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Frontiers in Neurology 2024
PubMed: 38919972
DOI: 10.3389/fneur.2024.1418631 -
Frontiers in Neurology 2024To describe the early experience of ravulizumab use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG).
PURPOSE
To describe the early experience of ravulizumab use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG).
METHODS
This multicenter retrospective study included AChR+ve gMG patients who were treated with ravulizumab and had both pre- and post-ravulizumab myasthenia gravis activities of daily living (MG-ADL) scores. Clinical information regarding MG history, concomitant treatment(s), MG-ADL, other MG-specific measures, and adverse events were recorded.
RESULTS
A total of 18 patients with mean age of 61.83 (±16.08, = 18) years were included in this cohort. In 10 complement inhibitor naive patients, a clinically meaningful reduction in mean Mg-ADL (baseline: 6.6 (±3.58) vs. 4.4 (±2.28), post ravulizumab) was seen. 6 out of 10 patients (60%) had clinically meaningful reduction post ravulizumab and two achieved minimum symptom expression (MSE). In 8 patients switched from eculizumab to ravulizumab, further reduction was noted in post ravulizumab mean MG-ADL (Baseline: 3.25 (±3.34) vs. 1.5 (±2.34) post ravulizumab). None of the patients who switched from eculizumab to ravulizumab experienced worsening symptoms. Eleven out of 14 (78.5%) patients on prednisone therapy were able to reduce their prednisone dose post-ravulizumab. None of the patients experienced any major side effects.
CONCLUSION
In our clinical practice, 60% of AChR+ve gMG complement inhibitor naive patients experienced a clinically meaningful improvement in MG-ADL scores with ravulizumab. Patients were safely switched from eculizumab to ravulizumab and had further improvement in their mean MG-ADL scores. Of those on prednisone therapy, the majority were able to reduce their prednisone dosage.
PubMed: 38919970
DOI: 10.3389/fneur.2024.1378080 -
Neurology. Clinical Practice Oct 2024In 2016, a randomized controlled trial demonstrated the clinical efficacy of trans-sternal thymectomy for patients with non-thymomatous myasthenia gravis (MG). Whether...
BACKGROUND AND OBJECTIVES
In 2016, a randomized controlled trial demonstrated the clinical efficacy of trans-sternal thymectomy for patients with non-thymomatous myasthenia gravis (MG). Whether large-scale changes occurred in clinical practice after this trial is unknown.
METHODS
We performed a retrospective longitudinal cross-sectional analysis using National Inpatient Sample (NIS) data from 2012 to 2019. Our study included hospitalized adults at least 18 years of age diagnosed with MG without an associated thymoma. We used joinpoint regression to analyze annual trends in thymectomy volume and surgical approach (minimally invasive vs trans-sternal) from 2012 to 2019. Using logistic regression models, we examined patient and hospital-level factors that may have influenced whether thymectomy was performed, such as age, sex, race, insurance payor, hospital size and teaching status, and Elixhauser Comorbidity Index. Sampling weights were applied to account for the complex survey design of NIS.
RESULTS
The total number of thymectomy procedures increased by 69.8% per year (95% CI 40.1-105.8) between 2012 and 2019. Trans-sternal thymectomies increased by 62.8% per year (95% CI 35.8-95.2) and minimally invasive thymectomies by 83.7% per year (95% CI 38.1-144.3). Thymectomies were significantly more likely to occur in 2017-2019 compared with 2012-2016 (OR 1.93, 95% CI 1.62-2.31). In a multivariable regression model, several factors decreased the odds of patients with MG having a thymectomy: older age, Black race (OR 0.62, 95% CI 0.49-0.77), female (OR 0.73, 95% CI 0.63-0.86), and higher Elixhauser Comorbidity Index. Patients in medium (OR 1.82, 95% CI 1.30-2.55) or large (OR 2.81, 95% CI 2.07-3.82) size and urban teaching hospitals (OR 6.09, 95% CI 2.65-13.97) were more likely to undergo thymectomy.
DISCUSSION
Thymectomy is being performed more frequently for non-thymomatous MG, especially after 2016 after publication of a positive phase III clinical trial. There are several disparities in thymectomy utilization that warrant further attention.
PubMed: 38919930
DOI: 10.1212/CPJ.0000000000200335 -
Neurology and Therapy Jun 2024
PubMed: 38916784
DOI: 10.1007/s40120-024-00639-0 -
Updates in Surgery Jun 2024The recommended treatment for early stage thymoma without myasthenia gravis is complete thymectomy (CT). Limited thymectomy (LT) (simply resecting the thymoma with safe...
The recommended treatment for early stage thymoma without myasthenia gravis is complete thymectomy (CT). Limited thymectomy (LT) (simply resecting the thymoma with safe surgical margins) is gaining popularity. In this study, we compared the surgical and oncological results of complete and limited thymectomy in non-myasthenic patients with early stage thymoma. Non-myasthenic, Masaoka stage I-II, 86 patients who underwent surgical resection for thymoma were included in the study. Complete thymectomy (n:44) included patients who had resection of the thymoma together with the entire thymus and limited thymectomy (n:42) included patients who had resection of the thymoma without remaining thymus. The surgical approach, tumor size, histological type, pathological stage, adjuvant therapy, complications, postop myasthenia gravis, recurrence and death were recorded and compared between groups. Complete thymectomy group had more WHO type B1-3 tumors, more complications and more deaths than patients in the limited thymectomy group (p = 0.03, 0.018 and 0.023 respectively). Although statistically not significant CT group had more recurrences than LT group (11.4%/4.8%, p = 0.43). The 10-year freedom from recurrence (FFR) rate in the CT group was 84.8% and in the LT group ıt was 97.6%, the difference was not statistically significant (p = 0.15). None of the factors including surgical extent analysed with univariate and multivariate analysis had a significant effect on FFR. Limited thymectomy may be a good treatment option for non-myasthenic early stage thymoma patients but randomized controlled trials with long follow-up periods, ideally comparing patients operated with minimally invasive surgery are necessary.
PubMed: 38913297
DOI: 10.1007/s13304-024-01918-z -
Surgery Today Jun 2024To evaluate the usefulness of robotic subxiphoid-optical thymectomy (RST).
PURPOSE
To evaluate the usefulness of robotic subxiphoid-optical thymectomy (RST).
METHODS
Thirty-seven procedures (thymoma, n = 19; thymic carcinoma, n = 1; myasthenia gravis, n = 3; and others, n = 14) performed between October 2020 and December 2023 were included. The right and left 6th intercostal midclavicular lines and subxiphoid, with an assistant port placed in the right third intercostal anterior axillary line, were adapted. Postoperative pain was assessed using a numerical rating scale (NRS).
RESULTS
A good view of the surgical field is obtained. The median console time was 113 min and the time to roll-in was 30 min. The body mass index (BMI) was 21.6. One patient with thymic carcinoma required combined resection of the left phrenic nerve and left brachiocephalic vein without conversion to thoracotomy, and 1 patient had post-pericardiotomy syndrome with bilateral pleural effusion. There was a correlation between the prolonged time to roll-in and BMI (ρ = 0.439; p = 0.007). Pain was controlled with oral medication on postoperative day 1 and significantly decreased at discharge and at the first outpatient visit without epidural anesthesia (median NRS scores: 4, 1, and 1, respectively).
CONCLUSION
RST is a safe procedure that provides surgeons with a sufficient view of the anterior mediastinum and causes minimal postoperative pain.
PubMed: 38913156
DOI: 10.1007/s00595-024-02887-x -
Frontiers in Immunology 2024Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who...
Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who experience acute exacerbations and do not respond to conventional treatments, there is an urgent need to find more suitable treatment options. With the advent of biologic agents, efgartigimod has shown promising results in the treatment of MG. We report a 65-year-old MuSK-MG patient who presented with impaired eye movements initially, and the symptoms rapidly worsened within a week, affecting the limbs and neck muscles, and had difficulties in chewing and swallowing. Lymphoplasmapheresis did not achieve satisfactory results, but after a cycle of efgartigimod treatment, the patient's symptoms gradually improved and remained in a good clinical state for several months.
Topics: Humans; Myasthenia Gravis; Aged; Receptors, Cholinergic; Treatment Outcome; Receptor Protein-Tyrosine Kinases; Autoantibodies; Male; Female
PubMed: 38911858
DOI: 10.3389/fimmu.2024.1401972 -
Die Ophthalmologie Jun 2024Myasthenia gravis is a well-understood autoimmune disease of the neuromuscular synapse that is medicinally treatable with favorable results and therefore should not be... (Review)
Review
Myasthenia gravis is a well-understood autoimmune disease of the neuromuscular synapse that is medicinally treatable with favorable results and therefore should not be overlooked in the differential diagnostic evaluation of vertical diplopia. Myasthenia is primarily a clinical diagnosis. Positive indications include double vision of fluctuating severity, diurnal variations, double vision after lengthy gaze fixation on a distant object and in the primary position as well as diplopia in various visual directions, often associated with a varying extent of ptosis. Clinical tests are the Simpson test, the ice on eyes test and the probatory administration of pyridostigmine. Positive results corroborate this diagnosis but negative results do not exclude myasthenia. The same applies for the determination of specific autoantibodies. In addition to ocular symptoms it is important to search for generalized symptoms and bulbopharyngeal symptoms in particular should prompt immediate neurological diagnostics. In addition to symptomatic treatment a wide range of immunotherapeutic agents are available. Thymectomy is also used for immunomodulatory indications according to the 2023 revised guidelines. Patient-centered treatment goals, patient education and comprehensive information, also via the self-help organization German Myasthenia Society, are essential components of successful treatment of myasthenia.
PubMed: 38904720
DOI: 10.1007/s00347-024-02061-1 -
Frontiers in Immunology 2024Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating... (Review)
Review
Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Current treatment of MG based on international consensus guidelines allows to effectively control symptoms, but most patients do not reach complete stable remission and require life-long immunosuppressive (IS) therapies. Moreover, a proportion of them is refractory to conventional IS treatment, highlighting the need for more specific and tailored strategies. Precision medicine is a new frontier of medicine that promises to greatly increase therapeutic success in several diseases, including autoimmune conditions. In MG, B cell activation, antibody recycling and NMJ damage by the complement system are crucial mechanisms, and their targeting by innovative biological drugs has been proven to be effective and safe in clinical trials. The switch from conventional IS to novel precision medicine approaches based on these drugs could prospectively and significantly improve MG care. In this review, we provide an overview of key immunopathogenetic processes underlying MG, and discuss on emerging biological drugs targeting them. We also discuss on future direction of research to address the need for patients' stratification in endotypes according with genetic and molecular biomarkers for successful clinical decision making within precision medicine workflow.
Topics: Humans; Myasthenia Gravis; Precision Medicine; Autoantibodies; Autoimmunity; Animals; Immunosuppressive Agents; Neuromuscular Junction
PubMed: 38903526
DOI: 10.3389/fimmu.2024.1404191 -
Muscle & Nerve Jun 2024Efgartigimod, a neonatal Fc-receptor inhibitor, has recently been approved as treatment for myasthenia gravis (MG). In this retrospective cohort study, we aimed to...
INTRODUCTION/AIMS
Efgartigimod, a neonatal Fc-receptor inhibitor, has recently been approved as treatment for myasthenia gravis (MG). In this retrospective cohort study, we aimed to systematically assess short- and long-term effectiveness of efgartigimod in patients with refractory MG.
METHODS
Sixteen patients with refractory autoimmune acetylcholine receptor MG were treated with efgartigimod. Data were collected from January 2021 to March 2023 on Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis score (QMG), Myasthenia Gravis Composite score (MGC) and the 15-item revised version of the Myasthenia Gravis Quality of Life questionnaire (MG-QoL15r).
RESULTS
A favorable outcome was seen in 56% of patients at the last measurement. Out of 16 patients, 50% were an MG-ADL responder after the first treatment cycle. After 4 weeks, a clinically meaningful improvement compared to baseline was seen on the MG-ADL, QMG, and MGC. There was a statistically significant improvement on the MGQoL15r from baseline to week 4. The improvement was maintained until the last measurement for the MGC and the MGQoL15r. At the last visit, all patients had discontinued 4-weekly dosages, shifting to administration frequencies of 1, 2, or 3 weeks. Drug doses could be decreased for prednisolone (n = 7), azathioprine (n = 2), and intravenous immunoglobulin (n = 9). Frequency of plasma exchange was decreased in nine patients.
DISCUSSION
In patients with refractory MG, efgartigimod was effective for at least half of all patients. Patients required more frequent dosing compared to the ADAPT phase 3 trial. In 80% of the patients concurrent medication could be reduced or discontinued.
PubMed: 38899431
DOI: 10.1002/mus.28184