Objective: To explore the feasibility of classical (CH50) and alternative (AH50) complement pathway activity as potential biomarkers for treatment guidance and monitoring during therapy with ravulizumab in patients with generalized myasthenia gravis (gMG) and compare these to therapeutic drug monitoring under eculizumab. Methods: In this prospective, exploratory real‐world study CH50 and AH50, eculizumab and ravulizumab blood levels were assessed in patients with acetylcholine‐receptor‐antibody (AChR‐ab) positive gMG. Patients were either pretreated with eculizumab or C5‐inhibitor naïve. Samples were collected before the next infusion (end‐of‐dose). Laboratory data were correlated with patient‐reported subjective duration of the ravulizumab effect. Results: Overall, 61 patients were enrolled. At the end of their respective dosing interval, median AH50 levels were more strongly suppressed with eculizumab than with ravulizumab (1% [0%–2%] versus 5% [3%–9%]; Cohen's d 2.2 [95% CI 1.5–2.8]). Patients who discontinued ravulizumab due to insufficient effects ( n = 19; 33%) had higher median AH50 levels than those who continued (7% [4%–13%] versus 5% [3%–8%]; Cohen's d −0.9 [95% CI −1.3 to −0.4]). In 81% ( n = 46) of patients, the therapeutic effect of ravulizumab diminished before the subsequent infusion after the standard 8‐week interval. Higher AH50 levels were correlated with earlier symptom recurrence. Interpretation: Our results indicate potential differences in the ability of eculizumab and ravulizumab to suppress complement pathway activity through their respective dosing intervals. Additionally, higher AH50 levels might be a potential biomarker to predict poor therapy response and faster wearing off of ravulizumab's effect. However, these findings need to be validated in large multicenter studies.

Background: Myasthenia gravis (MG) is rare, chronic autoimmune disorder of the neuromuscular junction that requires specialized care and often lifelong treatment, facing challenges due to its rarity and the limited availability of specialists. Telemedical solutions in specialized centers hold considerable promise in bridging this gap by increasing access to this care to a broader patient population in a timely manner. However, there is no research regarding interventional remote care solutions in the field of MG to date. Objective: This study aimed to assess the feasibility and usability among patients with MG and specialists of a telemedicine platform, tailored to patients with MG and designed to facilitate remote monitoring, treated in a specialized center. Methods: The telemedicine platform consisted of an app for patients and a web-based portal for physicians. Over a period of 3 months, 30 patients continuously monitored their vital parameters through external devices, including a digital spirometer and a wearable (activity tracker). Furthermore, patients completed 7 different patient-reported outcome measures (PROMs) through the app at predefined intervals. Specialists could review this monitoring data and adjust therapy as necessary. In addition, communication between patients and physicians was facilitated through a chat module. Feasibility was evaluated by total adherence rates for completing PROMs within the app, alongside the collection of spirometry and wearable data. Furthermore, user satisfaction was assessed among both patients with MG and physicians at the end of study. Results: Total adherence rates ranged from 74.3% (1830/2464) to 97.9% (327/334) across all data types, with the highest adherence observed for PROMs (1139/1179, 96.6%), followed by spirometry (293/334, 87.7%) and wearables (1830/2261, 80.9%). Notably, patients wore the wearable longer than required by protocol and conducted a higher number of spirometry measurements during the study than required per protocol (median 20 h/d [IQR 15-24] vs 14 h/d and median 49 [IQR 15-59] measurements vs 11 measurements, respectively). Technical issues and discomfort with wearables were factors affecting lower adherence in some patients. The System Usability Scale yielded a median score of 85 indicating “excellent usability.” In addition, results from a more detailed user evaluation questionnaire showed high levels of user satisfaction among both patients and health care professionals across diverse categories, including their experience of the care program, communication, and evaluation of the program. Conclusions: Remote monitoring of patients with MG through the telemedical platform demonstrated good feasibility and acceptability, as evidenced by above-average adherence rates and user satisfaction for both patients and physicians. The majority of patients wanted to continue using the app. These findings highlight the potential for user-friendly digital tools to enhance care for patients with MG, although addressing technical challenges and ensuring patient comfort with wearables are essential for optimal implementation. Further research involving larger cohorts and longer study duration is warranted to validate these findings.

Introduction: Generalized myasthenia gravis (gMG) may progress to life‐threatening myasthenic crises (MC) requiring mechanical ventilation. Standard therapy includes intravenous immunoglobulins (IVIg), plasmapheresis (PLEX), immunoadsorption (IA), and high‐dose corticosteroids. This study aimed to evaluate the real‐world effectiveness of complement‐inhibitors (C5‐I) in patients refractory to the standard treatment of MC (termed therapy‐refractory MC). Methods: This multicentre, retrospective study included patients with acetylcholine‐receptor‐antibody positive (AChR‐ab+) gMG experiencing MC or severe exacerbations (MGFA IVb/V) treated with eculizumab or ravulizumab in the intensive or intermediate care unit (ICU/IMC). The primary outcome was the proportion of patients discharged from ICU/IMC within six weeks after C5‐I initiation (German Clinical Trials Registry; DRKS00032104). Results: Among 17 identified cases, seven had thymoma‐associated MG (TAMG) and 10 had late‐onset MG; median age was 77 years. Five patients required non‐invasive and 12 invasive ventilation; nine underwent tracheotomy. Therapies included IVIg, PLEX, IA, and corticosteroids. Rituximab was added in two cases. Twelve patients received eculizumab and five ravulizumab. Median hospitalization before C5‐I initiation was 32 days (IQR 22–50) and median ICU‐stay was 17 days (IQR 4.5–35) thereafter. Fourteen patients (82%) reached the primary outcome. Two patients died due to bacterial sepsis; no meningococcal infection was observed. Conclusion: In MC or severe exacerbations insufficiently responsive to standard treatment with IVIg and PLEX/IA, add‐on C5‐I therapy may represent an effective therapeutic approach. Importantly, TAMG, a subtype typically excluded from interventional trials yet often requiring more intensive therapy, also demonstrated clinical improvement. These findings warrant further systematic evaluation of C5‐I as adjunctive therapy for AChR‐ab+ therapy‐refractory MC.

ObjectivesLipoprotein receptor-related protein 4 antibody-positive myasthenia gravis (LRP4-Ab-positive MG) is a rare serologic subgroup with poorly defined clinical phenotype. This study investigat...

Die Myasthenia gravis wird durch eine autoantikörpervermittelte Übertragungsstörung an der neuromuskulären Endplatte hervorgerufen. Leitsymptom ist eine belastungsabhängige Muskelschwäche. Diagnostisch haben der Nachweis von typischen Autoantikörpern und die elektrophysiologische Untersuchung einen hohen Stellenwert. Symptomatische und immunmodulierende medikamentöse Therapien stehen zur Verfügung, für bestimmte Patienten auch die Thymektomie. Die Prognose wird durch myasthene Krisen bestimmt, die mit einer erhöhten Mortalität einhergehen. Article published online: 05 March 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

INTRODUCTION: Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune diseases of the neuromuscular junction resulting in fatigable muscle weakness. Rituximab (RTX) is used to treat patients refractory to standard immunosuppression, but evidence for its efficacy remains inconsistent. Here, we analyzed real-world data on the clinical course and side effects of RTX in MG and LEMS patients. METHODS: This was a single-center study of all patients diagnosed with MG (n=64) or LEMS (n=5) treated with RTX from 2011 until 2021. Outcomes of RTX treatment were recorded retrospectively with Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS), number of rescue therapies, myasthenic crises, and steroid dose at 1-year and 2-year follow-ups. RESULTS: MGFA-PIS improved at both 1-year (y) and 2-y follow-up compared with baseline. Incidence rates of rescue therapies per 100 person-months (95% CI) decreased from 15.0 (11.8–18.8) at baseline to 7.5 (4.7–12.3) at 1-y and 4.3 (2.5–7.8) at 2y-follow-up. The number of patients without myasthenic crises within one year increased from baseline (49, 86.0%) to 1y-follow-up (55, 96.5%). Median (IQR) daily steroid dose decreased from 10 (5– 22.5) mg/d at baseline to 4 (0–10) mg/d at 1y-follow-up, and to 2.5 (0–10) mg/d at 2y-follow-up. CONCLUSION: This study indicates that RTX was associated with a stabilized clinical course and decreased steroid use in patients with autoimmune myasthenic syndromes, including those with thymoma-associated MG. Our data suggest that therapeutic benefit is apparent within the first year of treatment and is maintained through two years.