Vanood, Aimen

Background: Radiologically Isolated Syndrome (RIS) is defined as incidentally found MRI abnormalities that are radiographically indistinguishable from multiple sclerosis (MS) and is considered a presymptomatic disease state of MS. Age <37 years, infratentorial or spinal cord lesions, gadolinium-enhancing lesions on index imaging, and positive cerebrospinal fluid oligoclonal bands have been identified as risk factors for conversion to MS. There are no existing guidelines regarding the role of disease-modifying therapy (DMT) in RIS patients. Objective: The objective of this study was to critically assess the current evidence regarding the impact of initiating DMT for patients with RIS on the time to first clinical attack of MS. Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, medical librarian, and content experts in the field of neuroimmunology. Results: A multicenter, prospective, randomized, double-blind, placebo-controlled trial was chosen for critical appraisal. This trial examined the impact of treatment with dimethyl fumarate (DMF) versus placebo on the risk of conversion from RIS to MS over a 96-week study period. Patients in the DMF arm were found to have an 82% reduction in risk of clinical attack. DMF patients also had a smaller number of new/newly enlarging T2 hyperintense lesions compared with placebo. No subgroup analyses were performed to elucidate risk factors for conversion. Conclusions: While initiation of DMT in RIS does appear to reduce the time to first clinical attack of MS, the risk factors that should prompt initiation of DMT in this patient population require further study.

Abstract Background Erenumab is a monoclonal antibody that targets the calcitonin gene‐related peptide (CGRP) receptor and is approved for the preventative treatment of migraine in adults. CGRP is involved in the regulation of vasomotor tone under physiologic and pathologic conditions, including hypertension. While there has not been evidence of hypertension in preclinical models or clinical trials, post‐marketing data suggest erenumab may be associated with hypertension. This led to a warning in the United States Food and Drug Administration prescribing information for erenumab. Objective To determine the frequency of worsening blood pressure (BP) after initiation of erenumab in patients with migraine and how this is associated with hypertension. Methods This is an observational retrospective cohort study evaluating patients at a tertiary headache or neurology department. Systolic and diastolic BPs were compared between the initial visit prior to initiation of erenumab, and follow‐up visit while on erenumab. Worsening BP was defined as moving from a lower stage to a higher stage of BP, as defined by the American Heart Association. Serious adverse vascular events were also recorded. Results A total of 335 patients were included in the final analysis (mean [SD] age of 45.7 [14.40] years, 83.9% [281/335] female). At baseline, 20.9% (70/335) of patients had a prior diagnosis of hypertension. The median (interquartile range) time to follow‐up appointment from initial appointment was 20.5 (13.3–35.3) weeks. The mean (SD) BP at baseline was systolic 124.7 (15) mmHg and diastolic 77 (11) mmHg, and at follow‐up was systolic 124.0 (15) mmHg and diastolic 77.8 (9) mmHg. Overall, 23.3% (78/335) of all patients had worsening BP, whereas 13/225 (3.9%) patients had improvement in their BP. Patients with atrial fibrillation were more likely to develop worsening BP (odds ratio, 4.9, 95% confidence interval 1.12–21.4; p = 0.035). There was no association between worsening BP and pre‐existing hypertension, sex, body mass index, or age. One patient had non‐ST elevation myocardial infarction attributed to a hypertensive emergency while on erenumab. Conclusion We found that 23.3% of patients initiated on erenumab may have developed worsening BP, suggesting the need for BP monitoring in patients initiated on erenumab.