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 enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

• MeSH
• autoprotilátky krev   MeSH
• činnosti denního života MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• imunologické faktory terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• intravenózní imunoglobuliny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis * farmakoterapie   MeSH
• prospektivní studie MeSH
• receptory cholinergní * imunologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disorder with significant clinical implications, including life-threatening myasthenic crises and exacerbations. Understanding real-world treatment patterns, especially associated direct medical costs, is essential for the effective management of healthcare delivery. METHODS: We conducted a descriptive cohort study using health administrative claims data from the Czech Republic covering more than 1,500 prevalent MG patients. Data were analysed for healthcare resource utilization, medication costs, and hospitalization rates related to MG and its complications. RESULTS: Acetylcholine inhibitors and corticosteroids were widely prescribed, with 91.1% and 75.2% of patients receiving them at least once, respectively. Immunosuppressive therapy was given to 45.2% of patients. Myasthenic crises occurred in 2% of patients, with a mean hospitalization cost of 21,020 EUR, while exacerbations occurred in 9.2% of patients, with lower costs (5,951 EUR per hospitalization). Outpatient intravenous immunoglobulin and plasma exchange therapies incurred additional costs of 20,700 EUR and 18,206 EUR per person-year, respectively. The mean total cost per patient-year was 1,271 EUR, with significant cost differences among patients with different treatment patterns. CONCLUSION: This study offers real-world insights into the treatment patterns and associated direct medical costs of MG in the Czech Republic. Myasthenic crises and exacerbations pose considerable cost burdens, while outpatient therapies and common pharmacotherapies are less costly. These findings are vital for healthcare planning, economic evaluation, and resource allocation, potentially leading to enhanced patient care and outcomes.

• MeSH
• dospělí MeSH
• hospitalizace ekonomika   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myasthenia gravis * ekonomika   terapie   farmakoterapie   MeSH
• náklady na zdravotní péči MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Súčasná konvenčná liečba generalizovanej myasténie gravis (gMG) má rôzne úskalia - neskorší nástup účinku niektorých liečiv, výskyt nežiaducich účinkov limitujúcich samotnú liečbu aj kvalitu života pacienta, nedostatočná účinnosť u malej skupiny pacientov. Preto sa vyvíjajú liečivá cielene ovplyvňujúce časti imunitného systému, ktoré sú v jednoznačnej kauzálnej súvislosti s etiopatogenézou MG. Výhodou týchto liekov je ich vysoká účinnosť a dobrý bezpečnostný profil. Ako sľubná terapeutická možnosť sa javia aj inhibítory komplementu, ktorý sa uplatňuje pri etiopatogenéze MG s pozitivitou protilátok proti acetylcholínovému receptoru (AChR). V našej práci opisujeme mechanizmus účinku ekulizumabu a ravulizumabu, prezentujeme výsledky klinických štúdií a ich liekový profil.

The current conventional treatment of generalized myasthenia gravis (gMG) has various pitfalls - later onset of effect of some drugs, occurrence of adverse effects limiting the treatment itself and the patient's quality of life, lack of effectiveness in a small group of patients. Therefore, new drugs are being developed that specifically affect parts of the immune system that are in a clear causal connection with the MG etiopathogenesis. The advantage of these drugs is their high efficiency and good safety profile. Complement inhibitors, which are used in the etiopathogenesis of MG with positivity of antibodies against the acetylcholine receptor (AChR), also appear as a promising therapeutic option. In our work, we describe the mechanism of action of eculizumab and ravulizumab, present the results of clinical studies and their drug profile.

• Klíčová slova
• ravulizumab, ekulizumab,
• MeSH
• humanizované monoklonální protilátky * farmakologie   terapeutické užití   MeSH
• inhibitory komplementu * farmakologie   terapeutické užití   MeSH
• komplement C5 účinky léků   MeSH
• lidé MeSH
• myasthenia gravis * farmakoterapie   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Thymic neuroendocrine tumor as a cause of Cushing syndrome is extremely rare in children. CASE PRESENTATION: We report a case of a 10-year-old girl who presented with typical symptoms and signs of hypercortisolemia, including bone fractures, growth retardation, and kidney stones. The patient was managed with oral ketoconazole, during which she experienced adrenal insufficiency, possibly due to either cyclic adrenocorticotropic hormone (ACTH) secretion or concurrent COVID-19 infection. The patient underwent a diagnostic work-up which indicated the possibility of an ACTH-secreting pituitary neuroendocrine tumor. However, after a transsphenoidal surgery, the diagnosis was not confirmed on histopathological examination. Subsequent bilateral inferior petrosal sinus sampling showed strong indications of the presence of ectopic ACTH syndrome. Detailed rereading of functional imaging studies, including 18F-FDG PET/MRI and 68Ga DOTATOC PET/CT, ultimately identified a small lesion in the thymus. The patient underwent videothoracoscopic thymectomy that confirmed a neuroendocrine tumor with ACTH positivity on histopathological examination. CONCLUSION: This case presents some unique challenges related to the diagnosis, management, and treatment of thymic neuroendocrine tumor in a child. We can conclude that ketoconazole treatment was effective in managing hypercortisolemia in our patient. Further, a combination of functional imaging studies can be a useful tool in locating the source of ectopic ACTH secretion. Lastly, in cases of discrepancy in the results of stimulation tests, bilateral inferior petrosal sinus sampling is highly recommended to differentiate between Cushing disease and ectopic ACTH syndrome.

• MeSH
• Cushingův syndrom etiologie   diagnóza   chirurgie   MeSH
• dítě MeSH
• ektopický ACTH syndrom * diagnóza   chirurgie   MeSH
• ketokonazol terapeutické užití   MeSH
• lidé MeSH
• nádory brzlíku * komplikace   diagnóza   chirurgie   patologie   MeSH
• neuroendokrinní nádory * komplikace   diagnóza   chirurgie   patologie   MeSH
• thymektomie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

x

x

• Klíčová slova
• ekulizumab, Ravulizumab,
• MeSH
• humanizované monoklonální protilátky farmakologie   terapeutické užití   MeSH
• inaktivátory komplementu farmakologie   terapeutické užití   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• myasthenia gravis * farmakoterapie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: We recently described magnetic resonance imaging (MRI) features of children with transverse myelitis (TM) at first event with important and unique differences depending on the underlying disease entity. OBJECTIVE: To study the resolution of lesions over time in children with TM due to MOG-antibody associated disorders (MOGAD), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) or double seronegative TM. PATIENTS AND METHODS: In this prospective study, 78 children from 29 different medical centres with TM as part of MOGAD (n = 34), MS (n = 20), NMOSD (n = 5) and in double seronegative children (n = 19) were included. A grading system consisting of 4 grades (grade 0 = complete resolution; grade 3 = no resolution at all) was used to compare the degree of lesion resolution over time in the different disease entities. Time to lesion resolution was evaluated by Kaplan-Meier statistics and log-rank test. RESULTS: Significant differences of the interval between first MRI until resolution of lesions were observed between the four disease entities. The most rapid and complete resolution was seen in MOGAD, followed by double seronegative, MS and NMOSD. Median periods until total resolution (grade 0) were 191 days (MOGAD), 750 days (double seronegative), 1117 days (MS), while none of the patients with NMOSD reached a complete resolution during the observation period. The better prognosis of MOGAD compared to MS was independent of sex, age, oligoclonal bands and cell count in the multivariate Cox analysis (P < 0.001). CONCLUSION: Children with TM and antibodies to MOG show a faster resolution of radiological lesions compared to children with MS and NMOSD.

• MeSH
• autoprotilátky krev   MeSH
• dítě MeSH
• glykoprotein v myelinu oligodendrocytů imunologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mícha diagnostické zobrazování   patologie   MeSH
• mladiství MeSH
• následné studie MeSH
• neuromyelitis optica * diagnostické zobrazování   MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• roztroušená skleróza * diagnostické zobrazování   patologie   MeSH
• transverzální myelitida * diagnostické zobrazování   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

• Klíčová slova
• efgartigimod,
• MeSH
• injekce subkutánní MeSH
• klinická studie jako téma MeSH
• látky ovlivňující centrální nervový systém * farmakologie   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis * farmakoterapie   psychologie   MeSH
• telemedicína metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Therapeutic plasma exchange (TPE) is used as an effective treatment modality for a variety of autoimmune disorders. Apart from its desired effect of removing pathological blood components, it also can remove coagulation factors and drugs. Currently, there is an insufficient amount of information regarding the use of direct oral anticoagulants in this setting. In this article, we present a case report of a patient with myasthenia gravis and chronic anticoagulation with apixaban who underwent a series of TPE while continuing apixaban treatment. We observed that only 10% of daily dose was removed by the procedure and plasma levels of apixaban corresponded with expected range. TPE was not associated with shortened drug plasma half-life. We did not observe any significant alteration of apixaban pharmacokinetics during the period of TPE therapy, as well as no thrombotic or bleeding events. This case report supports the use of apixaban in patients treated by TPE, nevertheless, to firmly establish apixaban efficacy and safety profile in this clinical setting further research is needed.

• MeSH
• antikoagulancia aplikace a dávkování   škodlivé účinky   MeSH
• inhibitory faktoru Xa * aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis farmakoterapie   terapie   MeSH
• poločas MeSH
• pyrazoly * aplikace a dávkování   farmakokinetika   MeSH
• pyridony * aplikace a dávkování   MeSH
• senioři MeSH
• výměna plazmy * metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

BACKGROUND: The clinical heterogeneity of myasthenia gravis (MG), an autoimmune disease defined by antibodies (Ab) directed against the postsynaptic membrane, constitutes a challenge for patient stratification and treatment decision making. Novel strategies are needed to classify patients based on their biological phenotypes aiming to improve patient selection and treatment outcomes. METHODS: For this purpose, we assessed the serum proteome of a cohort of 140 patients with anti-acetylcholine receptor-Ab-positive MG and utilised consensus clustering as an unsupervised tool to assign patients to biological profiles. For in-depth analysis, we used immunogenomic sequencing to study the B cell repertoire of a subgroup of patients and an in vitro assay using primary human muscle cells to interrogate serum-induced complement formation. FINDINGS: This strategy identified four distinct patient phenotypes based on their proteomic patterns in their serum. Notably, one patient phenotype, here named PS3, was characterised by high disease severity and complement activation as defining features. Assessing a subgroup of patients, hyperexpanded antibody clones were present in the B cell repertoire of the PS3 group and effectively activated complement as compared to other patients. In line with their disease phenotype, PS3 patients were more likely to benefit from complement-inhibiting therapies. These findings were validated in a prospective cohort of 18 patients using a cell-based assay. INTERPRETATION: Collectively, this study suggests proteomics-based clustering as a gateway to assign patients to a biological signature likely to benefit from complement inhibition and provides a stratification strategy for clinical practice. FUNDING: CN and CBS were supported by the Forschungskommission of the Medical Faculty of the Heinrich Heine University Düsseldorf. CN was supported by the Else Kröner-Fresenius-Stiftung (EKEA.38). CBS was supported by the Deutsche Forschungsgemeinschaft (DFG-German Research Foundation) with a Walter Benjamin fellowship (project 539363086). The project was supported by the Ministry of Culture and Science of North Rhine-Westphalia (MODS, "Profilbildung 2020" [grant no. PROFILNRW-2020-107-A]).

• MeSH
• aktivace komplementu MeSH
• autoprotilátky * krev   imunologie   MeSH
• B-lymfocyty metabolismus   imunologie   MeSH
• dospělí MeSH
• fenotyp * MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis * krev   diagnóza   imunologie   metabolismus   MeSH
• proteom MeSH
• proteomika * metody   MeSH
• receptory cholinergní * imunologie   metabolismus   MeSH
• senioři MeSH
• shluková analýza MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Myasthenia gravis is a chronic antibody-mediated autoimmune disease disrupting neuromuscular synaptic transmission. Informative biomarkers remain an unmet need to stratify patients with active disease requiring intensified monitoring and therapy; their identification is the primary objective of this study. We applied mass spectrometry-based proteomic serum profiling for biomarker discovery. We studied an exploration and a prospective validation cohort consisting of 114 and 140 anti-acetylcholine receptor antibody (AChR-Ab)-positive myasthenia gravis patients, respectively. For downstream analysis, we applied a machine learning approach. Protein expression levels were confirmed by ELISA and compared to other myasthenic cohorts, in addition to myositis and neuropathy patients. Anti-AChR-Ab levels were determined by a radio receptor assay. Immunohistochemistry and immunofluorescence of intercostal muscle biopsies were employed for validation in addition to interactome studies of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3). Machine learning identified ITIH3 as potential serum biomarker reflective of disease activity. Serum levels correlated with disease activity scores in the exploration and validation cohort and were confirmed by ELISA. Lack of correlation between anti-AChR-Ab levels and clinical scores underlined the need for biomarkers. In a subgroup analysis, ITIH3 was indicative of treatment responses. Immunostaining of muscle specimens from these patients demonstrated ITIH3 localization at the neuromuscular endplates in myasthenia gravis but not in controls, thus providing a structural equivalent for our serological findings. Immunoprecipitation of ITIH3 and subsequent proteomics lead to identification of its interaction partners playing crucial roles in neuromuscular transmission. This study provides data on ITIH3 as a potential pathophysiological-relevant biomarker of disease activity in myasthenia gravis. Future studies are required to facilitate translation into clinical practice.

• MeSH
• autoprotilátky krev   MeSH
• biologické markery * krev   metabolismus   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• myasthenia gravis * krev   diagnóza   patologie   metabolismus   MeSH
• proteomika metody   MeSH
• receptory cholinergní imunologie   metabolismus   MeSH
• sekreční inhibitory proteinas krev   MeSH
• senioři MeSH
• strojové učení MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH