Safety and effectiveness of disease-modifying therapies after switching from natalizumab.

INTRODUCTION: One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined. OBJECTIVE: The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity. METHODS: This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity. RESULTS: Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression (p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p < 0.001, and 66.6% vs. 24.0%, p < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod (p < 0.001). CONCLUSION: Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity.

COVID-19 vaccination in people with multiple sclerosis, real-life experience.

BACKGROUND: Vaccination against the severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) virus is recommended in multiple sclerosis (MS) to reduce the risk of complications from Coronavirus disease 2019 (COVID-19) infection. These vaccines were not investigated in people with MS (PWMS). OBJECTIVE: This study aimed to report the short-term safety of the COVID-19 vaccines among PWMS. METHODS: Pfizer-BioNTech mRNA (BNT162b2) vaccine and Oxford-Astra Zenecaa chimpanzee adenovirus-vectored (ChAdOx1 nCoV-19) vaccine have been approved to be used in Kuwait since December 2021. PWMS registered in Kuwait national registry were contacted by phone, WhatsApp, or through face-to-face interviews and were invited to complete our questionnaire. Demographic, clinical data, symptoms following the vaccine, worsening of pre-existing MS symptoms, and occurrence of relapse were recorded. RESULTS: Of the 820 PWMS, 647 completed the questionnaire. Between January 2021 and 31 August 2021, 383 (59.28%) PWMS received at least one dose of the approved vaccinations versus 63.4% of the general population on the same date. Their mean age was 36.82 + 8.80, and most of them, 247 (64.3%), were females. A total of 356 vaccinated cohorts (92.6%) were treated with disease-modifying therapies. Adverse events were reported by 261 (68.15%) subjects. One case of COVID-19 infection was encountered after the first dose of the BNT162b2 vaccine. Twenty-one (5.48%) cases reported worsening of pre-existing MS symptoms after the vaccine. Five patients (1.31%) reported relapse after the COVID-19 vaccine. The most common adverse events of the COVID-19 vaccine were pain at the injection site, fatigue, low-grade fever, and body ache; and resolved within one week. There was no significant association between use of disease modifying therapy (DMT) and COVID-19 vaccine adverse events. CONCLUSION: BNT162b2 and ChAdOx1 nCoV-19 are safe for PWMS. No increased risk of relapse activity or worsening of pre-existing MS symptoms.

Prevalence, severity, outcomes, and risk factors of COVID-19 in multiple sclerosis: An observational study in the Middle East.

A cross-sectional hospital records-based study was conducted to evaluate the prevalence, severity, outcomes, and identify demographic and clinical risk factors of coronavirus disease (COVID-19) in patients with MS. The study was conducted at multiple clinics in Oman, Kuwait, and the United Arab Emirates (UAE) from March 2020 to February 2021. The association of patient demographics, MS disease characteristics, and use of disease-modifying therapies with outcomes of COVID-19 illness were evaluated using odds ratio. A total of 134 MS patients with COVID-19 (prevalence rate of 3.7%) having a median age of 35.5 years were analyzed in the study. A majority (126 [94.0%]) of patients had mild COVID-19 illness and 122 (91.0%) made a full recovery, while 1 (0.7%) patient died. The median EDSS score reported in the study was low (1.0). Univariate regression analysis showed high EDSS scores, progressive MS disease, and use of anti-CD20 therapy such as rituximab as risk factors for moderate to severe COVID-19 requiring hospitalization. Comorbidities were associated with a higher risk of non-recovery from COVID-19 in both univariate and multivariate analyses. Age, sex, smoking history, and duration of MS did not show a significant association with severity or adverse COVID-19 disease outcome. Identification of risk factors can aid in improving the treatment and monitoring of pwMS and COVID-19.

Onabotulinumtoxin A Improves Psychological Aspects in Chronic Migraine Patients.

Background: Chronic migraine (CM) affects 5.4% of the Kuwaiti population. It is associated with significant headache-related disability, psychiatric comorbidity and reduced quality of life. The aim of this study is to assess the efficacy of Onabotulinumtoxin A on psychological aspects of chronic migraine patients. Methods: This prospective study over 36 months included chronic migraine patients in a tertiary headache center. Eligible patients met International Classification of Headache Disorders disorders-third edition, beta version (ICHD-III) revision criteria for chronic migraine. Patients with history of psychiatric or medical problems other than migraine disorders were excluded. Patients who received less than 4 injections cycles of Onabotulinumtoxin A were excluded. Identified patients received 155 units of Onabotulinumtoxin A quarterly according to the Phase III Research Evaluating Migraine Prophylaxis Therapy Trail (PREEMPT) protocol. Quality of life, the seven-item Generalized Anxiety Disorder (GAD-7) scores, the nine-item Patient Health Questionnaire (PHQ9), and the Pittsburgh Sleep Quality Index (PSQI) were collected before injection and at the end of the study. Mean comparison tests were performed using the independent sample t-test to assess the effects of Onabotulinumtoxin A on quality of life and comorbid symptoms of anxiety, depression, and quality of sleep. Results: The study identified 131 chronic migraine patients with a mean age of 44.92 years, mean disease duration of 12.20 years and a mean treatment sessions of 7.58. In their last visit, most of our sample showed improvement in quality of life (81%), GAD-7 (81%), PHQ9 (79%), and PSQ1 (76%). The mean score of patient satisfaction was 7.21. Onabotulinumtoxin A treatment for CM improved quality of life significantly (72.92 vs. 103.62; P < 0.0001). It was also associated with significant reduction in anxiety [GAD-7 (12.00 vs. 6.61; P < 0.0001)] and depression [PHQ-9 (17.91 vs. 12.52; P < 0.0001)] scores, as well as reduced difficulty in sleeping [PSQI (12.60 vs. 6.66; P < 0.0001)] at the last visit. Conclusion: Prophylactic Onabotulinumtoxin A treatment for CM was associated with significant improvement of quality of life, reduction in symptoms of anxiety and depression, as well as improved symptoms of poor sleep.