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Background: Effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience. Objectives: Use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs. Methods: Retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR). Results: Cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54–6.32), 7.04 (4.16–11.93), and 6.52 (3.79–11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts. Conclusion: Cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators. [ABSTRACT FROM AUTHOR]

Background: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups. Objective: We evaluated sex-specific and onset phenotype–specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets. Methods: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype–specific MSSS matrices. We compared matrices using permutation analysis. Results: Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data (p > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix (p < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex. Conclusion: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts. [ABSTRACT FROM AUTHOR]

Objectives: To compare treatment persistence between two dosages of interferon b-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. Methods: Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon b-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon b-1a in either dosage (22 mg or 44 mg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. Results: Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as ‘‘lack of efficacy’’ (3.3% vs. 1.7%), ‘‘scheduled stop’’ (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 mg vs. 44 mg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. Conclusions: Treatment discontinuations were more common in interferon b-1a 22 mg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from ‘‘real-world’’ database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry. [ABSTRACT FROM AUTHOR]

What Is This Summary About?: Patient registries contain anonymous data from people who share the same medical condition. The MSBase registry contains information from over 80,000 people living with multiple sclerosis (MS) across 41 countries. Using information from the MSBase registry, the GLIMPSE (Generating Learnings In MultiPle SclErosis) study looked at real-life outcomes in 3475 people living with MS who were treated with cladribine tablets (Mavenclad ® ) compared with other oral treatments., What Were the Results?: Results showed that people treated with cladribine tablets stayed on treatment for longer than other treatments given by mouth. They also had fewer relapses (also called flare ups of symptoms) than people who received a different oral treatment for their MS., What Do the Results Mean?: The results provide evidence that, compared with other oral treatments for MS, cladribine tablets are an effective medicine for people living with MS.

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups., Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation., Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants., Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5)., Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear., Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms., Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores., Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p  < 0.001) and EDSS (β = 0.16, p  < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89, p  = 0.01) and EDSS (β = -0.06, p  < 0.001). Neither presentation was associated with changes in relapse risk., Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.

Background: The current best practice suggests yearly magnetic resonance imaging (MRI) to monitor treatment response in multiple sclerosis (MS) patients., Objective: To evaluate the current practice of clinicians changing MS treatment based on subclinical new MRI lesions alone., Methods: Using MSBase, an international MS patient registry with MRI data, we analysed the probability of treatment change among patients with clinically silent new MRI lesions., Results: A total of 8311 MRI brain scans of 4232 patients were identified. Around 26.9% (336/1247) MRIs with one new T2 lesion were followed by disease-modifying therapy (DMT) change, increasing to 50.2% (129/257) with six new T2 lesions. DMT change was twice as likely with new T1 contrast enhancing compared to new T2 lesions odds ratio (OR): 2.43, 95% confidence interval (CI): 2.00-2.96 vs OR: 1.26 (95% CI: 1.22-1.29). DMT change with new MRI lesions occurred most frequently with 'injectable' DMTs. The probability of switching therapy was greater only after high-efficacy therapies became available in 2007 (after, OR: 1.43, 95% CI: 1.28-1.59 vs before, OR: 0.98, 95% CI: 0.520-1.88)., Conclusion: MS clinicians rely increasingly on MRI alone in their treatment decisions, utilizing low thresholds (1 new T2 lesion) for optimizing MS therapy. This signals a shift towards no evidence of disease activity (NEDA)-3 since high-efficacy therapies became available.