Efficacy and safety of rozanolixizumab in patients with muscle-specific tyrosine kinase autoantibody-positive generalised myasthenia gravis: a subgroup analysis of the randomised, double-blind, placebo-controlled, adaptive phase III MycarinG study.

Background: Muscle-specific tyrosine kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) is a rare and frequently severe subtype of gMG. Objectives: To assess the efficacy and safety of rozanolixizumab in the subgroup of patients with MuSK Ab+ gMG in the MycarinG study. Design: A randomised, double-blind, placebo-controlled phase III study. Methods: Patients with acetylcholine receptor (AChR) Ab+ or MuSK Ab+ gMG (aged ⩾18 years, Myasthenia Gravis Foundation of America Disease Class II-IVa, Myasthenia Gravis Activities of Daily Living [MG-|ADL] score ⩾3.0 [non-ocular symptoms], Quantitative Myasthenia Gravis score ⩾11.0) were randomly assigned (1:1:1) to receive once-weekly subcutaneous infusions of rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg or placebo for 6 weeks, followed by an 8-week observation period. Randomisation was stratified by AChR and MuSK autoantibody status. The primary study endpoint was change from baseline to Day 43 in MG-ADL score. Treatment-emergent adverse events (TEAEs) were also assessed. Results: Overall, 200 patients were randomised, of whom 21 had MuSK Ab+ gMG and received rozanolixizumab 7 mg/kg (n = 5), 10 mg/kg (n = 8) or placebo (n = 8). In patients with MuSK Ab+ gMG, reductions from baseline to Day 43 in MG-ADL scores were observed: rozanolixizumab 7 mg/kg least squares mean (LSM) change (standard error), -7.28 (1.94); 10 mg/kg, -4.16 (1.78); and placebo, 2.28 (1.95). Rozanolixizumab 7 mg/kg LSM difference from placebo was -9.56 (97.5% confidence interval: -15.25, -3.87); 10 mg/kg, -6.45 (-11.03, -1.86). TEAEs were experienced by four (80.0%), five (62.5%) and three (37.5%) patients with MuSK Ab+ gMG receiving rozanolixizumab 7 mg/kg, 10 mg/kg and placebo, respectively. No patients experienced serious TEAEs. No deaths occurred. Conclusion: This subgroup analysis of adult patients with MuSK Ab+ gMG enrolled in the MycarinG study supports the use of rozanolixizumab as an effective treatment option for patients with gMG who have MuSK autoantibodies. Trial registration: ClinicalTrials.gov: NCT03971422 (https://clinicaltrials.gov/study/NCT03971422); EU Clinical Trials Register: EudraCT 2019-000968-18 (https://www.clinicaltrials|register.eu/ctr-search/trial/2019-000968-18/GB).

Rozanolixizumab improved symptoms in people with anti-muscle-specific tyrosine kinase antibody-positive generalised myasthenia gravis in the MycarinG clinical study Myasthenia gravis is a rare, chronic autoimmune disease affecting the communication between nerves and muscles. People with the disease experience fluctuating muscle weakness and fatigue, leading to problems with mobility, speaking, swallowing and breathing. The disease is called generalised when muscles other than those that move the eyes and eyelids are affected. It is caused by antibodies that attack a person's own cells. Most people with the disease have antibodies against acetylcholine receptors (AChRs). However, some have antibodies against the muscle-specific tyrosine kinase (MuSK) protein and can experience more severe symptoms compared with people who have anti-AChR antibodies. Standard treatments for myasthenia gravis do not always work for people with anti-MuSK antibodies. The MycarinG study looked at whether rozanolixizumab was better than a placebo at treating the symptoms of adults with generalised myasthenia gravis and anti-AChR or anti-MuSK antibodies. Assessments measured disease severity and myasthenia gravis symptoms, such as physical fatigue, and how they affected daily activities. The study also looked at whether people receiving rozanolixizumab had any side effects. Here, we look at the group of people with anti-MuSK antibodies who took part in the MycarinG study. In total, 21 of the 200 people in the study had anti-MuSK antibodies. The symptoms of myasthenia gravis improved more in people with anti-MuSK antibodies who received rozanolixizumab than in those who received placebo. Common side effects with rozanolixizumab included headache, diarrhoea and feeling sick. No serious side effects were seen, and no patients died. The results show that rozanolixizumab is an effective treatment for people with generalised myasthenia gravis who have anti-MuSK antibodies. The results in this group of people are consistent with those seen in all people who took part in the study (with either antibody type).

Burden of acute symptomatic seizures in cerebral venous sinus thrombosis: A nationwide United States analysis.

INTRODUCTION: Acute symptomatic seizures (ASS) are seen in one-third of cerebral venous sinus thrombosis (CVT) cases either as the presenting symptom or shortly after diagnosis in the acute phase. The goal of our study was to assess the trends in recognition of ASS in CVT over the years and to determine factors predictive of ASS in the patients with CVT for early identification of candidates who would benefit from anti-seizure medications (ASM). MATERIALS AND METHODS: The Nationwide Inpatient Sample (NIS) database was accessed to identify adult inpatient admissions with a primary or secondary diagnosis of CVT. Comorbidities, complications, risk factors, and procedures pertaining to these hospitalizations were compared between CVT patients with and without ASS. RESULTS: A total of 53,710 CVT-related hospitalizations were identified, of which 18.1% of patients had a burden of ASS at presentation or subsequently during hospitalization. CVT patients with ASS had a longer average duration of hospitalization and higher overall morbidity and mortality. CONCLUSIONS: Our study showed ~one in five patients (18.1%) with CVT had ASS. ASS patients had higher odds of mortality and disability at discharge, requiring post-discharge rehabilitation care. It is crucial to identify risk factors of ASS in the CVT population to avoid future preventable revisit related to seizures. Additional research is required for risk stratification of patients with CVT for primary and secondary seizure prophylaxis and determining the appropriate choice and duration of ASM in these patients.

Stroke in young cannabis users (18-49 years): National trends in hospitalizations and outcomes.

BACKGROUND: Recent legalization of therapeutic and recreational cannabis use makes it imperative to have an insight into odds and trends in young-onset stroke-related hospitalizations among cannabis users (18-49 years). METHODS: The National Inpatient Sample dataset (2007-2014) was utilized to assess national trends, odds of young-onset stroke-related hospitalizations, and outcomes among cannabis users vs. nonusers using provided discharge weights, strata, and cluster design. The rates are described per 100,000 hospitalizations among cannabis users and non-users. RESULTS: A total of 3,307,310 hospitalizations were identified among young adults with current or previous cannabis use. Of these, 34,857 (1.1%) were related to young-onset stroke. A relative increase of 13.92% (553 in 2007 to 630 in 2014; ptrend < 0.001) in young-onset stroke admissions was reported among cannabis users. The odds of any stroke (OR 1.16, 95% CI 1.14-1.19, p < 0.001) and acute ischemic stroke (OR 1.41, 95% CI 1.31-1.51, p < 0.001) hospitalizations were considerably higher among cannabis users as compared to nonusers. In-hospital mortality rates were increasing (3.7% to 4.3%) among cannabis users whereas decreasing (7.7% to 5.9%) in nonusers from 2007 to 2014 (ptrend < 0.001). The mean length of stay and the hospitalization charges showed increasing trends in cannabis-related young-onset stroke admissions. There was an increasing trend in young-onset stroke admissions among male cannabis users (578 to 701; ptrend < 0.001) but not among females (516 to 457; ptrend = 0.14). The maximum rise in the young-onset stroke-related admissions was seen in African Americans (743 to 996; ptrend < 0.001). CONCLUSIONS: We identified rising trends and higher risk (16% higher of overall young-onset stroke, 41% higher of acute ischemic stroke) of stroke-related hospitalizations and worse outcomes among cannabis users aged 18-49 years from 2007 to 2014.