Reduction in grey matter atrophy in patients with relapsing multiple sclerosis following treatment with cladribine tablets

Background and purpose Measures of atrophy in the whole brain can be used to reliably assess treatment effect in clinical trials of patients with multiple sclerosis (MS). Trials assessing the effect of treatment on grey matter (GM) and white matter (WM) atrophy are very informative, but hindered by technical limitations. This study aimed to measure GM and WM volume changes, using a robust longitudinal method, in patients with relapsing MS randomized to cladribine tablets 3.5 mg/kg or placebo in the CLARITY study. Methods We analysed T1-weighted magnetic resonance sequences using SIENA-XL, from 0 to 6 months (cladribine, n = 267; placebo, n = 265) and 6 to 24 months (cladribine, n = 184; placebo, n = 186). Mean percentage GM and WM volume changes (PGMVC and PWMVC) were compared using a mixed-effect model. Results More GM and WM volume loss was found in patients taking cladribine versus those taking placebo in the first 6 months of treatment (PGMVC: cladribine: -0.53 vs. placebo: -0.25 [p = 0.045]; PWMVC: cladribine: -0.49 vs. placebo: -0.34 [p = 0.137]), probably due to pseudoatrophy. However, over the period 6 to 24 months, GM volume loss was significantly lower in patients on cladribine than in those on placebo (PGMVC: cladribine: -0.90 vs. placebo: -1.27 [p = 0.026]). In this period, volume changes in WM were similar in the two treatment arms (p = 0.52). Conclusions After a short period of pseudoatrophy, treatment with cladribine 3.5 mg/kg significantly reduced GM atrophy in comparison with placebo. This supports the relevance of GM damage in MS and may have important implications for physical and cognitive disability progression. © 2022 The Authors

Antibody response to SARS-CoV-2 vaccines in patients with relapsing multiple sclerosis treated with evobrutinib: A Bruton\u27s tyrosine kinase inhibitor

BACKGROUND: Evobrutinib is an oral, central nervous system (CNS)-penetrant and highly selective covalent Bruton\u27s tyrosine kinase inhibitor under clinical development for patients with relapsing multiple sclerosis (RMS). OBJECTIVE: To investigate the effect of evobrutinib on immune responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinated patients with RMS from a Phase II trial (NCT02975349). METHODS: A RESULTS: In the vaccinated subgroup, mean/minimum evobrutinib exposure pre-vaccination was 105.2/88.7 weeks. In total, 43 of 45 patients developed/increased S1/S2 IgG antibody levels post-vaccination; one patient\u27s antibody response remained negative post-vaccination and the other had antibody levels above the upper limit of detection, both pre- and post-vaccination. Most patients ( CONCLUSION: These results suggest evobrutinib, an investigational drug with therapeutic potential for patients with RMS, acts as an immunomodulator, that is, it inhibits aberrant immune cell responses in patients with RMS, while responsiveness to foreig

Summary of Research: Collaboration Between Healthcare Professionals and People with Multiple Sclerosis to Develop Communication Tools to Improve the Standard of Multiple Sclerosis Care

: This is a summary of a previously published paper: Joint Healthcare Professional and Patient Development of Communication Tools to Improve the Standard of MS Care. It describes a collaboration between people with multiple sclerosis (PwMS) and healthcare professionals (HCPs) to identify challenges in multiple sclerosis (MS) care and design tools to improve communication during consultations

Knowledge Is Power, but Is Ignorance Bliss? Optimising Conversations About Disease Progression in Multiple Sclerosis

Communication about multiple sclerosis (MS) disease progression between healthcare professionals (HCPs) and people with MS (PwMS) has historically been considered difficult, and attention to improving it has been neglected. However, a growing number of studies have shown that this is a key area to get right, since negative experiences can affect patient satisfaction, treatment adherence, and clinical outcomes. This article reports on a symposium at the European Charcot Foundation, 2018, led by a panel of leading clinicians and patient experts from MS in the 21st Century, who debated the benefits, drawbacks, and challenges of communicating about disease progression, for both HCPs and PwMS, and potential ways to optimise these discussions. PwMS' preferences and priorities regarding conversations about disease progression vary widely. While the majority want to have these conversations, some will be reluctant and/or emotionally unready. Communication therefore needs to be personalised, and HCPs should always be prepared to have such conversations in an appropriate and sensitive manner. Clinical information can be opaque for PwMS, so HCPs also need to use language that is clear, easily understandable, and patient-friendly. MS in the 21st Century is in the process of developing several resources and programmes to help improve disease progression communication between HCPs and PwMS.ISSN:2193-6536ISSN:2193-825

Summary of Research: Caregiver Involvement in MS: Duty or Disruption?

Abstract This Summary of Research summarizes a previously published discussion between people with multiple sclerosis (PwMS) and their caregivers and healthcare professionals (HCPs) about how to include caregivers in consultations and decisions about multiple sclerosis (MS) care. The aim of the discussion was to help HCPs to understand differences in these relationships so they can adapt the style of consultations to support everyone

Caregiver Involvement in MS: Duty or Disruption?

Abstract Multiple sclerosis (MS) is a complex condition with numerous physical, cognitive and emotional symptoms. These may necessitate significant, permanent lifestyle changes for people with multiple sclerosis (PwMS) and their caregivers and families, meaning it is important in contemporary neurological practice to consider including families and/or caregivers in the management of MS. However, existing evidence suggests that family involvement is not always beneficial; for example, it can exert either a strong positive or negative influence on the ability of PwMS to achieve optimal outcomes from their treatment and disease management. This paper, based on a live debate between neurologists and PwMS, examines the current perceptions on constructive involvement of families and caregivers in consultations for and management of MS, and reveals several areas where additional studies are warranted. Shared decision-making in MS has historically been a collaboration solely between healthcare professionals (HCPs) and PwMS, but PwMS are now more frequently being accompanied to appointments by a support person. This paper encourages HCPs to understand the dynamics between PwMS and their support person, and to individualize consultations and information accordingly. Family and caregiver involvement in the provision of care for PwMS needs to be for the benefit of, and at the discretion of, the PwMS. Support for families of PwMS, although important, may be more effectively and appropriately delivered through other channels outside of the clinical setting. Educating HCPs on the current patient experience to enable them to provide improved personalized care will ensure a mutualistic, patient-centred relationship with PwMS, which will help to optimize outcomes. Communication tools may also facilitate these interactions

Assessing the duration of EDSS improvement after a therapy start: A novel approach applied to the long-term extension of the PRISMS study

Background: In a chronic and progressive disease such as multiple sclerosis (MS), the improvement on Expanded Disability Status Scale (EDSS) can be a transient event. Therefore, estimating the prevalence of disability improvement over time, accounting both for improvement incidence and duration, is of interest. The aim of this study was to show the application of a simple estimator for the proportion of patients with sustained improvement over time using data from the long-term extension of the PRISMS trial. Methods: A total of 534 relapsing-remitting MS (RRMS) patients from the PRISMS trial were included. Patients with a baseline EDSS of 0 were excluded. Patients were randomized to placebo (n = 178), subcutaneous interferon beta-1a (sc IFN β-1a) 22 µg (n = 181) or sc IFN β-1a 44 µg (n = 175). At Year 2, patients receiving placebo were re-randomized to sc IFN β-1a 22 µg or 44 µg (delayed sc IFN β-1a) while patients receiving sc IFN β-1a 22 µg or 44 µg continued their initial regimen. Patients were followed up for over 7 years post-randomization. Disability improvement was defined as a 1-point decrease in EDSS from baseline confirmed at 6 months. Prevalence of improvement was estimated as difference of Kaplan-Meier (KM) estimators while the cumulative incidence of improvement was calculated using the standard KM curves. Results: No significant differences in cumulative incidence of EDSS improvement at 3 years between delayed sc IFN β-1a (20.3%) and sc IFN β-1a 22 µg (20.8%; p = 0.49) or 44 µg (21.3%; p = 0.33). When taking duration of improvement into account, the proportion of patients showing an improved condition after 3 years was 10.1% with delayed sc IFN β-1a, 11.3% with sc IFN β-1a 22 µg (p = 0.17) and 15.4% with sc IFN β-1a 44 µg (p = 0.037) that was substantially maintained over the long term. Conclusions: With the use of this new statistical methodology, it is possible to estimate the time to improvement as well as the duration of improvement, information that is better suited to describing a non-final outcome like disability improvement. In this case, early sc IFN β-1a 44 µg initiation had a greater proportion of patients with a sustained disability improvement over a long period of follow-up as compared to patients who had initially been randomized to placebo. In contrast, no significant differences on the cumulative incidence of improvement were observed

Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: The CLARITY and CLARITY Extension studies

Background: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study of patients with relapsing-remitting multiple sclerosis, treatment with cladribine tablets 3.5 mg/kg (CladT) significantly reduced the annualised relapse rate (ARR) versus placebo; this effect was sustained in CLARITY Extension, without further treatment. Objective: To assess the frequency and severity of relapses in patients treated with CladT versus placebo in CLARITY over 2 years and evaluate the durability of effect in patients who received no further treatment for 2 years in CLARITY Extension. Methods: In this post hoc analysis, ARRs were calculated for qualifying and all relapses, and qualifying and all severe relapses (i.e. requiring steroid treatment or leading to hospitalisation) in patients treated with CladT ( n = 433) and placebo ( n = 437) in CLARITY, and those from the CladT group who received placebo in CLARITY Extension ( n = 98). Results: At Month 6, Year 1 and Year 2, patients receiving CladT had a significantly lower risk of qualifying or all relapses (all p < 0.0001), and qualifying or all severe relapses (all p < 0.005), compared with placebo. This effect was sustained in CLARITY Extension without further treatment. Conclusion: The results show durable efficacy of cladribine tablets 3.5 mg/kg for reducing frequency and severity of relapses in patients with relapsing-remitting multiple sclerosis. CLARITY: NCT00213135; CLARITY Extension: NCT0064153

Relapses in people with multiple sclerosis treated with cladribine tablets followed for up to 5 years: a plain language summary

What is this summary about? This is a summary of an article originally published in the Multiple Sclerosis Journal. The article presents the results from the CLARITY and CLARITY Extension studies, which looked at how well cladribine tablets work in treating people with multiple sclerosis (shortened to MS). Cladribine tablets are a medication approved for treating relapsing forms of MS. This study looked at how treatment with cladribine tablets affects the frequency and severity of relapses in people with MS. A relapse is when new symptoms develop or old symptoms return or get worse after a period of stability or improvement. What happened in the studies? In the CLARITY study, 870 people received either cladribine tablets (3.5 mg/kg, the approved dose) or placebo (a dummy pill). After the CLARITY study ended, some participants who received cladribine tablets chose to take part in a second study called the CLARITY Extension study. Of these participants, 98 were given placebo for 2 more years following an interval period of up to 10 months between participating in each study. What were the results? People with MS who were treated with cladribine tablets for 2 years in the CLARITY study had lower risks of any relapse compared with those given placebo. Participants taking placebo (after cladribine tablets) in the CLARITY Extension study experienced these same benefits, which continued for up to 3 more years after having received cladribine tablets in the CLARITY study. What do the results mean? Researchers concluded the recommended 2-year dosing of cladribine tablets may reduce the number and severity of relapses in people with MS for up to 5 years

Disease Progression in Multiple Sclerosis: A Literature Review Exploring Patient Perspectives

Purpose: Multiple sclerosis (MS) prognosis is often uncertain. This literature review considers patients’ understanding of, and perspectives on, MS progression to better comprehend the unmet needs of people with MS (PwMS), in order to improve treatment adherence and quality of life (QoL). Methods: Literature searches for peer-reviewed papers concerning patient perspectives on the progression of MS and comparable conditions, published between January 2000 and January 2020, were conducted. Results: Little qualitative evidence exists that examines PwMS’ perspectives on MS progression. The understanding and meaning ascribed to terms such as “disease progression” vary. Some PwMS find disease labels stigmatizing, confusing, and disconnected from reality. The lack of a clear definition of progression and discrepancies between PwMS and healthcare professional (HCP) perspectives may contribute to misunderstanding and poor communication. Patient descriptions of progression and relapses include symptoms in addition to those evaluated by standard severity and disability measures. Compared with HCPs, PwMS are still focused on relapse prevention but place higher priority on QoL and ascribe different relative importance to the causes of poor adherence to treatment plans. PwMS want to discuss progression and likely prognosis. Such communication needs to be personalized and delivered with sensitivity, at an appropriate time. Poor treatment adherence may arise from a lack of understanding and poor communication, particularly around treatment goals. The few studies that directly considered patient perspectives on the progression of comparable conditions supported and extended the perspectives of PwMS. Lack of adequate communication by HCPs was the most common theme. Conclusion: Patient perspectives on disease progression in MS and other chronic progressive conditions are under-investigated and under-reported. The limited evidence available highlights the importance of providing adequate information and effective HCP communication. While further studies are needed, the current evidence base offers information and insights that may help HCPs to enhance patient care, well-being, and treatment adherence