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
- 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
Hrudní chirurgie je stále více ovlivňována rozvojem miniinvazivních přístupů, jež ovlivnily i chirurgii v oblasti předního mediastina. Dříve standardně používaný přístup k thymu cestou parciální sternotomie byl ve většině případů postupně nahrazen přístupem videothorakoskopickým. V posledních letech se celosvětově i v této oblasti začíná prosazovat roboticky asistovaná chirurgie. Cílem našeho sdělení je vytvořit ucelený přehled o výkonech v oblasti thymu včetně jejich indikací a dále se podělit o naše první zkušenosti s roboticky asistovanou chirurgií thymu. Na III. chirurgické klinice bylo od zahájení programu roboticky asistované chirurgie thymu provedeno tímto přístupem 23 thymektomií, z toho 17 výkonů pro thymom, 3 pro myasthenia gravis a 3 pro adenom příštítného tělíska lokalizovaný ve tkáni thymu. Z našich zkušeností i dostupných dat vyplývá, že doba hospitalizace, míra komplikací a výsledný efekt roboticky asistovaných výkonů jsou srovnatelné s VTS výkony, umožňují však miniinvazivní ošetření i u pacientů výrazně obézních a u pacientů s pokročilým nádorem thymu, kteří by byli jinak indikováni k otevřené thymektomii.
Thoracic surgery is increasingly influenced by the development of minimally invasive approaches which have also influenced surgery in the area of the anterior mediastinum. The previously standard approach to the thymus via partial sternotomy was gradually replaced by the videothoracoscopic approach in most cases. In recent years, robotically assisted surgery has been gaining ground worldwide in this area, as well. The aim of our paper is to provide a comprehensive overview of procedures in the field of the thymus, including their indications, and to share our first experience with robot-assisted thymus surgery. At the 3rd Department of Surgery, since the start of the robot-assisted thymus surgery program, 23 thymectomies have been performed using this approach, of which 17 were performed for thymoma, 3 for myasthenia gravis, and 3 for parathyroid adenoma localized in thymus tissue. From our experience and the available data, it follows that the length of hospitalization, the rate of complications and the resulting effect of robot-assisted procedures is comparable to VTS procedures; however, the robot-assisted surgery also allows for mini-invasive treatment even in significantly obese patients and in patients with advanced thymic tumors who would otherwise be indicated for open thymectomy.
- MeSH
- lidé MeSH
- myasthenia gravis diagnóza imunologie patologie terapie MeSH
- nádory brzlíku chirurgie klasifikace MeSH
- roboticky asistované výkony * metody statistika a číselné údaje MeSH
- statistika jako téma MeSH
- stupeň závažnosti nemoci MeSH
- terapie metody statistika a číselné údaje MeSH
- thymektomie * metody MeSH
- thymom chirurgie diagnostické zobrazování MeSH
- thymus chirurgie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Myasthenia gravis (MG) is a prototypical autoimmune disease of the neuromuscular junction (NMJ). The study of the underlying pathophysiology has provided novel insights into the interplay of autoantibodies and complement-mediated tissue damage. Experimental autoimmune myasthenia gravis (EAMG) emerged as a valuable animal model, designed to gain further insight and to test novel therapeutic approaches for MG. However, the availability of native acetylcholine receptor (AChR) protein is limited favouring the use of recombinant proteins. To provide a simplified platform for the study of MG, we established a model of EAMG using a recombinant protein containing the immunogenic sequence of AChR in mice. This model recapitulates key features of EAMG, including fatigable muscle weakness, the presence of anti-AChR-antibodies, and engagement of the NMJ by complement and a reduced NMJ density. Further characterization of this model demonstrated a prominent B cell immunopathology supported by T follicular helper cells. Taken together, the herein-presented EAMG model may be a valuable tool for the study of MG pathophysiology and the pre-clinical testing of therapeutic applications.
IMPORTANCE: The temporal association between the occurrence of neurological diseases, many autoimmune diseases, and vaccination against SARS-CoV-2 has been topically interesting and remains hotly debated both in the medical literature and the clinic. Given the very low incidences of these events both naturally occurring and in relation to vaccination, it is challenging to determine with certainty whether there is any causative association and most certainly what the pathophysiology of that causation could be. OBSERVATIONS: Data from international cohorts including millions of vaccinated individuals suggest that there is a probable association between the adenovirus-vectored vaccines and Guillain-Barré syndrome (GBS). Further associations between other SARS-CoV-2 vaccines and GBS or Bell palsy have not been clearly demonstrated in large cohort studies, but the possible rare occurrence of Bell palsy following messenger RNA vaccination is a topic of interest. It is also yet to be clearly demonstrated that any other neurological diseases, such as central nervous system demyelinating disease or myasthenia gravis, have any causative association with vaccination against SARS-CoV-2 using any vaccine type, although it is possible that vaccination may rarely trigger a relapse or worsen symptoms or first presentation in already-diagnosed or susceptible individuals. CONCLUSIONS AND RELEVANCE: The associated risk between SARS-CoV-2 vaccination and GBS, and possibly Bell palsy, is slight, and this should not change the recommendation for individuals to be vaccinated. The same advice should be given to those with preexisting neurological autoimmune disease.
- MeSH
- Bellova paréza * MeSH
- COVID-19 * prevence a kontrola MeSH
- Guillainův-Barrého syndrom * etiologie MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- myasthenia gravis * MeSH
- SARS-CoV-2 MeSH
- vakcinace škodlivé účinky MeSH
- vakcíny proti COVID-19 škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
