Patient-reported impact of myasthenia gravis in the real world: findings from a digital observational survey-based study (MyRealWorld MG).

OBJECTIVES: This study aims to explore the impact of myasthenia gravis (MG) - in terms of treatments, side effects, comorbidities, psychological health and work or study- in the real world from a patient perspective. DESIGN AND PARTICIPANTS: This is a prospective, observational, digital, longitudinal study. Adults diagnosed with MG residing in the USA, Japan, Germany, the UK, Italy, Spain or Canada were eligible to participate in the study. There were no other exclusion criteria. Participants used a bespoke smartphone application to confirm eligibility, provide consent and enter data about their MG into a profile, a tracker to record MG-related events and a series of patient-reported outcome instruments. 1693 participants completed at least 1 survey and were included in this analysis. RESULTS: Results are presented as a percentage of respondents to each survey question. The study population was largely female (69% of 1586 respondents), with an average age of 49.9 years (SD 14.8). In the previous 12 months, 83.7% of 1412 respondents confirmed that they had received one or more routine treatments for MG, and 67.1% of 255 respondents confirmed that they had experienced a side effect in the previous month. Commonly experienced comorbidities reported by 966 respondents were thyroid problems, hypertension and anxiety, experienced by 37.5%, 31.4% and 28.0% of respondents, respectively.According to 889 respondents to the Hospital Anxiety and Depression Scale survey, 52.7% and 43.2% had a score indicative of at least mild anxiety and mild depression, respectively. Of 257 respondents, 33.0% reported experiencing a work or study impact in the past month. CONCLUSIONS: This analysis of baseline characteristics of the MyRealWorld MG study population indicates that, despite current treatments, patients experience notable burden. Further scheduled analyses will develop a longitudinal picture of MG burden. TRIAL REGISTRATION NUMBER: NCT04176211.

Patient-reported burden of myasthenia gravis: baseline results of the international prospective, observational, longitudinal real-world digital study MyRealWorld-MG.

OBJECTIVES: Myasthenia gravis (MG) is a rare, chronic, autoimmune neuromuscular disease which can affect functional and mental aspects of health and health-related quality of life (HRQoL). This study aims to obtain detailed knowledge of the impact of MG on HRQoL in a broad population from the perspective of the patient. DESIGN: Prospective, observational, digital, longitudinal real-world study. SETTING: Adult patients with MG from seven countries (USA, Japan, Germany, UK, Italy, Spain and Canada) downloaded a mobile application onto their phones and entered data about themselves and their MG. OUTCOME MEASURES: Data was collected using the following general and disease-specific patient-reported outcome measurements: EuroQol 5 Domains Health-Related Quality of Life Questionnaire (EQ-5D-5L), Myasthenia Gravis Activities of Daily Living (MG-ADL), Myasthenia Gravis Quality of Life 15-item revised scale (MG-QoL-15r), Hospital Anxiety and Depression Scale (HADS) and Health Utilities Index III (HUI3). Patients were categorised by their self-assessed Myasthenia Gravis Foundation of America (MGFA) class (I-V). RESULTS: Baseline results of 841 participants (mean age 47 years, 70% women) are reported . The distribution across the MGFA classes was: 13.9%, 31.0%, 38.1%, 15.5% and 1.6% for classes I-V. The MGFA class was a strong predictor of all aspects of HRQoL, measured with disease-specific and with generic instruments. The domains in which patients with MG most frequently mentioned problems were usual activities, anxiety and depression, tiredness, breathing and vision. The mean total MG-ADL Score was positively associated with increasing MGFA classes: 2.7, 4.4, 6.3 and 8.4 for MGFA classes I-IV. Mean baseline EQ-5D-5L utility was also associated with MGFA classes and was 0.817, 0.766, 0.648 and 0.530 for MGFA class I-IV. CONCLUSIONS: MG has a large impact on key aspects of health and HRQoL. The impact of this disease increases substantially with increasing disease severity.

Patient-reportedimpact of myasthenia gravis in the real world: protocol for a digital observational study (MyRealWorld MG).

INTRODUCTION: Myasthenia gravis (MG) is a rare, chronic, autoimmune disease, mediated by immunoglobulin G antibodies, which causes debilitating muscle weakness. As with most rare diseases, there is little patient-reported data with which to understand and address patient needs. This study explores the impact of MG in the real world from the patient perspective. METHODS AND ANALYSIS: This is a 2-year prospective, observational, digital, longitudinal study of adults with MG, resident in the following countries: the USA, Japan, Germany, France, the UK, Italy, Spain, Canada and Belgium. The planned sample size is 2000. Recruitment will be community based, via patient advocacy groups, social media and word of mouth. Participants will use a smartphone application (app) to check eligibility, provide consent and contribute data. Planned data entry is as follows: (1) personal profile on enrollment-covering demographics, MG characteristics and previous care; (2) monthly event tracker-current treatments, healthcare visits, treatment-related adverse events, productivity losses; (3) monthly selection of validated generic and disease-specific patient-reported outcomes instruments: EQ-5D-5L, Myasthenia Gravis Activities of Daily Living, Myasthenia Gravis Quality of Life 15-item revised scale, Hospital Anxiety and Depression Scale and Health Utilities Index III. Analyses are planned for when the study has been running in most countries for approximately 6, 12, 18 and 24 months. ETHICS AND DISSEMINATION: The study protocol has been reviewed and granted ethics approval by Salus IRB for participants resident in the following countries: Germany, the UK and the US. Local ethics approval is being sought for the following study countries: Belgium, Canada, France, Italy, Japan and Spain. Study results will be communicated to the public and participants via conference presentations and journal publications, as well as regular email, social media and in-application communication. TRIAL REGISTRATION NUMBER: NCT04176211.

Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder, characterized by a low platelet count (<100 × 109 /L) in the absence of other causes associated with thrombocytopenia. In most patients, IgG autoantibodies directed against platelet receptors can be detected. They accelerate platelet clearance and destruction, inhibit platelet production, and impair platelet function, resulting in increased risk of bleeding and impaired quality of life. Efgartigimod is a human IgG1 antibody Fc-fragment, a natural ligand of the neonatal Fc receptor (FcRn), engineered for increased affinity to FcRn, while preserving its characteristic pH-dependent binding. Efgartigimod blocks FcRn, preventing IgG recycling, and causing targeted IgG degradation. In this Phase 2 study, 38 patients were randomized 1:1:1 to receive four weekly intravenous infusions of either placebo (N = 12) or efgartigimod at a dose of 5 mg/kg (N = 13) or 10 mg/kg (N = 13). This short treatment cycle of efgartigimod in patients with ITP, predominantly refractory to previous lines of therapy, was shown to be well tolerated, and demonstrated a favorable safety profile consistent with Phase 1 data. Efgartigimod induced a rapid reduction of total IgG levels (up to 63.7% mean change from baseline), which was associated with clinically relevant increases in platelet counts (46% patients on efgartigimod vs 25% on placebo achieved a platelet count of ≥50 × 109 /L on at least two occasions, and 38% vs 0% achieved ≥50 × 109 /L for at least 10 cumulative days), and a reduced proportion of patients with bleeding. Taken together, these data warrant further evaluation of FcRn antagonism as a novel therapeutic approach in ITP.

The management of pregnancy in paroxysmal nocturnal haemoglobinuria on long term eculizumab.

In Paroxysmal nocturnal haemoglobinuria (PNH), pregnancy is associated with increased maternal and foetal complications to such an extent that the condition has been considered relatively contra-indicated in PNH. Eculizumab has revolutionized the treatment of PNH. We evaluate its use in pregnancy to date. We report on seven patients exposed to eculizumab at different stages of pregnancy including the first two patients to receive the drug from conception to delivery. There was no evidence of complement blockade from cord blood samples taken at delivery. Eculizumab appears safe to use in this setting and is likely to prevent many of the complications usually observed.

Delayed valproic acid toxicity: a retrospective case series.

STUDY OBJECTIVE: We estimate how often an initially undetectable or nontoxic valproic acid (VPA) concentration misrepresents the potential toxicity of an acute VPA overdose. METHODS: All patients followed up by the San Diego and San Francisco Divisions of the California Poison Control System between January 1997 and June 1999 with a documented serum VPA concentration of 120 microg/mL or greater at any time were identified through a search of poison center databases. Cases involving patients who had serial VPA concentrations and an initial VPA concentration that was unmeasurable or less than 100 microg/mL were also identified. The methods of decontamination, clinical outcomes, highest measured concentration, and times after ingestion of the initial and highest measured concentration of VPA were determined by means of chart review for these cases. RESULTS: Of the 173 patients identified with VPA concentrations of 120 microg/mL or greater, 21 (12.1%) had a detectable initial concentration not in the toxic range, and 5 (2.9%) had initial concentrations of less than the limit of detection. These 26 cases involved acute ingestion of VPA preparations. Four of these 26 patients were discharged to home or to a psychiatric facility after the initial results were obtained. CONCLUSION: Delayed toxicity might occur in patients after an acute overdose of enteric-coated VPA. Initial serum VPA concentrations might be misleading. Serial measurements documenting declining VPA concentrations or prolonged observation are recommended to determine whether a patient is medically safe for discharge or psychiatric placement.