Background:
Siponimod-related lymphopenia in real-world clinical practice has implications for dose adjustment and infection risk.
Objective:
To characterise siponimod-related lymphopenia in people ...with secondary progressive multiple sclerosis (pwSPMS).
Methods:
This is a retrospective cohort of 188 pwSPMS. The development of grade 4 lymphopenia was interrogated with Kaplan–Meier survival analysis and binary logistic regression.
Results:
Lymphopenia develops soon after commencing siponimod. In total, 15 (8.5%) of 176 experienced grade 4 lymphopenia at 1 month after initiation. There were no clinically significant associations between patient characteristics and development of grade 4 lymphopenia.
Conclusion:
Grade 4 lymphopenia can occur soon after siponimod initiation and cannot be predicted.
Background:
People with MS (pwMS) have had higher rates of anxiety and depression than the general population before the COVID-19 pandemic, placing them at higher risk of experiencing poor ...psychological wellbeing during the pandemic.
Objective:
To assess mental health and its social/lifestyle determinants in pwMS during the first wave of the outbreak in the United Kingdom.
Methods:
This is a community-based, prospective longitudinal cohort and cross-sectional case–control online questionnaire study. It includes 2010 pwMS from the UK MS Register and 380 people without MS.
Results:
The Hospital Anxiety and Depression Scale scores of pwMS for anxiety and depression during the outbreak did not change from the previous year. PwMS were more likely to have anxiety (using General Anxiety Disorder-7) and/or depression (using Patient Health Questionnaire-9) than controls during the outbreak (OR: 2.14, 95% CI: 1.58–2.91). PwMS felt lonelier (OR: 1.37, 95% CI: 1.04–1.80) reported worse social support (OR: 1.90, 95% CI: 1.18–3.07) and reported worsened exercise habits (OR: 1.65, 95% CI: 1.18–2.32) during the outbreak than controls.
Conclusion:
Early in the pandemic, pwMS remained at higher risk of experiencing anxiety and depression than the general population. It is important that multidisciplinary teams improve their support for the wellbeing of pwMS, who are vulnerable to the negative effects of the pandemic on their lifestyle and social support.
The assessment of treatment response is a crucial step for patients with relapsing-remitting multiple sclerosis on disease-modifying therapies (DMTs). We explored whether a scoring system developed ...within the MAGNIMS (MRI in Multiple Sclerosis) network to evaluate treatment response to injectable drugs can be adopted also to oral DMTs.
A multicentre dataset of 1200 patients who started three oral DMTs (fingolimod, teriflunomide and dimethyl fumarate) was collected within the MAGNIMS network. Disease activity after the first year was classified by the 'MAGNIMS' score based on the combination of relapses (0-≥2) and/or new T2 lesions (<3 or ≥3) on brain MRI. We explored the association of this score with the following 3-year outcomes: (1) confirmed disability worsening (CDW); (2) treatment failure (TFL); (3) relapse count between years 1 and 3. The additional value of contrast-enhancing lesions (CELs) and lesion location was explored.
At 3 years, 160 patients experienced CDW: 12% of them scored '0' (reference), 18% scored '1' (HR=1.82, 95% CI 1.20 to 2.76, p=0.005) and 37% scored '2' (HR=2.74, 95% CI 1.41 to 5.36, p=0.003) at 1 year. The analysis of other outcomes provided similar findings. Considering the location of new T2 lesions (supratentorial vs infratentorial/spinal cord) and the presence of CELs improved the prediction of CDW and TFL, respectively, in patients with minimal MRI activity alone (one or two new T2 lesions).
Early relapses and substantial MRI activity in the first year of treatment are associated with worse short-term outcomes in patients treated with some of the oral DMTs.
Randomised controlled trials (RCTs) play an important role in multiple sclerosis (MS) research, ensuring that new interventions are safe and efficacious before their introduction into clinical ...practice. Trials have been evolving to improve the robustness of their designs and the efficiency of their conduct. Advances in digital and mobile technologies in recent years have facilitated this process and the first RCTs with decentralised elements became possible. Decentralised clinical trials (DCTs) are conducted remotely, enabling participation of a more heterogeneous population who can participate in research activities from different locations and at their convenience. DCTs also rely on digital and mobile technologies which allows for more flexible and frequent assessments. While hospitals quickly adapted to e-health and telehealth assessments during the COVID-19 pandemic, the conduct of conventional RCTs was profoundly disrupted. In this paper, we review the existing evidence and gaps in knowledge in the design and conduct of DCTs in MS.
ObjectivesTo capture the complexities and unique experience of a newly formed multidisciplinary and multicentre research team developing and deploying a COVID-19 study and to identify lessons ...learnt.DesignCo-autoethnographic study.SettingStaff at two UK academic institutions, a national charity and two major UK hospitals.ParticipantsResearchers, clinicians, academics, statisticians and analysts, patient and public involvement representatives and national charity.MethodsThe sampling frame was any content discussed or shared between research team members (emails, meeting minutes, etc), standard observational dimensions and reflective interviews with team members. Data were thematically analysed.ResultsData from 34 meetings and >50 emails between 17 March and 5 August 2020 were analysed. The analysis yielded seven themes with ‘Managing our stress’ as an overarching theme.ConclusionsMutual respect, flexibility and genuine belief that team members are doing the best they can under the circumstances are essential for completing a time-consuming study, requiring a rapid response during a pandemic. Acknowledging and managing stress and a shared purpose can moderate many barriers, such as the lack of face-to-face interactions, leading to effective team working.
•Risk of SARS-CoV-2 infection in pwMS on ocrelizumab compared to the general population is increased despite mass vaccination.•Risk of SARS-CoV-2 infection in pwMS on fingolimod compared to the ...general population is increased despite mass vaccination.•The risk remains the same as the general population for pwMS on other MS therapies after mass vaccination.
Contradicting assumptions have been made about the effectiveness of SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) receiving immunomodulatory disease-modifying therapies (DMTs) based on the quantification of humoral and cellular immune responses. This study aimed to understand changes in the risk of SARS-CoV-2 infection among the total population of patients receiving MS DMTs in England following mass vaccination.
This is a retrospective analysis of national data collected prospectively and longitudinally. National Health Service (NHS) England and NHS Improvement (NHSE/I) hold prescribing data on all commissioned MS DMTs in England. United Kingdom Health Security Agency (UKHSA) has been collecting data on all registered SARS-CoV-2 test results, including polymerase chain reaction and rapid antigen tests. All patients receiving MS DMTs were identified using NHSE/I datasets. All patients receiving MS DMTs with SARS-CoV-2 infection (i.e., positive test) from March 2020 to August 2021 were identified by merging NHSE/I and UKHSA datasets. Similar data for the general population were captured using publicly available datasets of the United Kingdom government. The incidence rate ratios (IRR) of SARS-CoV-2 infection among patients receiving MS DMTs compared to the general population during the pre-vaccination (November 2020 to January 2021) and post-vaccination (June to August 2021) periods were calculated.
A mean (standard deviation) of 41,208 (4,301) patients received an MS DMT in England during each month from March 2020 to August 2021. The IRR (95% confidence interval) of infection in patients taking ocrelizumab versus the general population increased from 1.13 (0.97–1.31) during the pre-vaccination period to 1.79 (1.57–2.03) during the post-vaccination period. For patients on fingolimod, it increased from 0.87 (0.73–1.02) to 1.40 (1.20–1.63) during the same periods. There were no significant changes for patients on other MS DMTs.
SARS-CoV-2 vaccines offer less protection against infection to patients taking ocrelizumab or fingolimod, who have an impaired immune response to vaccines, than the general population. These findings will have implications for vaccination policies.
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