Prior Disease-modifying Therapy Research Articles

Costs of Potential Medication Wastage Due to Switching Treatment Among People With Multiple Sclerosis.

Background: Unused medications negatively impact healthcare resource utilization and environmental safety, contribute substantially to annual healthcare expenditures, and may ultimately affect patient health outcomes. People with multiple sclerosis (PwMS) commonly switch disease-modifying therapies (DMTs), leading to medication wastage and substantial costs for insurers and patients. Objectives: To estimate the cost associated with potential medication wastage (PMW) in a subcohort of PwMS receiving oral or self-injectable US Food and Drug Administration-approved DMTs who switched DMTs in a calendar year in the United States. Methods: This retrospective cohort study included adults with MS and used PharMetrics® Plus claims data from 2017 to 2021. PwMS were required to have 12 months of continuous eligibility for the entire year and a claim for at least 2 unique DMTs during the same calendar year. The PMW cohort was defined as those who had an aggregate overlap in days' supply across DMT switches within the year; those in the non-PMW cohort did not. The cost of PMW for insurers and PwMS due to overlap was calculated only at the point of switch to the new DMT and defined as the cost of the remaining days' supply of the prior DMT. Results: The number of PwMS meeting the inclusion criteria was 1762 in 2017, 1947 in 2018, 1679 in 2019, 1461 in 2020, and 1782 in 2021. Approximately 95% of PwMS switched DMTs once within single calendar years, and 25% (n = 381-464) contributed to PMW. For those who had overlapping DMT supply, it was estimated that 34% to 38% of the DMT being switched from was potentially wasted. The total cost of PMW paid by the insurer and PwMS ranged from 1 489 859. While most of the total cost ( 1 450 328) was paid by the insurer, PwMS still owed substantial amounts ( 74 578). Across all PwMS, the per person per year cost ranged from 846. The estimated wastage and associated costs were consistent across all study years. Conclusions: DMT switching is common among PwMS, resulting in PMW and high costs to patients and insurers.

Costs of Potential Medication Wastage Due to Switching Treatment Among People With Multiple Sclerosis

Background: Unused medications negatively impact healthcare resource utilization and environmental safety, contribute substantially to annual healthcare expenditures, and may ultimately affect patient health outcomes. People with multiple sclerosis (PwMS) commonly switch disease-modifying therapies (DMTs), leading to medication wastage and substantial costs for insurers and patients. Objectives: To estimate the cost associated with potential medication wastage (PMW) in a subcohort of PwMS receiving oral or self-injectable US Food and Drug Administration–approved DMTs who switched DMTs in a calendar year in the United States. Methods: This retrospective cohort study included adults with MS and used PharMetrics® Plus claims data from 2017 to 2021. PwMS were required to have 12 months of continuous eligibility for the entire year and a claim for at least 2 unique DMTs during the same calendar year. The PMW cohort was defined as those who had an aggregate overlap in days’ supply across DMT switches within the year; those in the non-PMW cohort did not. The cost of PMW for insurers and PwMS due to overlap was calculated only at the point of switch to the new DMT and defined as the cost of the remaining days’ supply of the prior DMT. Results: The number of PwMS meeting the inclusion criteria was 1762 in 2017, 1947 in 2018, 1679 in 2019, 1461 in 2020, and 1782 in 2021. Approximately 95% of PwMS switched DMTs once within single calendar years, and 25% (n = 381-464) contributed to PMW. For those who had overlapping DMT supply, it was estimated that 34% to 38% of the DMT being switched from was potentially wasted. The total cost of PMW paid by the insurer and PwMS ranged from $1 200 866 to $1 489 859. While most of the total cost ($1 172 140-$1 450 328) was paid by the insurer, PwMS still owed substantial amounts ($28 726-$74 578). Across all PwMS, the per person per year cost ranged from $716 to $846. The estimated wastage and associated costs were consistent across all study years. Conclusions: DMT switching is common among PwMS, resulting in PMW and high costs to patients and insurers.

Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60

BackgroundOngoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher...

Effect of Prior Treatment With Fingolimod on Early and Late Response to Rituximab/Ocrelizumab in Patients With Multiple Sclerosis.

Real-life studies noted that the risk of disease activity in multiple sclerosis (MS) after switching to rituximab (RTX) or ocrelizumab (OCR) may be unequal depending on prior disease-modifying therapy (DMT), with a higher risk associated with fingolimod (FING). We performed a retrospective analysis of a structured prospective data collection including all consecutive patients with relapsing MS who were prescribed RTX/OCR in the MS center of Marseille. Cox proportional hazards models were applied to clinical and MRI outcomes. We included 321 patients with a median (interquartile range [IQR]) follow-up of 3.5 years (1.5-5) after RTX/OCR initiation. At the first RTX/OCR infusion, the mean (SD) age of patients was 37 (10) years, and the median (IQR) disease duration was 8 years (3-15): 68 patients did not receive treatment before RTX/OCR and 108 switched from FING, 47 from low efficacy therapy, and 98 from natalizumab. For statistical analysis, the group "FING" was divided into "short-FING" and "long-FING" groups according to the median value of the group's washout period (27 days). On Cox proportional hazards analysis, for only the "long-FING" group, the risk of relapse within the first 6 months of RTX/OCR was increased as compared with patients without previous DMT (hazard ratio [HR]: 8.78; 95% CI 1.72-44.86; p < 0.01). Previous DMT and washout period duration of FING had no effect on B-cell levels at 6 months. Beyond the first 6 months of RTX/OCR, age <40 years was associated with increased risk of relapse (HR: 3.93; 95% CI 1.30-11.89; p = 0.01), male sex with increased risk of new T2 lesions (HR: 2.26; 95% CI 1.08-4.74; p = 0.03), and EDSS ≥2 with increased risk of disability accumulation (HR: 3.01; 95% CI 1.34-6.74; p < 0.01). Previous DMT had no effect on the effectiveness of RTX/OCR beyond 6 months after initiation. For patients switching from FING to RTX/OCR, the risk of disease reactivation within the first 6 months of treatment was increased as compared with patients with other DMT or no previous DMT only when the washout period exceeded 26 days. Neither FING nor other previous DMT reduced the effectiveness of RTX/OCR beyond the first 6 months of treatment.

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.

Clinical characterization of long-term multiple sclerosis (COLuMbus) patients in Argentina: A cross-sectional non-interventional study

BackgroundMost Multiple Sclerosis (MS) clinical trials fail to assess the long-term effects of disease-modifying therapies (DMT) or disability. MethodsCOLuMbus was a single-visit, cross-sectional study in Argentina in adult patients with ≥10 years of MS since first diagnosis. The primary endpoint was to determine patient disability using the Expanded Disability Status Scale (EDSS). The secondary endpoints were to evaluate the distribution of diagnoses between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), patient demographics, disease history, and the risk of disability progression. The relationship between baseline characteristics and the current disability state and the risk of disability progression was assessed. ResultsOut of the 210 patients included, 76.7 % had a diagnosis of RRMS and 23.3 % had been diagnosed with SPMS, with a mean disease duration of 17.9 years and 20.5 years, respectively. The mean delay in the initial MS diagnosis was 2.6 years for the RRMS subgroup and 2.8 years for the SPMS subgroups. At the time of cut-off (28May2020), 90.1 % (RRMS) and 75.5 % (SPMS) of patients were receiving a DMT, with a mean of 1.5 and 2.0 prior DMTs, respectively. The median EDSS scores were 2.5 (RRMS) and 6.5 (SPMS). In the RRMS and SPMS subgroups, 23 % and 95.9 % of patients were at high risk of disability, respectively; the time since first diagnosis showed a significant correlation with the degree of disability. ConclusionsThis is the first local real-world study in patients with long-term MS that highlights the importance of recognizing early disease progression to treat the disease on time and delay disability.

Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6months for 2years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and theTreatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18months (p = 0.004) and 29.0 (24.6) at 24months (p = 0.002). Levels of fatigue and depression were also reduced. After 2years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2years is effective in reducing ARR and disability progression.

Real-world use of ofatumumab to treat multiple sclerosis 9 months post-FDA approval during COVID-19 pandemic.

Relapsing multiple sclerosis (MS) is an inflammatory, demyelinating, neurodegenerative disease of the central nervous system that causes episodes of neurological dysfunction (relapse) alternating with variable intervals of stability. Disease-modifying therapies (DMTs) aim to reduce the rate of relapse and slow disease progression in people with MS, particularly in those with relapsing MS. Ofatumumab is a fully human anti-CD20 monoclonal antibody approved to treat patients with relapsing forms of MS. This study describes the demographics, clinical characteristics, and prior DMT use of patients with at least one ofatumumab prescription claim following approval by the United States (US) Food and Drug Administration (FDA). Understanding ofatumumab utilization patterns and patient characteristics can help define the journey of patients with MS and aid future clinical decision-making. This retrospective study is based on data from IQVIA's Longitudinal Prescription Data (LRx) and Medical Claims (Dx) databases in the US, collected between August 01, 2019 and May 31, 2021. The index date was defined as the date of the first ofatumumab prescription. The pre-index period was defined as the 12 months prior to the index date. Adult patients (aged ≥18 years) with a diagnosis of MS and at least one prescription for ofatumumab between August 2020 and May 2021 in the LRx database were included. Only patients with at least one medical claim in the Dx database and a diagnosis of MS 24 months prior to the index date were included. Descriptive analyses were conducted 3, 6, and 9 months after FDA approval. Overall, 3,600 patients with a prescription for ofatumumab were identified in the LRx claims database, and 2,101 patients remained in the study after inclusion and exclusion criteria had been applied. At the 9-month post-approval time point, patients with ofatumumab claims were characterized as primarily female (74%) and middle-aged (median age: 48 years); two-thirds (64.7%) had a mild MS disability level. Patients were otherwise generally healthy with limited comorbid conditions. Most patients (81.7%) in the study did not experience relapse during the pre-index period. DMT-naïve patients who were prescribed ofatumumab at 3, 6, and 9 months post-approval accounted for 46.9%, 54.8%, and 58.4% of the study population, respectively. Over time, this increase in DMT-naïve ofatumumab initiators was statistically significant (p=0.0003). Among patients who had been treated with DMTs during the previous year, most had taken them orally (50.6%), some had received them via intravenous infusion (32.2%), and some via subcutaneous/intramuscular injection (21.1%). Intravenous ocrelizumab was the most common DMT switch observed (n=205, 23.4%) among these patients. This real-world study is the first to describe patients treated with ofatumumab since FDA approval during the COVID-19 pandemic. The majority of patients in this study were middle-aged women with mild MS symptoms. Ofatumumab was increasingly used as a first-line DMT. Additionally, a number of patients aged ≥55 years (beyond the trial population) used ofatumumab, which may suggest expanding clinician confidence in the safety and clinical utility of ofatumumab therapy. However, future long-term observational studies are needed to confirm these results.

Long-term results of autografting persons with multiple sclerosis are better in those not exposed to prior disease-modifying therapies.

Multiple sclerosis (MS) is a disabling disease that affects young adults. Treatments for MS have increased exponentially in number, efficacy and risk. Autologous hematopoietic stem cell transplantation (aHSCT) can change the natural history of the disease. To analyze if aHSCT should be done early in the course of the disease or after failing of other therapies, we have studied the long-term results of aHSCT in a cohort of persons with MS who were given, or not, immunosuppressive drugs before the transplant. Patients with MS referred to our center for aHSCT between June 2015 and January 2023 were prospectively entered in the study. All phenotypes of MS were included (relapsing remitting, primary progressive and secondary progressive). The follow up was assessed with the patient reported EDSS score in an online form; only patients followed by three or more years were included in the analysis. Patients were divided into two groups: Given or not disease modifying treatments (DMT) before the aHSCT. 1132 subjects were prospectively enrolled. 74 patients were followed for more than 36 months, and the subsequent analysis was done in this cohort. The response rate (RR=improvement+stabilization) at 12, 24 and 36 mo was 84%, 84% and 58% respectively for patients not receiving prior DMT and 72%, 90% and 67% for patients receiving DMT. In the whole group, the EDSS score dropped from a mean of 5.5 to 4.5 at 12 mo, to 5.0 at 24 mo and to 5.5 at 36 mo, after the aHSCT. The EDSS score was on average worsening in patients before the aHSCT, but the transplant stabilized the EDSS score at 3 years in patients with prior exposure to DMT, whereas in persons not given DMT, the transplant resulted in a significant decrease (p=.01) of the EDSS score. This indicates a positive response in all patients given aHSCT, but significantly better in those not exposed to DMT before the graft. The response to aHSCT was better for persons not exposed to immunosuppressive DMT before the transplant, thus suggesting that aHSCT should be done early in the course of the disease and probably before the treatment with DMT. Additional studies are needed to further analyze the impact of the use of DMT therapies before the aHSCT in MS, as well as the timing of the procedure.

Ublituximab Efficacy in Treatment-Naive Participants With Relapsing Multiple Sclerosis in the Phase 3 ULTIMATE I and II Studies (P6-3.015)

Ublituximab Efficacy in Treatment-Naive Participants With Relapsing Multiple Sclerosis in the Phase 3 ULTIMATE I and II Studies (P6-3.015)

Early clinical experience with cladribine tablets in a Black/Hispanic patient population (P9-3.001)

<h3>Objective:</h3> To report our early experience using cladribine tablets in a real-world US cohort of MS patients and of a subgroup who were Black/Hispanic. Outcomes presented include patient characteristics, previous DMT use, safety, and lymphocyte counts of both groups. <h3>Background:</h3> The efficacy and safety of cladribine tablets 3.5 mg/kg was demonstrated in clinical trials; however, the real-world clinical experience is still emerging. An area of growing interest is the use of disease-modifying therapies (DMTs) in racial minorities with multiple sclerosis (MS) as they have distinct disease characteristics but historically low participation in clinical trials. Understanding the risk/benefit profile of this therapy in these populations are of extreme importance. <h3>Design/Methods:</h3> Prospective and retrospective chart review of 72 patients with RMS who were treated with ≥1 course of cladribine tablets. A subgroup analysis was also performed for patients who were Black/Hispanic (n=26) <h3>Results:</h3> We report on 72 patients who have initiated therapy with cladribine tablets by data cut-off (June 2021). Median age at cladribine tablets initiation was 46 years (range 24–71) and 36% of patients were Black/Hispanic. Median disease duration was 13 years (range 2–34) and median baseline EDSS was 3.5 (range 0–7.5). The mean number of prior DMTs was 2.5 and 31% of patients completed both treatment courses by data cut-off. Overall, cladribine tablets were well tolerated. 57% of patients experienced lymphopenia with no grade 4 reported. No serious adverse events occurred. Updated data including preliminary efficacy data will be presented. <h3>Conclusions:</h3> In this cohort of patients initiating cladribine tablets in the real-world, the initial treatment was well-tolerated, even among those who are Black/Hispanic. The side effect profile was consistent with that seen in the clinical trial program. Ongoing follow-up will further expand on these results as more patients complete their full treatment course. <b>Disclosure:</b> Dr. Gutierrez has nothing to disclose. Dr. Ochoa has nothing to disclose.

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

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

Prediction of relapse activity when switching to cladribine for multiple sclerosis

Background: Patients with relapsing–remitting multiple sclerosis commonly switch between disease-modifying therapies (DMTs). Identifying predictors of relapse when switching could improve outcomes. Objective: To determine predictors of relapse hazard when switching to cladribine. Methods: Data of patients who switched to cladribine, grouped by prior disease-modifying therapy (pDMT; interferon-β/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab (NTZ)), were extracted from the MSBase Registry. Predictors of relapse hazard during the treatment gap and the first year of cladribine therapy were determined. Results: Of 513 patients, 22 relapsed during the treatment gap, and 38 within 1 year of starting cladribine. Relapse in the year before pDMT cessation predicted treatment gap relapse hazard (hazard ratio (HR) = 2.43, 95% confidence interval (CI) = 1.03–5.71). After multivariable adjustment, relapse hazard on cladribine was predicted by relapse before pDMT cessation (HR = 2.00, 95% CI = 1.01–4.02), treatment gap relapse (HR = 6.18, 95% confidence interval (CI) = 2.65–14.41), switch from NTZ (HR compared to injectable therapies 4.08, 95% CI = 1.35–12.33) and age at cladribine start (HR = 0.96, 95% CI = 0.91–0.99). Conclusion: Relapse during or prior to the treatment gap, and younger age, are of prognostic relevance in the year after switching to cladribine. Switching from NTZ is also independently associated with greater relapse hazard.

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

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

Health-Related Quality of Life with Diroximel Fumarate in Patients with Relapsing Forms of Multiple Sclerosis: Findings from Qualitative Research Using Patient Interviews.

IntroductionDiroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS). Clinical and real-world studies of DRF have demonstrated improved gastrointestinal (GI) tolerability and low (< 1%) GI-related treatment discontinuation versus dimethyl fumarate (DMF) and high rates of treatment adherence. Our aim was to conduct a concept elicitation study to identify treatment-related concepts most meaningful to patients and to evaluate how these concepts shape the patient perspective of DRF.MethodsIn-depth qualitative interviews were conducted with patients from October to December 2020. US adults who had been prescribed DRF through routine clinical care and had taken DRF for ≥ 3 weeks in the past 6 months were eligible to participate. Semi-structured interviews explored patient perceptions on treatment selection and impact.ResultsSeventeen patients participated in the study. Mean (SD) age was 49.3 (12.0) years. Sixteen patients reported prior disease-modifying therapy, while 10 (58.8%) had prior DMF. DRF treatment duration ranged from ~ 6 weeks to 10 months. Four key concepts emerged: (1) overall wellness and quality of life, (2) ease of administration, (3) minimal and manageable side effects, and (4) patient optimism due to MS treatments. Mode of administration (82.4%), no/mild side effects (70.6%), convenience over injectable/infusion medications (58.8%), and effectiveness (64.7%) were cited as positive aspects of DRF treatment. Frequent dosing (52.9%) and food requirements (41.2%) were cited as negative attributes; however, 94.1% had no dietary changes since starting treatment.ConclusionThe patient perspective is a key aspect when considering a disease-modifying therapy for MS, given the multitude of options currently available. Overall wellness, ease of administration, and minimal and manageable side effects were DRF-related concepts most meaningful to patients on therapy. Acknowledging these patient perceptions in shared decision-making may lead to greater patient adherence and optimal treatment outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02164-8.

Effectiveness of Natalizumab Treatment Inpatients With Early Relapsing-Remitting Multiple Sclerosis (RRMS) who were Treatment-Naive Versus Those Who Had Prior Disease-Modifying Therapy (DMT) Use (P6-4.006)

Effectiveness of Natalizumab Treatment Inpatients With Early Relapsing-Remitting Multiple Sclerosis (RRMS) who were Treatment-Naive Versus Those Who Had Prior Disease-Modifying Therapy (DMT) Use (P6-4.006)

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry.

ObjectiveTo describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry.MethodsAn observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve.ResultsSix hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs.ConclusionsThe patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.

Prediction of multiple sclerosis outcomes when switching to ocrelizumab

Background: Increasingly, people with relapsing-remitting multiple sclerosis (RRMS) are switched to highly effective disease-modifying therapies (DMTs) such as ocrelizumab. Objective: To determine predictors of relapse and disability progression when switching from another DMT to ocrelizumab. Methods: Patients with RRMS who switched to ocrelizumab were identified from the MSBase Registry and grouped by prior disease-modifying therapy (pDMT; interferon-β/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab) and washout duration (<1 month, 1–2 months or 2–6 months). Survival analyses including multivariable Cox proportional hazard regression models were used to identify predictors of on-ocrelizumab relapse within 1 year, and 6-month confirmed disability progression (CDP). Results: After adjustment, relapse hazard when switching from fingolimod was greater than other pDMTs, but only in the first 3 months of ocrelizumab therapy (hazard ratio (HR) = 3.98, 95% confidence interval (CI) = 1.57–11.11, p = 0.004). The adjusted hazard for CDP was significantly higher with longer washout (2–6 m compared to <1 m: HR = 9.57, 95% CI = 1.92–47.64, p = 0.006). Conclusion: The risk of disability worsening during switch to ocrelizumab is reduced by short treatment gaps. Patients who cease fingolimod are at heightened relapse risk in the first 3 months on ocrelizumab. Prospective evaluation of strategies such as washout reduction may help optimise this switch.

Long-Term Effectiveness of Natalizumab in Patients with Relapsing-Remitting Multiple Sclerosis Treated in the Routine Care in Greece: Results from the Multicenter, Observational 5-Year Prospective Study 'TOPICS Greece'.

Background and ObjectivesFor chronic diseases like multiple sclerosis (MS), real-world evidence on long-term treatment outcomes is essential. The study aimed to provide long-term data on the safety and effectiveness of natalizumab in patients with relapsing-remitting MS (RRMS) treated in a routine care setting in Greece.MethodsTOPICS Greece was a multicenter, single-country, prospective 5-year observational study.ResultsBetween 19-Apr-2012 and 18-Dec-2014, 304 eligible adults [females: 63.2%; median age at natalizumab initiation: 38.0 years; median disease duration: 6.2 years; median Expanded Disability Status Scale (EDSS) score at baseline: 3.5] were enrolled in the study by 20 hospital-based neurologists. The 1-year annualized relapse rate (ARR) before treatment initiation was 1.859, while the ARR during the first year of treatment was 0.131, representing a significant 93% reduction (p < 0.001). The ARR over the median treatment period of 59.4 months was 0.109. Patients with ≤1 relapse in the pre-natalizumab year (46.1%) and those having received ≤1 prior disease-modifying therapy (57.9%) displayed significantly lower on-natalizumab ARR. The 1-, 2-, 3-, 4- and 5-year cumulative probabilities of EDSS progression were 3.2, 6.2, 9.7, 13.4, and 17.4%, respectively; the respective probabilities of EDSS disability improvement were 18.3, 25.1, 27.4, 28.0, and 30.1%. Over a median safety data collection period of 48.7 months, 4.6% of the patients experienced ≥ 1 serious adverse event, with infections (reported in 1.0%) being the most common.ConclusionIn real-world settings in Greece, natalizumab displayed beneficial long-term effects on disease activity and disability progression consistent with previous studies with no new serious safety signals emerging.

Ocrelizumab treatment for relapsing-remitting multiple sclerosis after a suboptimal response to previous disease-modifying therapy: A nonrandomized controlled trial

Background: Many patients with multiple sclerosis (MS) experience suboptimal disease control despite the use of disease-modifying therapy (DMT). Objective: To assess the efficacy and safety of ocrelizumab (OCR) in patients with relapsing-remitting MS (RRMS) and suboptimal response to prior DMTs. Methods: Patients with RRMS and suboptimal responses (one clinically reported relapse and/or lesion activity) after ⩾ 6 months on another DMT were enrolled. OCR 600 mg was given intravenously every 24 weeks. The primary outcome was no evidence of disease activity (NEDA), defined as the absence of protocol-defined relapse, confirmed disability progression (CDP), T1 Gd-enhancing lesions, and new/enlarging T2 lesions. Results: The intention-to-treat (ITT) population included 608 patients; NEDA was analyzed in a modified ITT (mITT) population (n = 576 (94.7%)). Over 96 weeks, 48.1% of mITT patients achieved NEDA, and most were free from protocol-defined relapse (89.6%), CDP (89.6%), and T1 Gd-enhancing lesions (95.5%); 59.5% had no new/enlarging T2 lesions. Safety observations were consistent with findings in the pivotal trials. Conclusion: Consistent efficacy of OCR on clinical and magnetic resonance imaging (MRI) disease activity measures and progression was shown in patients with RRMS and a suboptimal response to prior DMTs; no new safety signals were observed.