Injectable Disease-modifying Therapies Research Articles

Impact of discontinuing disease-modifying therapies on health care utilization among midlife patients with multiple sclerosis in the United States.

Multiple sclerosis (MS) is a lifelong progressive neurological disease treated primarily with disease-modifying therapies (DMTs). Disease activity tends to decline as patients age. Midlife represents a crossroads where the risks of DMT may outweigh the benefits, prompting providers to consider DMT discontinuation to reduce treatment burden. However, real-world evidence on the impact of DMT discontinuation among midlife patients is lacking. To evaluate the association between DMT discontinuation and health care utilization among midlife patients with MS. Midlife patients with MS who received an injectable or oral DMT between 2001 and 2018 were identified from the MarketScan commercial claims database. DMT discontinuation, defined as a treatment gap exceeding 90 days in days supply, was the independent variable. Patients who discontinued DMTs had their index date set as the last gap day, whereas index dates for those who continued DMTs were matched based on the time distribution of index dates of discontinuers. Inpatient hospitalizations (all-cause, MS-related, and non-MS-related), emergency department (ED) visits (all-cause, MS-related, and non-MS-related), and relapse-related hospitalizations and outpatient visits were independently evaluated during the 365-day follow-up. Patients were observed until the occurrence of an event (depending on the model), deviation from the treatment group, disenrollment, death, end of follow-up, or data unavailability. Stabilized inverse probability of treatment weighting (sIPTW) was employed to balance the 2 groups. The associations between DMT discontinuation and each utilization outcome were estimated using Cox proportional hazard regression models with sIPTW. Of 149,721 midlife patients with MS, 22.8% discontinued DMTs and 77.2% continued DMTs. Patients who discontinued DMTs had a higher cumulative incidence for all utilization outcomes during the 365-day follow-up than those who continued DMTs. Cox regression showed that DMT discontinuation was associated with a 10.3% and 24.9% higher rate of all-cause and non-MS-related inpatient hospitalizations, respectively, with no significant association found for MS-related hospitalizations. Patients discontinuing DMTs exhibited higher utilization rates for ED visits, with an increase of 21.3% for all-cause, 23.0% for MS-related, and 20.9% for non-MS-related visits compared with those who continued DMTs. We also observed a 15.9% and 52.1% higher rate of relapse-related hospitalizations and outpatient visits associated with DMT discontinuation, respectively. This study revealed that DMT discontinuation was associated with higher health care services utilization among midlife patients with MS, especially relapse-related outpatient visits. DMT discontinuation during midlife may be premature, and DMTs may still be necessary to reduce health care utilization.

As time goes by: Treatment challenges in elderly people with multiple sclerosis

A demographic shift in multiple sclerosis (MS) is leading to an increased number of elderly people with MS (pwMS) and a rise in late-onset MS (LOMS) cases. This shift adds complexity to the treatment management of these patients, due to enhanced treatment-associated risks and the possible interplay between immunosenescence and disease-modifying therapies (DMTs).In the present paper, we performed a systematic review of the current evidence concerning the relationship between aging and treatment management in elderly pwMS. Our literature search identified 35 original studies relevant to this topic.The gathered evidence consistently indicates a diminished efficacy of DMTs in older pwMS, particularly in preventing disability accrual. Against this background, high-efficacy therapies (HETs) appear to show less benefit over moderate-low-efficacy DMTs in older patients. These data mainly derive from observational retrospective studies or meta-analyses conducted on randomized clinical trials (RCTs). RCTs, however, exclude pwMS older than 55 years, limiting our ability to acquire robust evidence regarding this patient group.Regarding treatment discontinuation in elderly pwMS with stable disease, the available data, which mainly focuses on older injectable DMTs, suggests that their suspension appears to be relatively safe in terms of disease activity. Nevertheless, the first RCT specifically targeting treatment discontinuation recently failed to demonstrate the non-inferiority of treatment discontinuation over continuation, in terms of MRI activity. On the other hand, the evidence on the impact of discontinuation on disease progression is more conflicting and less robust. Furthermore, there is an important lack of studies concerning sequestering DMTs and virtually no data on the discontinuation of anti-CD20 monoclonal antibodies.De-escalation strategy is gaining attention as a de-risking approach alternative to complete treatment discontinuation. It may be defined as the decision to shift from HETs to less potent DMTs in elderly pwMS who have a stable disease. This strategy could reduce treatment-related risks, while minimizing the risk of disease activity and progression potentially associated with treatment discontinuation. This approach, however, remains unexplored due to a lack of studies.Given these findings, the present scenario underlines the urgent need for more comprehensive and robust studies to develop optimized, data-driven treatment strategies for elderly pwMS and LOMS, addressing the unique challenges of MS treatment and aging.

Comparative Effectiveness of Natalizumab, Fingolimod, and Injectable Therapies in Pediatric-Onset Multiple Sclerosis: A Registry-Based Study.

Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses, and though patients with POMS usually recover from relapses better than adults, patients with POMS reach irreversible disability at a younger age than adult-onset patients. There have been few randomized, placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021. Patients were matched using inverse probability treatment weighting. The primary outcome was time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. A total of 1,218 patients with POMS were included in this analysis. Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMTs (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; p = 0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMTs (HR, 0.15; 95% CI 0.07-0.31; p < 0.001) or fingolimod (HR, 0.37; 95% CI 0.14-1.00; p = 0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting-adjusted patient populations were confirmed in multiple sensitivity analyses. Our analyses of relapse risk suggest that natalizumab is more effective than fingolimod in the control of relapses in this population with high rates of new inflammatory activity, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. In addition, both fingolimod and natalizumab were more effective than first-line injectable therapies. This study provides Class II evidence that patients with POMS treated with natalizumab had a lower risk of relapse than those with fingolimod.

Navigating the discontinuation of multiple sclerosis first line treatments: A paradigm shift in patient care

BackgroundThis retrospective study, conducted between 2005 and 2016, investigated the outcomes of patients with multiple sclerosis (MS) who discontinued injectable first-line disease-modifying therapies (DMTs). The study aimed to identify factors influencing treatment discontinuation and assess the impact of discontinuation on disease progression. MethodsData was collected from 2,270 patients who received injectable DMTs for at least two years and subsequently discontinued treatment due to clinical and MRI remission, side effects, or noncompliance. Patients were categorized into two groups: those stable after discontinuation (SAD) and those with relapse after discontinuation (RAD). Survival analysis and logistic regression were employed to assess factors influencing treatment discontinuation. ResultsOf the 60 patients who discontinued DMTs, one-third (n = 20) remained stable, while 40 patients experienced clinical and/or MRI activity during follow-up. The SAD group had a significantly later age at treatment discontinuation compared to RAD patients (35.9 ± 11.1 vs. 30.7 ± 6.1, p = 0.025). Patients below 40 years old had a higher likelihood of experiencing worsening (75 %), while those over 50 years old demonstrated an 80 % stability rate. SAD patients used DMTs for a more extended period than RAD patients (69.1 ± 47.3 vs. 46.6 ± 20.3 months, p = 0.012). A notable proportion (42.9 %) of worsened patients discontinued DMTs without consulting a physician, emphasizing potential challenges in treatment adherence. After treatment discontinuation, RAD patients experienced relapses after a median of 21.0 months. Survival analysis suggested a more favorable disease course for patients who discontinued treatment after achieving a stable period (p = 0.237), with evidence of differentiation between groups after four years. Regression analysis indicated that older age at discontinuation had a favorable impact on relapse probability (HR: 0.904; p = 0.031; 95 % CI: 0.825, 0.991). Reasons for discontinuation unrelated to disease stability showed a positive but imprecise effect on relapse probability. ConclusionThis study provides insights into the outcomes of MS patients discontinuing injectable DMTs, emphasizing the importance of age at discontinuation and reasons for treatment cessation in predicting disease progression. The findings suggest that discontinuation after achieving stability may lead to more favorable outcomes, highlighting the need for personalized treatment decisions in MS management. Further research is warranted to validate these findings and inform clinical practices.

Utilization of peginterferon-β-1a in the real-world practice for relapsing-remitting multiple sclerosis.

Peginterferon β-1a (PEG-IFN-β-1a) is the most recent interferon beta formulation approved for treating relapsing-remitting multiple sclerosis (RRMS). We aim to describe the real-world utilization of PEG-IFN-β-1a in RRMS and compare it with other injectable disease-modifying therapies (DMTs). In this population-based study, we used 2015-2019 routinely collected healthcare data of the Campania region of Italy from National Healthcare System DMT prescriptions, inpatient and outpatient clinical records of hospitals in Campania, and the Federico II University MS clinical registry for a subset of patients. We included individuals with RRMS receiving new prescriptions of PEG-IFN-β-1a [n=281; age = 38.8±12.3 years; females=70.5%; disease duration = 8.4±8.3 years; Expanded Disability Status Scale (EDSS) at baseline=2.0 (1.0-6.5)], glatiramer acetate [n=751; age = 46.0±11.4 years; females=67.1%; disease duration = 9.8±8.2 years; EDSS=4.0 (1.5-8.5)], and subcutaneous (SC) IFN-β-1a [n=1,226; age = 39.7±11.7 years; females=66.5%; disease duration = 8.2±6.5 years; EDSS 2.5 (1.5-6.5)]. Adherence [medication possession ratio (MPR)], escalation to more effective DMTs, hospitalization rates and costs were measured. We used mixed-effect linear regression models (for adherence, hospitalization rates and costs) and Cox regression models (for escalation) to assess differences between PEG-IFN-β-1a (statistical reference), glatiramer acetate, and SC IFN-β-1a. All models included age, sex, previous treatment/untreated, year of treatment initiation, treatment duration, and adherence as covariates. Adherence was lower in glatiramer acetate (MPR = 0.91±0.1; Coeff=-0.11; p<0.01), and IFN-β-1a (MPR = 0.92±0.1; Coeff=-0.08; p<0.01), compared with PEG-IFN-β-1a (MPR = 1.01±0.1). The probability of escalating to more effective DMTs was higher for glatiramer acetate (14.9%; HR=4.09; p<0.01) and IFN-β-1a (9.1%; HR=3.35; p=0.01), compared with PEG-IFN-β-1a (4.9%). No differences in annualized hospitalization rates were identified between glatiramer acetate [annualized hospitalization rates (AHR) = 0.05±0.30; Coeff=0.02; p=0.31), IFN-β-1a (AHR = 0.02±0.21; Coeff=0.01; p=0.97], and PEG-IFN-β-1a (AHR = 0.02±0.24); however, monthly costs for MS admissions were higher for glatiramer acetate (€49.45±€195.27; Coeff=-29.89; p=0.03), compared with IFN-β-1a (€29.42±€47.83; Coeff=6.79; p=0.61), and PEG-IFN-β-1a (€23.91±€43.90). SC PEG-IFN-β-1a and IFN-β-1a were used in relatively similar populations, while glatiramer acetate was preferred in older and more disabled patients. PEG-IFN-β-1a was associated with higher adherence and lower escalation rates toward more effective (and costly) DMTs.

Final results of the PANGAEA 2.0 study: Treatment benefits of fingolimod for active RRMS patients switching from other DMTs (P6-3.009)

<h3>Objective:</h3> The aim of the PANGAEA 2.0 study was to investigate the efficacy and long-term benefits (3 years) of fingolimod in relapsing-remitting multiple sclerosis (RRMS) patients with disease activity switching from other disease-modifying therapies (DMTs). <h3>Background:</h3> In the treatment of RRMS, individualized sequential therapies can be used to optimize the outcome. It is, however, necessary to understand the efficacy and overall impact of sequential switching. <h3>Design/Methods:</h3> The non-interventional, real-world evidence study included 2,579 disease-active RRMS-patients treated with fingolimod at 240 neurological practices and clinics in Germany out of which 966 completed the study. The patients, who were either untreated or treated with an approved DMT other than fingolimod before study start, were observed for 3 years. To obtain insight into the effectiveness of changing to fingolimod, subgroup analyses were based on the patients’ last therapy before switching: oral DMT (oDMT; dimethyl fumarate, teriflunomide), injectable DMT (iDMT; interferons, glatiramer acetate), natalizumab, other DMTs and treatment-naive. <h3>Results:</h3> At baseline, the patient population was mostly female (71.1%) and patients were on average 39.2 (±10.8) years old. The majority of patients had received only 1 treatment prior to study start. In total, 1,138 patients had received an iDMT as last therapy before receiving fingolimod. On average, patients presented with an EDSS of 2.4±1.5 at study start. Over 3 years, the mean EDSS total score remained on a relatively stable level in the subgroups iDMT (EDSS: 2.4±1.6) and oDMT (EDSS: 2.6±1.5). The EDSS increased slightly in the group who was previously on natalizumab treatment (EDSS: 3.3±1.6) along with a slight increase in FSMC. The mean SDMT remained on a stable level in all subgroups. <h3>Conclusions:</h3> PANGAEA 2.0 brings us real-world insights into the effectiveness of fingolimod in disease-active RRMS-patients. The results show that the disease burden remained relatively stable during 3 years on fingolimod, regardless of the previous therapy. <b>Disclosure:</b> Dr. Weiss has received personal compensation for serving as an employee of Novartis Pharma GmbH. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS Celgene. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Ziemssen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for BMS Celgene. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. The institution of Dr. Ziemssen has received research support from Biogen. The institution of Dr. Ziemssen has received research support from Novartis. The institution of Dr. Ziemssen has received research support from Merck. The institution of Dr. Ziemssen has received research support from Sanofi. The institution of Dr. Ziemssen has received research support from Celgene.

Real-world effectiveness of switching treatment after initial platform injectable disease-modifying therapies in pediatric multiple sclerosis in the US (P14-3.008)

Real-world effectiveness of switching treatment after initial platform injectable disease-modifying therapies in pediatric multiple sclerosis in the US (P14-3.008)

Severity and worsening of fatigue among individuals with multiple sclerosis.

Fatigue is associated with reduced quality of life and social participation, and poor employment outcomes. However, most studies examining fatigue are limited by small sample sizes or short follow-up periods. To characterize the natural history of fatigue. The North American Research Committee on Multiple Sclerosis Registry participants with ≥7 years of longitudinal data between 2004 and 2019 and a relapsing disease course were included. A subset of participants enrolled within 5 years of diagnosis was identified. The Fatigue Performance Scale assessed fatigue and ≥1-point increase in Fatigue Performance Scale sustained at the next survey defined fatigue worsening. Of 3057 participants with longitudinal data, 944 were within 5 years of multiple sclerosis diagnosis. Most participants (52%) reported fatigue worsening during follow-up. Median time to fatigue worsening ranged from 3.5 to 5 years at lower levels of index fatigue. Fatigue worsening was associated with lower annual income, increasing disability, lower initial fatigue level, taking injectable disease-modifying therapies and increasing depression levels in the relapsing multiple sclerosis participants. Most multiple sclerosis participants early in their disease suffer from fatigue and at least half reported fatigue worsening over time. Understanding factors associated with fatigue may help to identify populations most at risk of fatigue worsening will be informative for the overall management of patients with multiple sclerosis.

Disease-Modifying Therapy in Multiple Sclerosis: Evaluation of Patients Satisfaction in Iranian Multiple Sclerosis Population.

Medication satisfaction is a patient-reported outcome which could show medication adherence. The aim of this study was to determine Iranian MS patients' satisfaction with Disease Modifying Therapies (DMTs). A standardized questionnaire was developed using Treatment Satisfaction Questionnaire for Medication (TSQM). The online link was released on IMSS (Iranian Multiple Sclerosis Society) social media channel, accessible to 4272 MS patients totally. Three hundred and ninety-four patients participated in our survey with 324 females, 70 males and an F/M ratio of 4.6:1. The most frequent DMTs used were interferon-beta (IFNβ) followed by rituximab. The mean effectiveness and global satisfaction scores were significantly higher for injectable DMTs, while the convenience score was significantly higher for oral DMTs. Mean effectiveness and side-effect scores were significantly higher in the Tysabri group and convenience score was significantly higher in the fingolimod group while global satisfaction was higher in the IFNβ group. The global satisfaction and effectiveness were significantly higher with injectable DMTs while the convenience score was significantly higher with oral DMTs.

Adverse Obstetric Outcomes in Pregnant Women Using Natalizumab for the Treatment of Multiple Sclerosis: A Systematic Review.

Multiple sclerosis is a common disease in women of childbearing age, characterized by demyelination of the central nervous system. Among the different treatment options available, disease-modifying therapies (DMTs) are the most efficacious, and natalizumab (NAT) is an injectable DMT best for relapsing-remitting multiple sclerosis. However, it comes under pregnancy category C drug classification. This systematic review aims to analyze the adverse outcomes of using NAT during pregnancy. PubMed/Medline, PubMed Central (PMC), ScienceDirect, and Google Scholar were the databases used to search for articles. Appropriate keywords and Medical Subject Headings (MeSH) strategy were used to identify relevant articles. Articles were then screened using inclusion/exclusion criteria followed by the title and abstract screening. The Joanna Briggs Institute (JBI) quality appraisal tools were used for quality check, and nine articles were finalized for review. NAT suspension during pregnancy is shown to have a high risk of disease relapse. Despite the risk of mild hematological abnormalities in the newborn and the risk of spontaneous abortions at the same rate as that of the general population, NAT use can be considered safe in pregnancy. These adverse outcomes can be minimized by strict monitoring of patients. Studies of better quality with larger sample sizes are needed for further investigation.

Treatment satisfaction in patients with relapsing-remitting multiple sclerosis initiated on teriflunomide in routine clinical practice: Australian observational data

BackgroundAdherence and persistence are critical to optimising therapeutic benefit from disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS). This prospective, open-label, multicentre, observational study (AubPRO), conducted in 13 hospital-based neurology...

Trends in disease-modifying therapy use in patients with multiple sclerosis using a 10-year population-based cohort study in France

ABSTRACT Background The availability of new disease-modifying therapies (DMTs) for patients with multiple sclerosis (MS) provides an opportunity for improving outcomes but makes disease management more complex. Our study aimed to describe changes in therapeutic practices over the period 2009–2018 and measure the impact of the arrival of oral DMTs on the use of injectable DMTs. Methods Data were extracted from a representative 1/97 sample of the French population covered by the healthcare insurance system. Study period was set from 1 January 2009 to 31 December 2018. Four periods of MS identification were defined (before 2009, 2009–2011, 2012–2015, and 2016–2018). Results Overall, 1,508 patients with MS were included, of whom 876 (58.1%) were treated at least once over the study period. Untreated patients were older and had more comorbidities than treated ones. First-line DMTs were the most frequent initial DMT (78.5%), and a shift has operated from injectable to oral drugs over time. The proportion of patients receiving several DMTs increased with the number of available drugs. End 2018, relative parts of all DMTs were almost equal. Conclusions This study provides valuable insights into the real-world use of DMTs and changes that have operated over time.

Real-world disease-modifying therapy usage in persons with relapsing-remitting multiple sclerosis: Cross-sectional data from the Swiss Multiple Sclerosis Registry

IntroductionSeveral disease-modifying therapies (DMTs), covering a broad spectrum of mechanisms of action, have been approved by regulatory agencies for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, only little is known about the current real-world treatment situation in Switzerland. Based on data from a diverse population of 668 persons with RRMS from the Swiss Multiple Sclerosis Registry (SMSR), the present study aims to fill this gap with a descriptive, cross-sectional approach. MethodsData originated from the SMSR baseline questionnaire and follow-up surveys. Data on current health status and life situation in the last 6 months were extracted from the survey distributed throughout 2020 and 2021, while data on disease-modifying therapy (DMT) histories were included from preceding surveys. Initially, data was stratified into three DMT groups according to the current DMT status (NO (No DMT), CONTINUED (DMT started more than 6 months ago), and NEW (DMT started less than 6 months ago)). In a subsequent analysis, the sample was stratified into groups corresponding to the five most frequently prescribed DMTs. Self-reported outcomes including therapy discontinuation or interruption, relapses and side-effects in the last 6 months were analyzed per group. Life and health situation parameters were also determined and analyzed. ResultsThe study population consisted of 445 (66.6%) individuals belonging to the CONTINUED, 84 (12.6%) to the NEW, and 139 (20.8%) to the NO group. Within the NO group, 24 (17.3%) reported relapses. Furthermore, self-reported relapses (28 (33.3%)), side-effects (39 (46.4%)), and treatment discontinuations or interruptions (30 (35.7%)) occurred more frequently in the NEW compared to the CONTINUED group (37 (8.3%), 125 (28.1%), 8 (1.8%), respectively). The three groups also differed with respect to age, time since diagnosis, number of symptoms, DMT history, and health-related quality of life. The five most frequently prescribed DMTs included fingolimod (33.4%), dimethyl fumarate (25.0%), ocrelizumab (23.6%), natalizumab (10.6%) and teriflunomide (7.5%). The frequency of self-reported relapses ranged from 9.7% to 13.6%. Notable differences were found in the number of self-reported side-effects, ranging from 9.1% with natalizumab to 56.7% with dimethyl fumarate. DiscussionThis cross-sectional analysis suggested that the majority of individuals with RRMS in Switzerland continuously receive tolerable DMT. However, groups not receiving DMT or struggling with side-effects or continued disease worsening while on DMT still persist. It is conceivable that the number of self-reported symptoms indicates the need for more detailed clarification of the DMT characteristics and expectations of treatment outcomes. Injectable DMTs no longer play a major role in the treatment of RRMS in Switzerland and a trend toward an early use of potent drugs is emerging.

Trends in the use of disease-modifying therapies among reproductive-aged women with multiple sclerosis in the United States from 2010 to 2019.

Multiple sclerosis (MS) is a chronic disease of the central nervous system that disproportionately affects women, with typical onset during reproductive age. Several disease-modifying therapies (DMTs) are FDA-approved to slow disease progression, but are not indicated for use during pregnancy. Our objective was to describe trends over time (2010-2019) in monthly point prevalence of DMT use among reproductive-age women, overall and by generic name. This study used administrative claims data from the US during 2009-2019 to identify women age 15-44 with MS and continuous insurance coverage for ≥12 months. DMTs were identified using prescription fills and procedural claims for alemtuzumab, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, mitoxantrone, natalizumab, ocrelizumab, and teriflunomide. Monthly prevalent use was defined as ≥1 days' supply of a DMT in the month. Age- and region-standardized monthly prevalence was estimated nonparametrically. Among 42 281 reproductive-aged women over 818 179 person-months, DMT use increased from a minimum monthly prevalence of 49.3% (February, 2011) to a maximum of 58.7% (April, 2019). In 2010, prevalence of injectable DMTs was 43.1% compared to 2.5% for oral DMTs; by 2014, however, oral DMTs (26.5%) surpassed injectable DMTs (23.7%) as the most common route of administration. In the most recent data available (December, 2019), the most common DMTs were dimethyl fumarate, glatiramer acetate, and fingolimod. DMT use among reproductive-aged women has rapidly evolved during the past decade. Collaborative treatment decision making between women with MS and clinicians may help optimize MS care and improve DMT uptake during reproductive years.

POSA61 Incremental Cost per Relapse Avoided of Ozanimod Compared with First-Line Disease-Modifying Therapies for Relapsing Forms of Multiple Sclerosis

Number-needed-to-treat (NNT) and cost data were combined to assess the cost-effectiveness of branded disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS), and compare the incremental healthcare costs per relapse avoided and healthcare cost savings of ozanimod with commonly used oral and injectable DMTs.

Objective medication adherence and persistence in people with multiple sclerosis: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Medication adherence is critical for the realization of pharmacotherapy benefits and reduced healthcare expenditure. Studies have shown up to 60% of people with Multiple sclerosis (MS) experience suboptimal medication adherence, which is associated with poorer health outcomes and subsequent discontinuation. The current systematic review reported on objectively measured adherence and discontinuation rates for self-administered oral and injectable disease-modifying therapies (DMTs). OBJECTIVES: To identify whether, in people with MS, the introduction of oral DMTs has improved medication adherence when compared with injectable DMTs. The secondary aim was to report synthesized objectively measured medication adherence and persistence rates for both oral and injectable DMTs in MS across varying study durations. METHODS: Literature searches were conducted through PubMed, Web of Science, Scopus, and PsycINFO. Inclusion criteria were limited to English, peer-reviewed, objective, self-administered DMT articles, published between July 1993 to December 2019. Publications reporting combined intravenous and self-administered DMT data, or that did not account for DMT switching in discontinuation rates, were excluded. Data were synthesized into observation lengths ranging from less than 8 months to greater than 36 months. Meta-analysis and meta-regression were undertaken on both oral and injectable 12-month adherence and discontinuation data. RESULTS: In total, 61 articles were included; 46 articles examined adherence and 26 examined discontinuation. Twelve-month adherence ranged between 53.0% to 89.2% for oral (N = 7) and 47.0% to 77.4% for injectable DMTs (N = 7). Results from the meta-analysis and meta-regression show significantly higher pooled mean medication possession ratio (MPR) adherence for oral DMTs (91.0%) when compared to injectable DMTs (77.0%) over 12 months (β = -0.146; 95% CI: -0.263 to -0.029). Results indicate major asymmetry across studies (LFK index: -5.18), proposing the presence of significant publication bias. Mean discontinuation over 12 months was between 10.5% to 33.3% for oral (N = 7) and 15.2% to 50.8% for injectable DMTs (N = 10), with meta-analysis results indicating the presence of significant heterogeneity (I2 Injectable: 99.5%; I2 Oral: 93.1%) between studies included in each subgroup. However, no appreciable difference in mean discontinuation rates across groups (Injectable: 27%; 95% Cl: 19.0%-34.0%; Oral: 24%; 95% CI: 17.0%-31.0%) was found. CONCLUSIONS: Medication adherence for oral DMTs suggests a significant improvement compared to adherence for injectable DMTs. No significant difference in discontinuation rates between oral and injectable DMTs was found. Oral DMT adherence and persistence studies are limited, given their relatively recent introduction. Suboptimal medication adherence and discontinuation issues remain present for both oral and injectable DMTs. Future studies would benefit from improved consistency in methodology, such as comparable adherence and persistence definitions. DISCLOSURES: The authors did not receive any funding for this study. Mardan and Hussain have nothing to disclose. Grech reports grants from Merck Pharmaceutical, outside the submitted work. Allan reports grants received from Merck Pharmaceutical outside the submitted work. Allan holds advisory board and consulting positions with Merck and advisory board positions for Bristol Myers Squibb and Novartis, for which Monash Institute of Neurological Diseases receives consulting fees.

Impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany between 2010 and 2018: real-world data from the German NeuroTransData multiple sclerosis registry

ObjectiveTo evaluate the impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany.DesignThis study employs real-world data captured in-time during clinical visits in 67 German neurology...

First-line therapies in late-onset multiple sclerosis: An Italian registry study.

Background and purposeThe diagnosis of late‐onset (age ≥50 years old) relapsing remitting multiple sclerosis (LORRMS) has been increasingly described in clinical practice, whereas data focusing on the specific therapeutic management of LORRMS are scarce. Our objective was to compare the effectiveness of injectable and oral first‐line disease‐modifying therapies (DMTs) in a cohort of LORRMS patients with time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation.MethodsThis is a multicenter, observational, retrospectively acquired cohort study on LORRMS‐naïve patients from the Italian MS Register who started either injectable or oral first‐line DMTs between January 1, 2013 and December 31, 2017. LORRMS patients were divided into two groups, namely the injectable group (IG) and oral group (OG). Cox models adjusted with inverse probability‐weighted propensity score were built for the investigated outcomes.ResultsOf a cohort of 3989 patients, 302 were enrolled (203 in the IG and 99 in the OG). The two cohorts did not differ in baseline characteristics. Time to first relapse did not show any difference between the two groups (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 0.50–2.46, p = 0.797). Furthermore, no differences were found between the two groups with respect to the risk of CDP (HR: 1.04; 95% CI: 0.35–3.06, p = 0.939), nor for the risk of DMT discontinuation (HR: 0.90; 95% CI: 0.17–2.08, p = 0.425).ConclusionsReal‐world data from the Italian MS Register suggested that both injectables and oral first‐line DMTs similarly controlled the investigated outcomes in LORRMS.

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

BackgroundReal-world studies of disease-modifying therapies (DMTs) in multiple sclerosis (MS) have reported suboptimal adherence.ObjectiveWe aimed to describe treatment patterns, relapses, healthcare resource utilization, and costs in MS patients experiencing their first observed DMT switch.MethodsIn this retrospective, claims database study, adult patients were selected if they had an MS diagnosis and DMT claim during the study period (1 January 2009–31 March 2019). Patients who switched to a new DMT between 1 January 2010 and 31 March 2018 were included. Adherence, persistence, relapses, and all-cause and MS-related healthcare utilization and costs were reported pre- and post-index.ResultsIn total, 1554 MS patients were identified; the mean age was 46 years and most (74%) were female. The majority of patients switched from an injectable DMT (n = 1116; 71.8%), and patients generally switched to an oral DMT (n = 878; 57%). Among patients who switched DMTs, 46.0% (n = 715) were nonadherent, 42% (n = 645) were nonpersistent, and 21.5% (n = 334) relapsed in the 12 months post-switch. An increase in all-cause and MS-related healthcare costs was observed pre- to post-index for all patients. Cost drivers included outpatient visit costs and pharmacy prescriptions. Compared with patients who switched to an injectable DMT, those who switched to an oral DMT had significantly higher persistence and adherence. No significant difference was observed in post-index relapse or all-cause and MS-related total cost of care.ConclusionLow adherence and poor persistence remain following an initial DMT switch; however, patients who switched to oral DMTs had higher persistence and adherence.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00251-w.

Early Aggressive Treatment Approaches for Multiple Sclerosis.

Purpose of reviewThis review presents a comprehensive analysis of the current high-efficacy disease-modifying therapies (DMTs) available for treatment of multiple sclerosis (MS). We discuss the existing approved and emerging therapeutics in patients with relapsing and progressive forms of MS using data from clinical trials and observational studies. Treatment considerations in pediatric and pregnant populations are also reviewed. Finally, we discuss the treatment paradigms of the escalation and early aggressive approaches to treatment of MS, with review of ongoing clinical trials to compare these approaches.Recent findingsNatalizumab has shown promising data on efficacy in not only randomized trials but also observational studies when compared with placebo, the injectable DMTs, and fingolimod. The anti-CD20 B cell depleting therapies (rituximab, ocrelizumab, and ofatumumab) have also demonstrated superiority in randomized clinical trials compared to their comparator group (placebo, interferon, and teriflunomide, respectively) and rituximab has shown in observational studies to be more effective than older injectable therapies and some of the oral therapies. Alemtuzumab has shown good efficacy in randomized controlled trials and observational studies yet has several potentially severe side effects limiting its use. Mitoxantrone has similarly demonstrated significant reduction in new disease activity compared to placebo but is rarely used due to its severe side effects. Cladribine is an oral DMT often grouped in discussion with other higher efficacy DMTs but may be slightly less effective than the other therapies described in this review. Many emerging targets for therapeutic intervention are currently under investigation that may prove to be beneficial in early aggressive MS, including autologous hematopoietic stem cell transplantation.SummaryTraditionally, MS has been treated with an escalation approach, starting patients on a modestly effective DMT and subsequently escalating to a higher efficacy DMT when there is evidence of clinical and/or radiologic breakthrough activity. With the development of higher efficacy therapies and emerging data showing the potential positive long-term impact of these therapies when started earlier in the disease course, many clinicians have shifted to an early aggressive treatment approach in which patients are initially started on a higher efficacy DMT. Two clinical trials, the TRaditional versus Early Aggressive Therapy for MS (TREAT-MS) trial and the Determining the Effectiveness of earLy Intensive Versus Escalation approaches for the treatment of Relapsing-remitting MS (DELIVER-MS) trial, aim to directly compare these treatment strategies and their impact on clinical and radiologic outcomes.