Myasthenia gravis (MG) is a rare autoimmune disease characterised by exertion-induced muscle weakness that can lead to potentially life-threatening myasthenic crises. Detectable antibodies are directed against specific postsynaptic structures of the neuromuscular junction. MG is a chronic condition that can be improved through therapies, but to date, not cured. Standard treatment has been unchanged for decades and includes symptomatic treatment with acetylcholine-esterase inhibitors and disease-modifying treatment with steroids, steroid-sparing immunosuppressants and thymectomy. Overall, a relevant proportion of patients does not achieve a satisfactory clinical improvement under standard treatment. Additionally, long-term therapy with steroids can cause significant side effects and latency to clinical improvement with standard steroid-sparing immunosuppressants and after thymectomy can take months to years. In recent years, treatment of MG has changed fundamentally due to improved evidence from phase 3 trials and the regulatory approval of complement inhibitors and FcRn inhibitors as add-on treatment options. This provides new optimism for substantially more patients reaching minimal manifestation status and has led to a shift in treatment strategy with more targeted therapies being employed early in the course of the disease, especially in patients with high disease activity. In this focussed review, we provide an overview of the diagnosis, classification and standard treatment of MG, followed by data from randomised controlled trials on the modern drugs already available for therapy and those still in the final stages of clinical development. In the second part, we provide an overview of real-world data for already approved therapies and outline how the availability of new biologicals is changing both clinical decision-making and patient journey.

Acute hepatic porphyrias (AHP) can cause severe neurological symptoms involving the central, autonomic, and peripheral nervous system. Due to their relative rarity and their chameleon‐like presentation, delayed diagnosis and misdiagnosis are common. AHPs are genetically inherited disorders that result from heme biosynthesis enzyme deficiencies and comprise four forms: acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and ALA‐dehydratase porphyria (ALADP). Depending on the clinical presentation, the main differential diagnoses are Guillain‐Barré syndrome and autoimmune encephalitis. Red flags that could raise the suspicion of acute porphyria are neurological symptoms starting after severe (abdominal) pain, in association with reddish urine, hyponatremia or photodermatitis, and the presence of encephalopathy and/or axonal neuropathy. We highlight the diagnostic difficulties by presenting three cases from our neurological intensive care unit and give a comprehensive overview about the diagnostic findings in imaging, electrophysiology, and neuropathology.

Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab and the neonatal Fc receptor agonist efgartigimod have recently been approved for the treatment of acetylcholine receptor (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking. In a prospective, exploratory real-world study, we assessed clinical efficacy, safety, and biological effects of ravulizumab and efgartigimod treatment initiation. Myasthenia Gravis-Activities of Daily Living and Quantitative Myasthenia Gravis scores were used as clinical endpoints. Ab effector functions were determined by AChR-Ab-dependent complement activation and phagocytosis assays and systemic complement activation profiling. We observed similar moderate short-term efficacy of ravulizumab and efgartigimod in achieving clinical improvement. Ravulizumab reduced systemic terminal complement activation, but neither treatment showed significant effects on complement pathways proximal to C5 or functional capacities of AChR-Abs. Both treatment modalities were well tolerated with no serious adverse events reported. Clinical benefits obtained with ravulizumab and efgartigimod can be remarkably heterogeneous in daily clinical practice. Neither treatment relevantly changed effector functions of pathogenic AChR-Abs, supporting the concept that durable disease control in MG requires continuous administration of both fast-acting agents. This study provides Class III evidence that in AChR-Ab-positive patients with generalized MG, ravulizumab and efgartigimod provide comparable modest improvement in MG functional scales.

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.

Background: Myasthenia gravis (MG) is a rare disorder characterized by fluctuating muscle weakness with potential life‐threatening crises. Timely interventions may be delayed by limited access to care and fragmented documentation. Our objective was to develop predictive algorithms for MG deterioration using multimodal telemedicine data. Methods: In this 12‐week randomized controlled study, 30 MG patients recorded symptoms using patient‐reported outcome measures (PROMs) and patient‐performed measures via a mobile app, alongside data from wearables. MG deterioration was defined as a ≥ 3‐point worsening in the Quantitative Myasthenia Gravis score, occurrence of MG‐related hospitalization or exacerbation. A machine learning linear classifier was trained to predict deterioration and cross‐validated. The area under the receiver operator characteristic curve (AUROC) was calculated, accepting 1–2 false alarms (FAs) per week. Results: The model achieved the best predictive performance when using all input signals (AUROC 0.85 (95% confidence interval 0.77–0.91)) and remained stable across look‐back windows of 4–10 days. Model sensitivity was 0.65 (0.48–0.83) to 0.82 (0.60–1.00) (1 and 2 FAs per week, respectively). PROMs reflected worsening symptoms before deterioration; wearables alone showed higher AUROCs. Interpretation: Multimodal self‐monitoring via MyaLink predicted MG deterioration with good performance at acceptable FA rates. This approach may enable earlier clinical interventions of MG worsening. Trial Registration: The study was registered under the German Clinical Trial Registry (DRKS00029907)