Oral Disease-modifying Therapies Research Articles

Prediction of disease activity and treatment failure in relapsing–remitting MS patients initiating daily oral DMTs

Background: Limited data exist regarding treatment response prediction to oral disease-modifying therapies (DMTs) in multiple sclerosis (MS). Objectives: We assessed the capacity of available scoring systems to anticipate disease activity parameters in naïve relapsing–remitting MS (RRMS) patients initiating daily oral DMTs, hypothesizing that they exhibit different predictive potentials. Methods: We conducted a retrospective study and applied the Rio Score (RS), modified Rio Score (mRS), and MAGNIMS Score 12 months after DMT initiation. At 36 months, we examined their ability to predict evidence of disease activity (EDA) components and treatment failure by logistic regression analysis. Results: Notably, 218 patients (62.4% females) initiating dimethyl fumarate, teriflunomide, and fingolimod were included. At 36 months, the RS high-risk group predicted evidence of clinical activity (odds ratio (OR) 10 [2.7–36.9]) and treatment failure (OR 10.6 [3.4–32.5]) but did not predict radiological activity (OR 1.9 [0.7–5]). The mRS non-responders group did not predict EDA and treatment failure. RS, mRS, and MAGNIMS 0 categories showed significantly lower EDA and treatment failure than the remainder. Conclusion: Scoring systems present different predictive abilities for disease activity parameters at 36 months in MS patients initiating daily oral therapies, warranting further adjustments (i.e. introduction of fluid biomarkers) to depict disease activity status fully.

Comparative efficacy of ofatumumab versus oral therapies for relapsing multiple sclerosis patients using propensity score analyses and simulated treatment comparisons.

Evidence from network meta-analyses (NMAs) and real-world propensity score (PS) analyses suggest monoclonal antibodies (mAbs) offer a therapeutic advantage over currently available oral therapies and, therefore, warrant consideration as a distinct group of high-efficacy disease-modifying therapies (DMTs) for patients with relapsing multiple sclerosis (RMS). This is counter to the current perception of these therapies by some stakeholders, including payers. A multifaceted indirect treatment comparison (ITC) approach was undertaken to clarify the relative efficacy of mAbs and oral therapies. Two ITC methods that use individual patient data (IPD) to adjust for between-trial differences, PS analyses and simulated treatment comparisons (STCs), were used to compare the mAb ofatumumab versus the oral therapies cladribine, fingolimod, and ozanimod. As IPD were available for trials of ofatumumab and fingolimod, PS analyses were conducted. Given summary-level data were available for cladribine, fingolimod, and ozanimod trials, STCs were conducted between ofatumumab and each of these oral therapies. Three efficacy outcomes were compared: annualized relapse rate (ARR), 3-month confirmed disability progression (3mCDP), and 6-month CDP (6mCDP). The PS analyses demonstrated ofatumumab was statistically superior to fingolimod for ARR and time to 3mCDP but not time to 6mCDP. In STCs, ofatumumab was statistically superior in reducing ARR and decreasing the proportion of patients with 3mCDP compared with cladribine, fingolimod, and ozanimod and in decreasing the proportion with 6mCP compared with fingolimod and ozanimod. These findings were largely consistent with recently published NMAs that identified mAb therapies as the most efficacious DMTs for RMS. Complementary ITC methods showed ofatumumab was superior to cladribine, fingolimod, and ozanimod in lowering relapse rates and delaying disability progression among patients with RMS. Our study supports the therapeutic superiority of mAbs over currently available oral DMTs for RMS and the delineation of mAbs as high-efficacy therapies.

Quantifying the administration and monitoring time burden of several disease-modifying therapies for relapsing multiple sclerosis in the United Kingdom: A time and motion study

BackgroundThe treatment landscape for relapsing multiple sclerosis (MS) has changed dramatically in recent decades, including an increasing number of high-efficacy disease-modifying therapies (DMTs) with varied administration and monitoring requirements. Coupled with greater focus on earlier treatment, these factors have resulted in stretching of the capacity of MS specialist services and allied healthcare professionals (HCPs). To assist with the effective planning of MS services in the UK NHS, this study quantified the administration and monitoring time burden associated with high-efficacy DMTs (alemtuzumab, cladribine tablets, fingolimod, natalizumab, and ocrelizumab) for relapsing MS. MethodsA Time and Motion (T&M) study was conducted across four MS centres in the UK, over 3–4 months per centre (Aug 2019–Feb 2021). Time dedicated by HCPs (including but not limited to neurologists, MS specialist nurses, infusion nurses, and healthcare assistants) to pre-specified drug administration and monitoring activities, elicited during pre-study interviews at each centre, was assessed for each of the selected DMTs. Administration activities included: installing peripheral access; pre-medication administration (if needed); preparing drug for infusion; infusion initiation, monitoring, and disconnection; and patient monitoring post-infusion. Monitoring activities included: booking appointments for blood draws; blood draw; retrieval and review of blood results; maintaining blood records and follow-up with the patient; checking availability of MRI results and follow-up with the patient; booking appointments for neurologist or nurse consultations; and checking patient files prior to clinic visits. A T&M model was built using observational T&M study results, data obtained through pre-study interviews, as well as stipulated monitoring intervals from relevant Summaries of Product Characteristics for the selected DMTs, to estimate active HCP time with each DMT, extrapolated over a period of 4 years per-patient. ResultsFor oral DMTs, projected total active HCP time (monitoring only) per-patient over 4 years was 14.7 h for cladribine tablets and 19.2 h for fingolimod. For infused DMTs, total time (administration and monitoring) for alemtuzumab was 37.7 h (6.0 and 31.6 h, respectively), 48.1 h for natalizumab (17.4 and 30.8 h, respectively), and 23.5 h for ocrelizumab (6.1 and 17.4 h, respectively). ConclusionsWhile active HCP time varied across centres, infused DMTs were projected to require the greatest amount of HCP time associated with administration and monitoring over 4 years versus oral DMTs. These findings may assist MS-specific HCPs in planning and delivering the equitable provision of DMT services for patients with relapsing MS.

Assessing treatment response to oral drugs for multiple sclerosis in real-world setting: a MAGNIMS Study

BackgroundThe assessment of treatment response is a crucial step for patients with relapsing-remitting multiple sclerosis on disease-modifying therapies (DMTs). We explored whether a scoring system developed within the MAGNIMS (MRI...

Factors Associated With Disease-Modifying Therapy Adherence and Persistence in Multiple Sclerosis: A Scoping Literature Review.

Patients with multiple sclerosis (MS) receiving disease-modifying therapies (DMT) show published adherence rates of 27.0% to 93.8% and published persistence rates of 49.7% to 96.5%. Improvements in DMT adherence and persistence are key to optimizing MS care, and enhanced understanding could improve MS disease management and identify research gaps. This scoping literature review aims to examine the nature and findings of the literature evaluating factors associated with DMT adherence and persistence in patients with MS. Eligible articles included in the literature review were quantitative clinical studies written in English, included adherence or persistence as primary outcomes, and accounted for covariates/confounders. The articles were assessed to identify factors associated with adherence/persistence and analyzed according to DMT type (self-injectable, oral, infusion). Fifty-eight studies (103,450 patients) were included. Study distribution by DMT type was self-injectable only (n = 41), oral only (n = 2), infusion only (n = 1), and more than 1 type (n = 14). Older age and previous DMT use were associated with increased adherence and/or persistence. Increased alcohol consumption, DMT adverse events, higher education, and higher body mass index were negatively associated with adherence and/or persistence. Greater number and severity of relapses was associated with increased adherence but decreased persistence. Most studies examined factors associated with adherence and persistence to self-injectable DMTs. These factors should be evaluated further for oral and infusion DMTs. Insights into the modifiable factors associated with adherence and persistence could guide treatment decisions and help improve adherence and clinical outcomes.

Comparative effectiveness of cladribine tablets versus fingolimod in the treatment of highly active multiple sclerosis: A real-world study.

Cladribine tablets and fingolimod have similar marketing authorisations in Europe for the treatment of patients with highly active relapsing multiple sclerosis (HA-RMS). In the absence of direct head-to-head studies, real-world data are important to assess the comparative effectiveness of these oral disease-modifying therapies (DMTs). The primary objective of the present study was to compare relapse rates between patients who received either cladribine tablets or fingolimod. This multicentre retrospective study conducted in the United Kingdom and Germany assessed non-inferiority in relapse rates of cladribine tablets versus fingolimod in HA-RMS patients over a 12-month period. Eligible patients who initiated treatment with cladribine tablets or fingolimod at least 12 months prior to the screening date were sampled consecutively until the target sample size was reached. Patients were censored at discontinuation of study treatment, commencement of another DMT, death, loss to follow-up, or at 12 months post-baseline, whichever happened earliest. The primary analytic timeframe for physician-confirmed relapse outcomes was the study effectiveness period (nine months of follow-up after an initial 12 weeks of treatment). Propensity score analysis was applied based on the inverse probability of treatment weighting approach. The primary analytic cohort consisted of 1,095 HA-RMS patients: 610 (55.7%) receiving cladribine tablets and 485 (44.3%) receiving fingolimod. Fewer patients discontinued cladribine tablets and/or switched to another DMT compared with fingolimod (0.2% versus 3.5%, respectively). The primary endpoint, adjusted annualised relapse rate (ARR), was 0.10 (95% confidence interval [CI]: 0.07-0.14) for cladribine tablets and 0.14 (95% CI: 0.10-0.20) for fingolimod. The adjusted ARR ratio of cladribine tablets versus fingolimod was 0.68 (95% CI: 0.42-1.11). Given the entire 95% CI was less than the non-inferiority margin of 1.2, cladribine tablets was non-inferior to fingolimod. In this real-world retrospective cohort study, cladribine tablets demonstrated comparable effectiveness to fingolimod at one year following treatment initiation. The full treatment dosage of cladribine tablets is completed over two years and so these results may be conservative.

Initiation Patterns of Disease-Modifying Therapies for Multiple Sclerosis Among US Adults and Children, 2001 Through 2020

Many disease-modifying therapies (DMTs) have been approved for multiple sclerosis (MS) in the past 2 decades. Research evaluating how these approvals have changed real-world prescribing patterns is scarce. To evaluate patterns in DMT initiations between 2001 and 2020 among commercially insured US adults and children with MS. This serial cross-sectional study was conducted from 2001 through 2020 (mean patient enrollment duration, 4.8 years) and used US commercial claims data (MarketScan). Analysis took place between January 2022 and March 2023. Of 287 084 patients with MS identified, 113 583 patients (113 095 adults and 488 children) with MS newly initiated at least 1 DMT. New initiation episode of a DMT, defined as no claim for the same DMT in the previous year. The proportion of total DMT initiations per year attributable to each DMT. Trends in initiations were evaluated annually. The study team identified 153 846 DMT initiation episodes among adults (median age, 46 [IQR, 38-53) years]; 86 133 female [76.2%]) and 583 among children (median age, 16 (IQR, 14-17) years; 346 female [70.9%]). Among adults, use of platform injectables showed an absolute decline of 73.8% over the study period, driven by a 61.2% reduction in interferon β initiations (P < .001 for trend). In contrast, the 2010 introduction of oral DMTs led to a rise in their use from 1.1% (2010) to 62.3% (2020) of all DMT initiations (P = .002 for trend). Infusion therapy initiations remained relatively low, accounting for 3.2% of all initiations since their introduction in 2004 but increased modestly annually after ocrelizumab was introduced (2017), reaching 8.2% of all initiations in 2020 (P < .001 for trend). Children showed similar initiation patterns, except for preferred oral therapy. Between 2019 and 2020, dimethyl fumarate was the most commonly initiated DMT in adults (23.3% to 27.2% of all initiations), while in children fingolimod was the most commonly initiated (34.8% to 68.8%). Current MS treatment guidelines emphasize shared decision-making between patients and clinicians to balance treatment efficacy, safety, cost, and convenience. This study found that oral DMTs were the predominant DMT type initiated by 2020. The cause of this shift cannot be determined from this study, but may reflect several factors, including convenience of administration, direct-to-consumer advertising, or insurance restrictions.

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.

Cost Per Relapse Avoided for Ozanimod Versus Other Selected Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis in the United States.

This study assessed the cost-effectiveness of ozanimod compared with commonly used disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS). Annualized relapse rate (ARR) and safety data were obtained from a network meta-analysis (NMA) of clinical trials of RRMS treatments including ozanimod, fingolimod, dimethyl fumarate, teriflunomide, interferon beta-1a, interferon beta-1b, and glatiramer acetate. ARR-related number needed to treat (NNT) relative to placebo and annual total MS-related healthcare costs was used to estimate the incremental annual cost per relapse avoided with ozanimod vs each DMT. ARR and adverse event (AE) data were combined with drug costs and healthcare costs to manage relapses and AEs in order to estimate annual cost savings with ozanimod vs other DMTs, assuming a 1million USD fixed treatment budget. Treatment with ozanimod was associated with lower incremental annual healthcare costs to avoid a relapse, ranging from $843,684 vs interferon beta-1a (30μg; 95% confidence interval [CI] - $1,431,619, - $255,749) to $72,847 (95%CI - $153,444, $7750) vs fingolimod. Compared with all other DMTs, ozanimod was associated with overall healthcare cost savings ranging from $8257 vs interferon beta-1a (30μg) to $2178 vs fingolimod. Compared with oral DMTs, ozanimod was associated with annual cost savings of $6199 withteriflunomide 7mg, $4737 withteriflunomide 14mg, $2178 withfingolimod, and $2793 withdimethyl fumarate. Treatment with ozanimod was associated with substantial reductions in annual drug costs and total MS-related healthcare costs to avoid relapses compared with other DMTs. In the fixed-budget analysis, ozanimod demonstrated a favorable cost-effective profile relative to other DMTs.

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.

Sphingosine-1 Phosphate Receptor Modulators Increase In Vitro Melanoma Cell Line Proliferation at Therapeutic Doses Used in Patients with Multiple Sclerosis.

S1P1 receptor modulators (S1P1-RM) are oral disease-modifying therapies (DMTs) for multiple sclerosis (MS). Several authorities have raised doubts that S1P1-RM are responsible for an increased risk of melanoma in patients with MS. We studied the in vitro effects of S1P1-RM on different melanoma cell lines to compare the effect of available S1P1-RM on the proliferation of human melanoma cells. Four S1P1-RM were studied which are currently approved for managing MS, namely fingolimod (Gilenya®), siponimod (Mayzent®), ozanimod (Zeposia®), and ponesimod (Ponvory®). We tested these four drugs at different concentrations, including therapeutic doses (0.5, 1.6, 5.5, 18, and 60µM), on human melanoma cell lines (501Mel cells, 1205LU cells, and M249R cells) to analyze in vitro cell proliferation monitored with the IncuCyte ZOOM live cell microscope (Essen Bioscience). At therapeutic doses, median confluence increased overall for all lineages: + 122% for ozanimod (p < 0.001), + 71% for ponesimod (p < 0.001), + 67% for siponimod (NS), and + 41% for fingolimod (p = 0.094). Ozanimod- and ponesimod-treated cells increased confluency in 501Mel, 1205LU, and M249R cell lines (p < 0.001). These data suggest an increased proliferation of various melanoma cell lines with S1P1-RM treatments used at therapeutic concentrations for patients with MS and should raise the question of increased dermatologic surveillance.

Low-dose naltrexone reduced anxiety in persons with multiple sclerosis during the COVID-19 pandemic.

Persons with multiple sclerosis (PwMS) have been considered at high risk for vaccination and/or acquisition of COVID-19 related to their reduced immune systems and daily regimen of immune suppressing therapy. Substantiated and unsubstantiated reports on these unknown circumstances increased anxiety and depression. Low-dose naltrexone (LDN) is a potentially effective off-label therapy shown to be effective at controlling fatigue for several autoimmune disorders including MS. This study utilized a small population of PwMS from central Pennsylvania in order to determine whether LDN therapy altered their perceived anxiety or depression during the early months of COVID-19. Utilizing mailed surveys, self-reported anxiety and depression scores were found to be significantly lower for PwMS who were prescribed LDN either alone or as an adjuvant to a standard disease modifying therapy (DMT) in comparison to those on oral disease-modifying therapies (DMTs). The data suggest that the non-toxic, inexpensive biotherapeutic may be beneficial in lessening anxiety.

Oral disease modifying therapies – A game changer for treatment decision in untreated patients with RRMS and CIS? – A swiss single center cross-sectional study

IntroductionSeveral disease-modifying therapies (DMTs) show efficacy in relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS). However, there is still a relevant proportion of patients who remain untreated. We provide real-world data on untreated and treated patients and we report whether and how the introduction of oral DMTs changed the treatment decision. Furthermore, we discuss possible reasons for not receiving DMTs. MethodsWe conducted a retrospective cross-sectional study and analysed demographic and clinical data of patients with RRMS and CIS at our MS center. Comparison was made between untreated and treated patients in 2010 (before the introduction of oral DMTs) and in 2014 (after the introduction of oral DMTs). Furthermore, we analysed reasons for the decision against DMTs in patients who never received DMTs and patients who discontinued DMTs. ResultsWe analysed datasets of 344 MS patients in 2010 and 253 in 2014. There were more untreated patients in CIS than in RRMS. In RRMS, the proportion of untreated patients decreased significantly between 2010 and 2014 from 23.6% to 11.1%, while the use of oral medications increased significantly from <1% to more than 50% in 2014. In CIS, there was no significant change in untreated patients between 2010 and 2014 (61.1% in 2010 to 52.6% in 2014). Untreated patients with RRMS were significantly older and had lower ARR than treated patients. Patients who never received DMT had lower EDSS compared to patients that had been treated before. The main reasons for the decision against DMT were "belief in a benign course" and "fear of adverse effects". Treatment discontinuation was caused mainly by the adverse effects. DiscussionIn our data a relevant proportion of patients with RRMS and CIS did not receive any DMT. We hypothesize that in patients with RRMS the introduction of oral DMTs translated to a higher rate of treatment, whereas in CIS there no change was observed. This could be due to limited therapeutic options in CIS. There is more information needed regarding the treatment recommendation for older patients and patients with mild course of the disease.

Persistence, Adherence, and Switching to Higher-Cost Therapy in Patients with Multiple Sclerosis Initiating Oral Disease-Modifying Therapies: A Retrospective Real-World Study.

Therapeutic efficacy of disease-modifying therapies (DMTs) for multiple sclerosis (MS) is often hindered by poor persistence and adherence, impacted by patient-perceived efficacy concerns, adverse effects, inconvenience, and forgetfulness. This study measured persistence, adherence, and time to switching to higher-cost therapy among patients with MS initiating teriflunomide, dimethyl fumarate, fingolimod, or diroximel fumarate treatment. This retrospective study used Symphony Health US claims data from patients with MS newly initiated on one of four oral DMTs between January and June 2020. Persistence was defined as the duration a patient continued their medication. Adherence was measured using medication possession ratio (MPR); patients with MPR ≥ 80% were considered adherent. Switching was measured by comparing proportions of patients switching and mean time to switch to one of three higher-cost therapies (ocrelizumab, natalizumab, or cladribine). Kaplan-Meier curves assessed persistence. Chi-square tests determined proportions of patients on therapy after 12months. A total of 6934 patients newly initiated on oral DMTs met study inclusion criteria (teriflunomide, n = 1968; dimethyl fumarate, n = 3409; diroximel fumarate, n = 616; fingolimod, n = 941). Patients newly initiated on teriflunomide and fingolimod had significantly higher persistence rates after 12months (60% and 66%, respectively vs 44% dimethyl fumarate and 49% diroximel fumarate; p < 0.0001), and the highest proportion of adherent patients at 6months (71% and 76%, vs 60% dimethyl fumarate and 58% diroximel fumarate) and 12months (55% and 59%, vs 40% dimethyl fumarate and 44% diroximel fumarate).Mean time to switching to higher-cost therapies ranged from 247days (diroximel fumarate to natalizumab) to 342days (teriflunomide to ocrelizumab), with the highest rate of switching in patients on dimethyl fumarate (7%). Patients newly initiated on teriflunomide and fingolimod had better real-world persistence and adherence at 6 and 12months, and longer time to switch to higher-cost therapies, than patients on dimethyl fumarate or diroximel fumarate.

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.

Systematic literature review and meta-analysis of the prevalence of secondary progressive multiple sclerosis in the USA, Europe, Canada, Australia, and Brazil

BackgroundSecondary progressive multiple sclerosis (SPMS) is a subtype of multiple sclerosis (MS), which is a chronic neurological disease, characterised by inflammation of the central nervous system. Most of MS patients eventually progress to SPMS. This study estimates the prevalence of SPMS in the United States of America, Europe, Canada, Australia, and Brazil.MethodsA systematic literature search of the Medline and Embase databases was performed using the OVID™ SP platform to identify MS epidemiological studies published in English from database inception to September 22, 2020. Studies reporting the prevalence of MS and proportion of SPMS patients in the included population were selected. The pooled prevalence of SPMS was calculated based on the proportion of SPMS patients. The Loney quality assessment checklist was used for quality grading. A meta-analysis of the proportions was conducted in RStudio.ResultsA total of 4754 articles were retrieved, and prevalence was calculated from 97 relevant studies. Overall, 86 medium- and high-quality studies were included in the meta-analysis. Most studies were conducted in European countries (84 studies). The estimated pooled prevalence of SPMS was 22.42 (99% confidence interval: 18.30, 26.95)/100,000. The prevalence of SPMS was more in the North European countries, highest in Sweden and lowest in Brazil. A decline in SPMS prevalence was observed since the availability of oral disease-modifying therapies. We also observed a regional variation of higher SPMS prevalence in urban areas compared with rural areas.ConclusionHigh variability was observed in the estimated SPMS prevalence, and the quality of the studies conducted. The influence of latitude and other factors known to affect overall MS prevalence did not fully explain the wide range of inter-country and intra-country variability identified in the results.

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...

RWD128 Profile of Patients with Multiple Sclerosis on Oral Disease-Modifying Therapies While Enrolled in North American Registry for Care and Research in Multiple Sclerosis

We characterized patients with multiple sclerosis (MS) who were receiving oral disease-modifying therapies (DMTs) at enrollment compared with all MS patients in the North American Registry for Care and Research in Multiple Sclerosis (NARCRMS).

Hiding in plain sight: The magnitude of unused disease modifying therapies in multiple sclerosis and strategies for reducing the economic burden of care

BackgroundThe rising costs associated with multiple sclerosis (MS) disease modifying therapies (DMTs) creates challenges for patients and the healthcare system in the United States (U.S.). Within a specialty medicine waste project, we quantified the magnitude of unused medications and corresponding value, the primary factors driving treatment switches, and explored reasons for discontinuations by race and ethnicity. MethodsOver one calendar year, MS DMTs were recovered from new and existing patients from a single neuroimmunologist within a tertiary MS care center. Baseline demographic and clinical information, including reasons for medication discontinuation or transitions were captured. Patients were stratified into three treatment transition categories: (i) non-medical, (ii) medical, or (iii) tolerability reasons. Cause-specific Cox proportional hazard functions were fit for possible causes for treatment changes. ResultsA total of 422 patients (female: 73.2%, median age at diagnosis: 32.9 years (y)) comprised of 86.3% Whites, 11.6% Black or African Americans, 1.4% Asians, and 0.7% Native Americans were included, representing 23% of patients evaluated within 2018, with a mean disease duration of 12.8 years (y) (standard deviation (SD): 8.2) and treatment duration of 2.9y (3.4). Women were more likely to switch due to injection fatigue or desire for an oral DMT when compared to men (95% CI [0.26, 0.78], p = 0.01). Being Black or African American people with MS increased the hazard of switching treatment due to injection fatigue and desire for an oral medication relative to White patients with MS by 91% (95% CI [1.07, 3.42], p = 0.03) and switching to a new DMT based on the subjective report of a perceived lack of efficacy was 221% greater (95% CI [1.04, 4.70], p = 0.04), but not in relation to side effects, being 50% less likely to switch (95% CI [0.28, 0.90], p = 0.02). In the passive recruitment phase over a single calendar year, DMTs with a retail value of $5.2 million (Average Wholesale Price (AWP)) were recovered. In the 1-month active recruitment phase within the same year involving 49 people with MS, unused MS DMTs of $1.1 million (AWP) were acquired. Of the 471 patients studied, 56.2% reported transitions in DMTs for reasons other than adequate disease control and tolerability at one point in their treatment history, underscoring the need for individualized therapy selections that enhance persistence and increase the likelihood of reducing further neurological disability. ConclusionThe magnitude of unused and wasted MS DMTs is staggering and these findings allude to a larger, more pervasive problem within the healthcare system with financial resources being applied to therapies that go unused.

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.