Vera Bril

University of Toronto | U of T · Department of Medicine

Background and Aims Small‐fibre neuropathy (SFN) is associated with glucose dysregulation, including impaired glucose tolerance (IGT) and type 2 diabetes (T2D). Corneal confocal microscopy (CCM) offers a non‐invasive tool to assess corneal nerve damage and dendritic cell density (DCD). In this study, we investigated corneal DCD in patients with SFN...

Background and Aims Hyaluronidase‐facilitated subcutaneous immunoglobulin (fSCIG) consists of subcutaneous human immunoglobulin G (IgG) 10% with recombinant human hyaluronidase (rHuPH20) and can be administered at the same dose and interval as intravenous IgG (IVIG). fSCIG recently received US approval as maintenance therapy for adults with chronic...

Introduction/Aims Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography‐purified IVIG; (IGIV‐C) in patients with generalized MG undergoing standard care. Methods Sixty‐two patients enr...

Background In the Phase 3 MycarinG (NCT03971422) study, one cycle (six once-weekly subcutaneous infusions) of rozanolixizumab 7mg/kg or 10mg/kg significantly improved myasthenia gravis (MG)-specific outcomes versus placebo. After MycarinG, patients could enrol in open-label extensions MG0004 (NCT04124965) or MG0007 (NCT04650854). We evaluated respo...

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...

Introduction/Aims The single simple question (SSQ), “What percentage of normal (0%–100%) do you feel regarding your disease?” has proven feasible and valid in assessing myasthenia gravis and a heterogeneous spectrum of neuropathies. This study explores the utility of the SSQ in axonal polyneuropathies (PNPs), encompassing diabetic neuropathy, and e...

Aim: Several studies have found subcutaneous (SC) and intravenous (IV) administration of similar drugs for long-lasting immunological and autoimmune diseases to have similar clinical effectiveness, meaning that what patients report they prefer is, or should be, a major factor in treatment choices. Therefore, it is important to systematically compil...

Backgrounds and objectives: Early use of immunosuppression has been suggested to prevent generalization of ocular myasthenia gravis (OMG), but high-quality evidence is limited in this regard. We examined whether treatment with prednisone and other immunosuppressants reduce the risk of generalization in OMG. Methods: This is a retrospective study...

Objective This study assesses the utility of jitter analysis with concentric needles to evaluate disease severity in myasthenia gravis (MG), correlate changes in jitter with clinical status as well as identify reasons for any discordance. Methods We performed a retrospective chart review of 82 MG patients and extracted data on demographics, MG sub...

Background: A key efficacy indicator in generalized myasthenia gravis (gMG) treatment is improvement in MG-ADL score. Minimal symptom expression (MSE, MG-ADL total score of 0 or 1) is explored as a novel proposed treatment target in gMG in the phase 3 study of intravenous efgartigimod, ADAPT, and its open-label extension, ADAPT+. Methods: Post hoc...

Background: Treatment of generalized myasthenia gravis (gMG) with reduced steroid dosages may minimize steroid-associated AEs. Corticosteroid dosage changes were not permitted during the 26-week, CHAMPION MG study of ravulizumab in adults with anti-acetylcholine receptor antibody-positive (AChRAb+) gMG. Participants who completed the study could re...

Objective To establish a simple electrophysiological scale for patients with distal symmetric axonal polyneuropathy, in order to promote standardized and informative electrodiagnostic reporting, and understand the complex relationship between electrophysiological and clinical polyneuropathy severity. Methods We included 76 patients with distal sym...

In the last decade, the landscape of treating autoimmune diseases has evolved with the emergence and approval of novel targeted therapies. Several new biological agents offer selective and target-specific immunotherapy and therefore fewer side effects, such as neonatal Fc receptor (FcRn)-targeting therapy. Neonatal Fc receptor-targeted therapies ar...

Introduction/Aims Whole‐body magnetic resonance neurography (MRN) is an imaging modality that shows peripheral nerve signal change in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We aimed to explore the diagnostic potential of whole‐body MRN and its potential as a monitoring tool after immunotherapy in treatment‐naïve CID...

Introduction: Transthyretin-related amyloidosis (ATTRv) is a progressive multisystem disorder, predominantly involving the peripheral nerve system (PNS) and heart. Quantification of small fiber damage may help guide treatment decisions, as amyloid deposits frequently affect those fibers early in disease course. Corneal confocal microscopy (CCM) is...

Objective ADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG). Methods ADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions...

Background and Objectives To evaluate in a phase 2 study the safety and efficacy of IV nipocalimab, a fully human, antineonatal Fc receptor monoclonal antibody, in patients with generalized myasthenia gravis (gMG). Methods Patients with gMG with inadequate response to stable standard-of-care (SOC) therapy were randomized 1:1:1:1:1 to receive eithe...

Introduction: Myasthenia gravis (MG) is an auto-immune disease characterized by fluctuating symptoms of muscle weakness and fatigue. Corticosteroids and corticosteroid-sparing broad-spectrum immunosuppression play a great role in the treatment of myasthenia gravis. However, debilitating side effects and long time to treatment effect highlight the...

Objectives To assess the safety, tolerability, and key pharmacodynamic effects of subcutaneous batoclimab, a fully human anti‐neonatal Fc receptor monoclonal antibody, in patients with generalized myasthenia gravis and anti‐acetylcholine receptor antibodies. Methods A Phase 2a, proof‐of‐concept, randomized, double‐blind, placebo‐controlled trial i...

Diabetic cranial neuropathies are much less prevalent than other forms of diabetic neuropathy, but the association of cranial neuropathies with diabetes is unequivocal. Overt cranial neuropathies affect less than 1% of diabetic patients, but there is a four to sevenfold increased risk of cranial neuropathies in diabetes. Cranial neuropathies of CNs...

Background Establish efficacy of rozanolixizumab (FcRn inhibitor) in generalised myasthenia gravis (gMG) across subgroups. Design/Methods The Phase 3 MycarinG study (MG0003/NCT03971422) randomised adults (MGFA Class II–IVa AChR/MuSK autoantibody-positive gMG) to weekly rozanolixizumab 7mg/kg, 10mg/kg or placebo for 6 weeks. The primary endpoint wa...

Background and purpose Generalized myasthenia gravis (gMG) is a rare, chronic, neuromuscular autoimmune disease mediated by pathogenic immunoglobulin G (IgG) autoantibodies. Patients with gMG experience debilitating muscle weakness, resulting in impaired mobility, speech, swallowing, vision and respiratory function. Efgartigimod is a human IgG1 ant...

Importance Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, Setting, and Participants NEURO-TTRansform was an open-label, single-group, phase 3 trial co...

Introduction Loss of muscle thickness can be demonstrated in a wide spectrum of neuromuscular disorders, while fasciculations are more frequent in amyotrophic lateral sclerosis (ALS). In the current study, we aimed to determine the sensitivity and specificity of quantitative sonographic assessment of muscle thickness and the presence of fasciculati...

Current guidelines for defining good outcomes in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) are predominately defined by experts. At present, we do not have a patient-anchored definition of what constitutes a “good” outcome. Our study aimed to assess the symptom burden of people living with CIDP, as well as satisfaction...

Background and purpose Double‐seronegative myasthenia gravis (dSNMG) is defined as myasthenia gravis (MG) without detectable or low affinity antibodies to acetylcholine receptor (AChR) and muscle‐specific kinase (MuSK). There are limited data on detailed clinical features and outcomes after treatment in dSNMG patients. The aim was to describe the c...

Myasthenia gravis (MG) is an autoimmune disorder characterized by autoantibodies specifically directed against proteins located within the postsynaptic membrane of the neuromuscular junction. These pathogenic autoantibodies can be reduced by therapies such as plasma exchange, IVIG infusions and other immunosuppressive agents. However, there are sig...

Introduction/aims: Dendritic cells (DCs) and their contacts with corneal nerves are described in animal models of nerve damage. Dendritic cell density (DCD) is a potential marker of immune activity in suspected small-fiber neuropathy (SFN). Here, we aim to evaluate the intra- and inter-rater reliability of DCD measurements in suspected SFN. Metho...

Objective To assess efficacy and safety of cyclical rozanolixizumab treatment, based on study MG0003 with the open-label extensions (OLEs) MG0004 (NCT04124965) and MG0007 (NCT04650854). Methods MG0004 was an OLE study of ≤52 weekly rozanolixizumab subcutaneous infusions. In MG0007, after an initial cycle, cycles were ‘symptom-driven’, administered...

Background: We have aimed to assess whether muscle thickness ultrasound (US) shows differences between patients with chronic inflammatory demyelinating polyneuropathy (CIDP), chronic axonal polyneuropathy (CAP), and other neuromuscular (NM) diseases compared to controls and to each other. Methods: We performed a cross-sectional study from Septem...

Introduction The patient acceptable symptom state (PASS) is a reliable way to characterize a patient’s satisfaction with their disease state in a “Yes”/“No” dichotomous manner. There is limited data on the time required to reach an acceptable state in Myasthenia Gravis (MG). We aimed to determine the time to reach a first PASS “Yes” response in pat...

Background and aims: ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse. Methods: ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial co...

Background: Efgartigimod, a human IgG1 antibody Fc-fragment, reduces IgG levels through neonatal Fc receptor blockade. Patients with anti-acetylcholine receptor antibody–negative (AChR-Ab–) generalized myasthenia gravis (gMG) comprise 15%-20% of the gMG population and have limited approved treatment options. We evaluated long-term safety and effica...

Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces IgG levels through FcRn blockade. A key efficacy indicator in the treatment of IgG autoantibody-mediated generalized myasthenia gravis (gMG) is improvement in MG-ADL score. Methods: The ADAPT phase 3 trial evaluated safety and efficacy of efgartigimod in patients with gMG, i...

Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total and pathogenic IgG autoantibody levels through FcRn blockade. ADAPT was a phase 3 trial evaluating efgartigimod in patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT could enroll in ADAPT+ (open-label extension). Methods: Efgartigimod (10 m...

Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces IgG autoantibody levels through FcRn blockade. This study reports safety of efgartigimod across IgG-mediated disorders. Methods: The safety of intravenous efgartigimod was evaluated in 204 efgartigimod-treated subjects with generalized myasthenia gravis (phase 3 ADAPT and 3-...

Background: The modified Toronto Clinical Neuropathy Score (mTCNS) is a valid and reliable scale for the diagnosis and staging of diabetic sensorimotor polyneuropathy (DSP). Objective: To determine the optimal diagnostic cut-off value of the mTCNS in diverse polyneuropathies. Methods: Demographics and mTCNS values were retrospectively extracte...

Background: Measuring health-related quality of life (HR-QOL) is vital for understanding the disease impact, but the complex relationship between clinical parameters and QOL remains unclear. The objective was to determine the demographic and clinical factors that influence the QOL in adults with inherited and acquired myopathies. Methods: The st...

Background: Generalised myasthenia gravis is a chronic, unpredictable, and debilitating autoimmune disease. New treatments for this disease are needed because conventional therapies have limitations, such as side-effects (eg, increased infection risk) or inadequate control of symptoms. Rozanolixizumab is a neonatal Fc receptor blocker that might p...

Treatment of acute exacerbations and refractory myasthenia gravis (MG) remains challenging despite advances in immunotherapy. Frequent use of plasmapheresis and immunoglobulins are associated with adverse events and strain on resources. The neonatal Fc receptor (FcRn) facilitates IgG recycling and FcRn antagonism enhances the degradation of IgG pat...

Importance: There are limited data regarding COVID-19 outcomes and vaccine uptake and safety among people with myasthenia gravis (MG). Objective: To investigate COVID-19-related outcomes and vaccine uptake among a population-based sample of adults with MG. Design, setting, and participants: This population-based, matched cohort study in Ontari...

Diabetic distal symmetric polyneuropathy (diabetic DSP) has variable clinical presentation that can complicate the diagnostic process. It is primarily identified by asymptomatic annual screening or from neuropathic symptoms. In this chapter, we present key considerations for findings on screening or clinical evaluation. First, identification of ris...

Background/objectives: Data on maintenance therapy with SCIg in myasthenia gravis (MG) is limited. We report on transitioning AChR Ab+ MG patients on stable IVIg regimens as part of routine clinical care to SCIg 1:1.2. Methods: This multi-center North American open-label prospective investigator-initiated study had two components: IVIg Screening...

Objective To evaluate the safety and efficacy of efgartigimod in patients with generalized myasthenia gravis (MG) enrolled in the ADAPT+ long-term extension study. Background Treatment with efgartigimod, a human IgG1 antibody Fc-fragment that blocks neonatal Fc receptor, resulted in clinically meaningful improvement (CMI) in MG-specific outcome me...

Amyloidosis is a rare protein misfolding disease caused by the accumulation of amyloid fibrils in various tissues and organs. There are different subtypes of amyloidosis, with light chain (AL) amyloidosis being the most common. Amyloidosis is notoriously difficult to diagnose because it is clinically heterogenous, no single test is diagnostic for t...

Objective To evaluate the relationship between clinical improvement in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores and the pharmacodynamic effects of IgG autoantibody lowering induced by nipocalimab in the Vivacity MG Phase 2 study. Background Nipocalimab is a fully human, aglycosylated, effectorless IgG1 anti-FcRn monoclonal anti...

Symptoms and disease pathophysiology of myasthenia gravis (MG) vary considerably with each patient, and their individual preferences and priorities add to the need for individualized treatment of this autoimmune disease. Research in MG has grown substantially in recent years. New treatments have the potential of being both effective and well tolera...

Background and objectives: Myasthenia gravis (MG) is an autoimmune disease characterized by dysfunction at the neuromuscular junction. Treatment frequently includes corticosteroids (CS) and intravenous immunoglobulin (IVIG). This study was conducted to determine if immune globulin (human), 10% caprylate/chromatography purified (IGIV-C) could facil...

Introduction In ADAPT, efgartigimod, a human IgG1 antibody Fc-fragment blocking neonatal Fc receptor, resulted in clinically meaningful improvement (CMI) in myasthenia gravis (MG)-specific measures. Patients completing ADAPT were eligible to enrol in ADAPT+ (open-label, 3-year extension study). Methods Efgartigimod, 10 mg/kg intravenous infusion a...

Aims To determine the relationship between renal hemodynamic function and neuropathy in adults with ≥50-years of type 1 diabetes (T1D) compared to nondiabetic controls. Methods Glomerular filtration rate (GFR, inulin), effective renal plasma flow (ERPF, p-aminohippurate), modified Toronto Clinical Neuropathy Score (mTCNS), corneal confocal microsc...

Autoimmune neuropathies are often treatable. First line immunotherapies include intravenous immunoglobulin (IVIG), plasma exchange and corticosteroids. However, nearly 15-30% of patients are either refractory, partially responsive or chronically dependent on these first line agents. Lack of full response leads to increased disability in addition to...

Background Hereditary transthyretin amyloidosis is an uncommon multisystem disorder caused by mutation of the transthyretin protein, leading to peripheral neuropathy often with autonomic features, cardiomyopathy, or a mixed phenotype. Multiple other organ systems can be involved with ophthalmologic, renal, hematologic, gastrointestinal, and/or geni...

Introduction/aim: Given the lack of information on safety of COVID-19 vaccination in myasthenia gravis (MG) patients, we aimed to review our experience after surveying patients, as part of routine clinical practise, to ensure that advice on safety is accurate. Methods: We performed a retrospective chart review of MG patients from the Prosserman...

Introduction: Myasthenia gravis (MG) is an antibody mediated disease where pathogenic antibodies interact with the acetylcholine receptor or other proteins at the post-synaptic neuromuscular junction. There is growing evidence that immunoglobulin infusions are beneficial for clinical exacerbations and chronic refractory disease and may be an optio...