral DMT within 6 months, and 1 in 5 did so within one year. However, among those who did continue drug, a high proportion (>80%) exhibited optimal adherence. Predictors of persistence or adherence with immediate practical application were lacking; this highlights the challenges in optimizing drug therapy.