High-efficacy Disease-modifying Therapies Research Articles

Ocrelizumab and ofatumumab comparison: an Italian real-world propensity score matched study.

The management of Multiple Sclerosis (MS) has undergone transformative evolution with the introduction of high-efficacy disease-modifying therapies (DMTs), specifically anti-CD20 monoclonal antibodies, such as ocrelizumab (OCR) and ofatumumab (OFA). This is an independent retrospective cohort study in Relapsing MS (RMS) patients followed at eight Italian MS centers who initiated treatment with OCR or OFA in the participating centers and with at least 12months on therapy. A generalized linear regression model inverse probability of treatment weight (IPTW) PS-adjusted was performed to evaluate the relationship between annualized relapse rate (ARR) and treatment groups. No evidence of disease activity-NEDA-3 at 12-month score was also collected. Safety profile of the investigated DMTs was recorded. A total cohort of 396 RMS patients fulfilled the required criteria and were enrolled in the study. Out of them, 216 had a prescription of OCR and 180 of OFA. The mean follow-up was 13.2 ± 1.9months. The estimated means for ARR did not show differences between the two groups, 0.059 for patients on OCR and 0.038 for patients on OFA (p = 0.185). The generalized regression model IPTW PS-adjusted did not reveal differences between patients on OCR and OFA (ExpBOFA 0.974, 95%CI 934-1.015, p = 0.207). NEDA-3 at 12months was experienced by 199(92.1%) patients on OCR and 170(94.4%) patients on OFA (p = 0.368). Generally, both therapies exhibit good tolerability. The treatment with OCR and OFA resulted in comparable control of disease activity with good safety profile. Our results need further validation in larger multicentre studies with long-term follow-up.

Long-term neuroprotective effects of natalizumab and fingolimod in multiple sclerosis: evidence from real-world clinical data

BackgroundThe long-term effect of high efficacy disease modifying therapy (DMT) on neurodegeneration in people with multiple sclerosis (pwMS) is largely unknown. The aim of this study was to evaluate the long-term effect of natalizumab (NTZ) or fingolimod (FTY) therapy on the evolution of brain atrophy compared to moderate efficacy DMT in a real-world clinical setting. MethodsA total of 438 pwMS with 2,439 MRI exams during treatment were analyzed: 252 pwMS treated with moderate efficacy DMT, 130 with NTZ and 56 with FTY. Evolution of brain atrophy was analyzed over an average follow-up of 6.6 years after treatment initiation. Brain segmentation was performed on clinical 3D-FLAIRs using SynthSeg and regional brain volume changes over time were compared between the treatment groups. ResultsTotal brain, white matter and deep gray matter atrophy rates did not differ between moderate efficacy DMTs, NTZ and FTY. Annualized ventricle growth rates were lower in pwMS treated with NTZ (1.1%/year) compared with moderate efficacy DMT (2.4%/year, p<0.001) and similar to FTY (2.0%/year, p=0.051). Cortical atrophy rates were lower in NTZ (-0.08%/year) compared with moderate efficacy DMT (-0.16%/year, p=0.048). ConclusionIn a real-world clinical setting, pwMS treated with NTZ had slower ventricular expansion and cortical atrophy compared to those treated with moderate efficacy DMT.

Escalating to medium- versus high-efficacy disease modifying therapy after low-efficacy treatment in relapsing remitting multiple sclerosis.

In patients with relapsing remitting multiple sclerosis (RRMS) on low-efficacy disease modifying therapies (DMT), the optimal strategy on how to escalate treatment once needed, remains unknown. We studied RRMS patients on low-efficacy DMTs listed in the Swiss National Treatment Registry, who underwent escalation to either medium- or high-efficacy DMTs. Propensity score-based matching was applied using 12 clinically relevant variables. Both groups were also separately matched with control subjects who did not escalate therapy. Time to relapse and to disability worsening were evaluated using Cox proportional hazard models. Of 1037 eligible patients, we 1:1 matched 450 MS patients who switched from low-efficacy to medium-efficacy (n=225; 76.0% females, aged 42.4±9.9 years [mean±SD], median EDSS 3.0 [IQR 2-4]) or high-efficacy DMTs (n=225; 72.4% females, aged 42.2±10.6 years, median EDSS 3.0 [IQR 2-4]). Escalation to high-efficacy DMTs was associated with lower hazards of relapses than medium-efficacy DMTs (HR=0.67, 95% CI 0.47-0.95, p=.027) or control subjects (HR=0.61, 95% CI 0.44-0.84, p=.003). By contrast, escalation from low to medium-efficacy DMTs did not alter the hazard for relapses when compared to controls (i.e. patients on low-efficacy DMT who did not escalate DMT during follow-up) CONCLUSION: Our nationwide registry analysis suggests that, once escalation from a low-efficacy DMT is indicated, switching directly to a high-efficacy treatment is superior to a stepwise escalation starting with a moderate-efficacy treatment.

Association of serum glial fibrillary acidic protein with progression independent of relapse activity in multiple sclerosis.

Insidious disability worsening is a common feature in relapsing-remitting multiple sclerosis (RRMS). Many patients experience progression independent of relapse activity (PIRA) despite being treated with high efficacy disease-modifying therapies. We prospectively investigated associations of body-fluid and imaging biomarkers with PIRA. Patients with early RRMS (n = 104) were prospectively included and followed up for 60months. All patients were newly diagnosed and previously untreated. PIRA was defined using a composite score including the expanded disability status scale, 9-hole peg test, timed 25 foot walk test, and the symbol digit modalities test. Eleven body fluid and imaging biomarkers were determined at baseline and levels of serum neurofilament light (sNfL) and glial fibrillary acidic protein (sGFAP) were also measured annually thereafter. Association of baseline biomarkers with PIRA was investigated in multivariable logistic regression models adjusting for clinical and demographic confounding factors. Longitudinal serum biomarker dynamics were investigated in mixed effects models. Only sGFAP was significantly higher in PIRA at baseline (median [IQR] 73.9 [60.9-110.1] vs. 60.3 [45.2-79.9], p = 0.01). A cut-off of sGFAP > 65 pg/mL resulted in a sensitivity of 68% and specificity of 61%, to detect patients at higher risk of PIRA. In a multivariable logistic regression, sGFAP > 65 pg/mL was associated with higher odds of developing PIRA (odds ratio 4.3, 95% CI 1.44-12.86, p = 0.009). Repeated measures of sGFAP levels showed that patients with PIRA during follow-up had higher levels of sGFAP along the whole follow-up compared to stable patients (p < 0.001). Determination of sGFAP at baseline and follow-up may be useful in capturing disability accrual independent of relapse activity in early RRMS.

Patterns of multiple sclerosis presentation to the emergency department.

Multiple sclerosis (MS) patients are no strangers to the emergency department (ED) due to the relapsing and progressive nature of the disease and the associated complications. This study aimed to identify patterns of ED visits among patients diagnosed with MS, the underlying causes of these visits, and the factors associated with these visits. This was a single center retrospective cohort study which utilized a non-probability consecutive sampling technique to include all patients diagnosed with MS (471 patients) from March 2016 to October 2021 in King Abdulaziz Medical City, Jeddah, Saudi Arabia. ED visits were categorized as directly related to MS, indirectly related to MS, or unrelated to MS. One in four people with MS visited the ED at least once with a total of 280 ED visits. Most ED visits were ones directly related to MS 43.6%, closely followed by unrelated to MS 41.1%, and then indirectly-related MS visits 15.4%. The most common presenting symptoms in directly-related MS visits were weakness 56.6% and numbness/tingling 56.6% followed by gait impairment 29.5%. Indirectly related to MS or unrelated to MS ED visits were commonly due to neurological 17.7% and gastrointestinal 17.1% causes. Using disease modifying therapy (DMT) was significantly associated with no ED visits (p < 0.001). The use of high-efficacy DMTs was significantly associated with no ED visits than using moderate efficacy DMT (p < 0.001). The use of B-cell depleting therapy (ocrelizumab and rituximab) was significantly associated with no visits to the ED than using any other DMT (p < 0.001). Evidence of brain atrophy on imaging was significantly associated with patients who presented to the ED ≥3 times (p = 0.006, UOR = 3.92). Due to the nature of the disease, many MS patients find themselves visiting the ED due to MS related and unrelated issues. These patients are not only required to be treated by neurologists but also by multiple disciplines. The use of high-efficacy DMTs and B-cell depleting therapy may reduce the total frequency of ED visits. Special attention should be paid to patients who have evidence of brain atrophy on imaging.

NEDA-3 achievement in early highly active relapsing remitting multiple sclerosis patients treated with Ocrelizumab or Natalizumab

Backgroundin the early stages of Multiple Sclerosis (MS), initiating high-efficacy disease-modifying therapy (HE DMTs) may represent an optimal strategy for delaying neurological damage and long-term disease progression, especially in highly active MS patients (HAMS). Natalizumab (NAT) and Ocrelizumab (OCR) are recognized as HE DMTs with significant anti-inflammatory effects. This study investigates NEDA-3 achievement in treatment-naïve HAMS patients receiving NAT or OCR over three years. Methodswe retrospectively enrolled treatment-naïve HAMS patients undergoing NAT or OCR, collecting demographic, clinical, and instrumental data before and after treatment initiation to compare with propensity score analysis disease activity, time to disability worsening, and NEDA-3 achievement. Resultswe recruited 281 HAMS patients with a mean age of 32.7 years (SD 10.33), treated with NAT (157) or OCR (124). After three years, the Kaplan-Meier probability of achieving NEDA-3 was 66.0 % (95 % CI: 57.3 % - 76.0 %) with OCR and 68.2 % (95 % CI: 59.9 % - 77.7 %) with NAT without significant differences between the two groups (p = 0.27) Discussion and conclusionstarting HE DMT with monoclonal antibodies for HAMS could achieve NEDA-3 in a high percentage of patients without differences between NAT or OCR.

Clinical Characteristics and Long-Term Outcomes of Late-Onset Multiple Sclerosis: A Swedish Nationwide Study.

Clinical onset of multiple sclerosis (MS) after the age of 50 years is uncommon and associated with a less favorable natural history. The differences in long-term outcomes in patients with late-onset MS (LOMS, onset 50 years or older) and adult-onset MS (AOMS, onset 18 years or older and younger than 50 years) during the disease-modifying therapy (DMT) era have been less studied. This study aimed to compare patient characteristics, DMT exposure, and disability progression in Swedish patients with LOMS and AOMS over 2 decades (2001-2022). The nationwide Swedish MS registry was searched for patients with an onset of MS between January 1, 2001, and December 31, 2018, with symptom onset at age 18 years or older and ≥2 recorded Expanded Disability Status Scale (EDSS) scores. Clinical and demographic parameters and exposure to DMT were compared between LOMS and AOMS. Time to disability milestones (EDSS 4 and 6) was assessed using Kaplan-Meier curves and Cox proportional hazards regression models adjusted for sex, disease course, calendar year at onset, and DMT exposure. Among 8739 patients with MS who met inclusion criteria, 1,028 (11.8%) were LOMS. Primary progressive MS was more frequently diagnosed in LOMS compared with that in AOMS (25.2% vs 4.5%; p < 0.001). Most of the patients had been prescribed DMT, but more rarely in LOMS compared with AOMS (74.7% vs 95.6%; p < 0.001). Less than half of patients with LOMS had been exposed to a high-efficacy DMT (45.8%) compared with 73.5% of AOMS (p < 0.001). The risk of reaching disability milestones was greater for LOMS compared with that for AOMS (EDSS 4; adjusted hazard ratio [aHR] 2.71; 95% CI 2.22-3.30; p < 0.001, and EDSS 6; aHR 2.67; 95% CI 2.12-3.36; p < 0.001). This study distinguishes LOMS as a particularly vulnerable group and clinically supports close vigilance of these patients. Further studies are needed to assess and clarify the benefit of DMT usage in older adults with MS.

Holistic, Long-Term Management of People with Relapsing Multiple Sclerosis with Cladribine Tablets: Expert Opinion from France.

Cladribine tablets (CladT) has been available for therapeutic use in France since March 2021 for the management of highly active relapsing multiple sclerosis (RMS). This high-efficacy disease-modifying therapy (DMT) acts as an immune reconstitution therapy. In contrast to most high-efficacy DMTs, which act via continuous immunosuppression, two short courses of oral treatment with CladT at the beginning of years 1 and 2 of treatment provide long-term control of MS disease activity in responders to treatment, without the need for any further pharmacological treatment for several years. Although the labelling for CladT does not provide guidance beyond the initial treatment courses, real-world data on the therapeutic use of CladT from registries of previous clinical trial participants and patients treated in routine practice indicate that MS disease activity is controlled for a period of years beyond this time for a substantial proportion of patients. Moreover, this clinical experience has provided useful information on how to initiate and manage treatment with CladT. In this article we, a group of expert neurologists from France, provide recommendations on the initiation of CladT in DMT-naïve patients, how to switch from existing DMTs to CladT for patients with continuing MS disease activity, how to manage patients during the first 2years of treatment and finally, how to manage patients with or without MS disease activity in years 3, 4 and beyond after initiating treatment with CladT. We believe that optimisation of the use of CladT beyond its initial courses of treatment will maximise the benefits of this treatment, especially early in the course of MS when suppression of focal inflammation in the CNS is a clinical priority to limit MS disease progression.

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...

Disease-modifying therapies in managing disability worsening in paediatric-onset multiple sclerosis: a longitudinal analysis of global and national registries

High-efficacy disease-modifying therapies have been proven to slow disability accrual in adults with relapsing-remitting multiple sclerosis. However, their impact on disability worsening in paediatric-onset multiple sclerosis, particularly during the early phases, is not well understood. We evaluated how high-efficacy therapies influence transitions across five disability states, ranging from minimal disability to gait impairment and secondary progressive multiple sclerosis, in people with paediatric-onset multiple sclerosis. Longitudinal data were obtained from the international MSBase registry, containing data from people with multiple sclerosis from 151 centres across 41 countries, and the Italian Multiple Sclerosis and Related Disorders Register, containing data from people with multiple sclerosis from 178 Italian multiple sclerosis centres. People younger than 18 years at the onset of multiple sclerosis symptoms were included, provided they had a confirmed diagnosis of relapsing-remitting multiple sclerosis and at least four Expanded Disability Status Scale (EDSS) scores recorded within 12-month intervals. The primary outcome was the time to change in disability state: minimal disability (EDSS scores 0, 1·0, and 1·5), mild disability (EDSS scores 2·0 and 2·5), moderate disability (EDSS scores 3·0 and 3·5), gait impairment (EDSS scores ≥4·0), and clinician diagnosed secondary progressive multiple sclerosis. A multi-state model was constructed to simulate the natural course of multiple sclerosis, modelling the probabilities of both disability worsening and improvement simultaneously. The impact of high-efficacy disease-modifying therapies (alemtuzumab, cladribine, daclizumab, fingolimod, mitoxantrone, natalizumab, ocrelizumab, rituximab, or autologous haematopoietic stem cell transplantation) and low-efficacy disease-modifying therapies (dimethyl fumarate, glatiramer acetate, interferon beta, or teriflunomide), compared with no treatment, on the course of disability was assessed. Apart from recruitment, individuals with lived experience of multiple sclerosis were not involved in the design and conduct of this study. A total of 5224 people (3686 [70·6%] female and 1538 [29·4%] male) with mean age at onset of multiple sclerosis 15·24 years (SD 2·52) were included. High-efficacy therapies reduced the hazard of disability worsening across the disability states. The largest reduction (hazard ratio 0·41 [95% CI 0·31-0·53]) was observed in participants who were treated with high-efficacy therapies while in the minimal disability state, compared with those remained untreated. The benefit of high-efficacy therapies declined with increasing disability. Young people with minimal disability who received low-efficacy therapy also experienced a reduced hazard (hazard ratio 0·65 [95% CI 0·54-0·77]) of transitioning to mild disability, in contrast to those who remained untreated. Treatment of paediatric-onset relapsing-remitting multiple sclerosis with high-efficacy therapy substantially reduces the risk of reaching key disability milestones. This reduction in risk is most pronounced among young people with minimal or mild disability when treatment began. Children with relapsing-remitting multiple sclerosis should be treated early with high-efficacy therapy, before developing significant neurological impairments, to better preserve their neurological capacity. National Health and Medical Research Council, Australia; MSBase Foundation Fellowship; MS Australia Postdoctoral Fellowship.

Efficacy and safety of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing remitting multiple sclerosis (StarMS): protocol for a randomised controlled trial

IntroductionAutologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial,...

Prognostic indicators for hospitalization and ICU admission in people with multiple sclerosis and COVID-19: an analysis of the COVID-19 in MS global data sharing initiative dataset

Objectives: To analyze the symptoms and severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (pwMS) on disease-modifying therapies using data from the COVID-19 in multiple sclerosis (MS) Global Data Sharing Initiative dataset. Methods: The open-access COVID-19 in MS Global Data Sharing Initiative dataset was obtained through credentialed access using PhysioNet. The variables analyzed included BMI, symptoms of COVID-19, age, current use of disease-modifying therapy (DMT), efficacy of DMT, comorbidities, hospitalization status, and type of MS. A linear regression analysis was completed. Data analysis and visualization were completed using STATA v15, R-Studio v1.1.447, Python v3.8, and its associated libraries, including NumPy, Pandas, and Matplotlib. Results: A total of 1141 participants were included in the analysis. 904 women and 237 men were diagnosed with MS. Among the pwMS included in the study; 208 (19.54%) had a suspected infection with COVID-19 and only 49 (5.25%) were confirmed. Any COVID-19 symptom was present in 360 individuals. The commonly reported DMT agents included dimethyl fumarate (12.71%) and fingolimod (10.17%). 101 in total (8.85%) reported not using any DMT. Factors associated with hospitalization and/or admission to the ICU included having any comorbidity (P=0.01), neuromuscular disorder (P=0.046), hypertension (P=0.005), chronic kidney disease (P&lt;0.001), and immunodeficiency (P=0.003). The type of MS, the duration of the disease, and high-efficacy DMT therapy did not have a statistically significant influence on hospitalization. Conclusion: This study underscores the importance of comorbidities, especially neuromuscular disorders, hypertension, chronic kidney disease, and immunodeficiencies, as possible prognostic indicators for worse outcomes of COVID-19 in pwMS. On the contrary, the type of MS, the duration of the disease, and the efficacy of disease-modifying therapy did not significantly affect the severity of the symptoms of COVID-19 in this cohort.

Cost and effectiveness of autologous haematopoietic stem cell transplantation and high-efficacy disease-modifying therapies in relapsing-remitting multiple sclerosis.

Autologous haematopoietic stem cell transplantation (AHSCT) is a highly effective one-off treatment for relapsing-remitting multiple sclerosis (RR-MS), potentially representing an optimal front-loading strategy for costs. Exploring cost/effectiveness of AHSCT and high-efficacy disease-modifying treatments (HE-DMTs) in RR-MS, estimating costs at our centre in Italy, where National Health Service (NHS) provides universal health coverage. Costs (including drugs, inpatient/outpatient management) for treatment with AHSCT and HE-DMTs were calculated as NHS expenditures over 2- and 5-year periods. Cost-effectiveness for each treatment was estimated as "cost needed to treat" (CNT), i.e. expense to prevent relapses, progression, or disease activity (NEDA) in one patient over n-years, retrieving outcomes from published studies. Costs of AHSCT and HE-DMTs were similar over 2years, whereas AHSCT was cheaper than most HE-DMTs over 5years (€46 600 vs €93 800, respectively). When estimating cost-effectiveness of treatments, over 2years, mean CNT of HE-DMTs for NEDA was twofold that of AHSCT, whereas it was similar for relapses and disability. Differences in CNT were remarkable over 5years, especially for NEDA, being mean CNT of HE-DMTs €382 800 vs €74 900 for AHSCT. AHSCT may be highly cost-effective in selected aggressive RR-MS. Besides priceless benefits for treated individuals, cost-savings generated by AHSCT may contribute to improving healthcare assistance at a population level.

Recent trends in disease-modifying therapy use and associated sickness absence and disability pension among people with multiple sclerosis in Sweden

Background: Disease-modifying therapies (DMTs) have led to improved health and work productivity among people with multiple sclerosis (PwMS). Objectives: To describe trajectories of recent DMT use and their association with sickness absence and/or disability pension (SADP) among PwMS in Sweden. Methods: A longitudinal register–based study was conducted among 1395 PwMS with treatment start in 2014/2015. While DMT use over 5 years was assessed using sequence analysis resulting in four clusters, a 7-year (Y−2 toY4) trend of SADP was analyzed using zero-inflated negative binomial regression. Results: Four clusters of DMT use trajectories were identified: long-term non-high-efficacy (483, 34.6%), long-term high-efficacy (572, 41%), escalation (221, 15.8%), and discontinuation (119, 8.5%). Progressive MS and higher expanded disability status scale scores were associated with the escalation, long-term high-efficacy, or discontinuation clusters. PwMS in the long-term high-efficacy and escalation clusters had higher likelihood of being on SADP. However, PwMS initiating high-efficacy DMTs demonstrated steeper decline in SADP than others. Conclusion: Using sequence analysis, this study showed recent DMT use trajectories among PwMS where initiation of high-efficacy DMTs has become more common. The trend of SADP was stable and lower in those using non-high-efficacy DMTs and larger improvements were shown in those initiating high-efficacy DMTs.

University education facilitates uptake of disease-modifying therapies for multiple sclerosis: A community-based study using the UK MS Register.

Higher education is associated with better job opportunities and higher income. Herein, the impact of education on the uptake of disease-modifying therapies (DMTs) for multiple sclerosis (MS) in a publicly funded health care system was examined using the UK MS Register. All adult participants with relapsing remitting MS diagnosed between 2008 and 2021 were included. Those without data regarding their education levels were excluded. Binary, multinomial and Cox regression models were used to examine the association between education levels and uptake of DMTs. A total of 6317 participants fulfilled all inclusion and exclusion criteria. A total of 1826/2923 (62%) participants with a university education were treated with DMTs, compared to 1788/3394 (53%) participants with school/diploma received DMTs with an odds ratio of 1.318 (1.178-1.473). Participants with a university education were more likely to be treated with both moderate- and high-efficacy DMTs, compared to others, with odds ratios of 1.227 (1.087-1.385) and 1.545 (1.325-1.802), respectively. University education was also a positive predictor for faster initiation of DMTs, and, importantly, higher-efficacy DMTs. In a publicly funded health care system, despite intended equality of access, university education was associated with a higher uptake of DMTs.

Association between demographics, socioeconomics, and disease-related factors and the perception of stigma in people with MS.

Stigma is prevalent among individuals with chronic diseases, such as multiple sclerosis (MS) and those with comorbid mental health disorders, but its associated factors are poorly understood. To investigate the prevalence and correlates of stigma in people living with MS. We analyzed data from the MS Partners Advancing Technology and Health Solutions (MS PATHS) network, which collected patient information and outcomes during routine clinic visits. We used a multinomial logistic regression model to examine the cross-sectional association between stigma and demographic, socioeconomics, and MS-related factors. We included 11,634 participants. The mean Neuro-QoL stigma T-score was 47.2 ± 8.6, and 17.7% of participants were classified as having moderate to severe stigma using established cutoffs. Multinomial logistic regression models suggest that higher disability levels, progressive form of the disease, shorter duration of the disease, and unemployment were associated with higher stigma while being male, married, undergoing treatment with high-efficacy disease-modifying therapies (DMTs), and being from European MS centers were associated with lower stigma perception. Disability levels, measured by Patient-Determined Disease Steps (PDDS), had the strongest independent association with stigma. Stigma remains a relevant issue for people living with MS. Factors, such as physical and cognitive disability, DMT, and employment status may influence the severity of perceived stigma.

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.

Long-term clinical outcomes in patients with multiple sclerosis who are initiating disease-modifying therapy with natalizumab compared with BRACETD first-line therapies.

Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance. Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate). This retrospective analysis utilized data from MSBase to create a matched population allowing comparison of first-line natalizumab to first-line BRACETD. This study included patients who initiated treatment either with natalizumab or a BRACETD DMT within 1 year of MS diagnosis and continued treatment for ⩾6 months, after which patients could switch DMTs or discontinue treatment. Patients had a minimum follow-up time of ⩾60 months from initiation. A subgroup analysis compared the natalizumab group to patients in the BRACETD group who escalated therapy after 6 months. Outcomes included unadjusted annualized relapse rates (ARRs), time-to-first relapse, time-to-first confirmed disability improvement (CDI), and time-to-first confirmed disability worsening (CDW). After 1:1 propensity score matching, 355 BRACETD patients were matched to 355 natalizumab patients. Patients initiating natalizumab were less likely to experience a relapse over the duration of follow-up, with ARRs [95% confidence interval (CI)] of 0.080 (0.070-0.092) for natalizumab patients and 0.191 (0.178-0.205) for BRACETD patients (p < 0.0001). A Cox regression model of time-to-first relapse showed a reduced risk of relapse for natalizumab patients [hazard ratio (95% CI) of 0.52 (0.42-0.65); p < 0.001] and a more favorable time-to-first CDI. The risk of CDW was similar between groups. The subgroup analysis showed an increased relapse risk as well as a significantly higher risk of CDW for BRACETD patients. Early initiation of natalizumab produced long-term benefits in relapse outcomes in comparison with BRACETD, regardless of a subsequent escalation in therapy.

Contemporary Patterns of High-Efficacy Disease Modifying Therapy Use in Korean Patients with Relapsing-Remitting Multiple Sclerosis

Background: Despite the compelling evidence indicating that early initiation of high-efficacy disease modifying therapies (DMTs) is more effective in controlling disease activity and preventing long-term disability in relapsing-remitting multiple sclerosis (RRMS), there is a scarcity of data regarding the implementation of such treatments in Korea. This study aimed to investigate the actual proportion of patients requiring high-efficacy DMT when disease activity is closely monitored.Methods: We conducted a retrospective analysis of medical records of 104 patients with RRMS who developed their disease after 2015 at the National Cancer Center in Korea. The status of no evidence of disease activity-3 (NEDA-3) was defined as no relapse, disability progression, or active lesions in annual magnetic resonance imaging evaluations.Results: Among 104 RRMS patients, 95 started with moderate-efficacy DMT, and nine with high-efficacy DMT. Of patients, 51% showed disease activity despite moderate-efficacy DMT, and prompting 41% to escalate high-efficacy DMT with a median time to switch of 20 months. Following the switch to a high-efficacy DMT, NEDA-3 was maintained in 82% of patients for a median of 27 months (interquartile range: 22, 45). Among the nine patients initially on high-efficacy DMT, no patient exhibited any signs of disease activity after median 34 months of treatment. The majority of patients experienced no significant side effects of high-efficacy DMT.Conclusion: The study showed a significant number of patients requiring escalation to high-efficacy DMT within a few years of treatment initiation with moderate-efficacy DMT, emphasizing the importance of early intervention strategies in managing the patients.

Contemporary Patterns of High-Efficacy Disease Modifying Therapy Use in Korean Patients with Relapsing-Remitting Multiple Sclerosis

Background: Despite the compelling evidence indicating that early initiation of high-efficacy disease modifying therapies (DMTs) is more effective in controlling disease activity and preventing long-term disability in relapsing-remitting multiple sclerosis (RRMS), there is a scarcity of data regarding the implementation of such treatments in Korea. This study aimed to investigate the actual proportion of patients requiring high-efficacy DMT when disease activity is closely monitored.Methods: We conducted a retrospective analysis of medical records of 104 patients with RRMS who developed their disease after 2015 at the National Cancer Center in Korea. The status of no evidence of disease activity-3 (NEDA-3) was defined as no relapse, disability progression, or active lesions in annual magnetic resonance imaging evaluations.Results: Among 104 RRMS patients, 95 started with moderate-efficacy DMT, and nine with high-efficacy DMT. Of patients, 51% showed disease activity despite moderate-efficacy DMT, and prompting 41% to escalate high-efficacy DMT with a median time to switch of 20 months. Following the switch to a high-efficacy DMT, NEDA-3 was maintained in 82% of patients for a median of 27 months (interquartile range: 22, 45). Among the nine patients initially on high-efficacy DMT, no patient exhibited any signs of disease activity after median 34 months of treatment. The majority of patients experienced no significant side effects of high-efficacy DMT.Conclusion: The study showed a significant number of patients requiring escalation to high-efficacy DMT within a few years of treatment initiation with moderate-efficacy DMT, emphasizing the importance of early intervention strategies in managing the patients.