Myasthenia gravis and azathioprine treatment: Adverse events related to thiopurine S-methyl-transferase (TPMT) polymorphisms

2020 ◽  
Vol 412 ◽  
pp. 116734 ◽  
Author(s):  
Paulo José Lorenzoni ◽  
Cláudia Suemi Kamoi Kay ◽  
Marcelo Farago Zanlorenzi ◽  
Renata Dal-Prá Ducci ◽  
Lineu Cesar Werneck ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myasthenia Gravis ◽  
Methyl Transferase ◽  
Azathioprine Treatment

scholarly journals Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis

Neurology ◽  
2019 ◽  
Vol 92 (23) ◽  
pp. e2661-e2673 ◽  
Author(s):  
James F. Howard ◽  
Vera Bril ◽  
Ted M. Burns ◽  
Renato Mantegazza ◽  
Malgorzata Bilinska ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myasthenia Gravis ◽  
Vital Signs ◽  
Standard Of Care ◽  
Placebo Treatment ◽  
Phase 2 ◽  
Double Blind ◽  
Severity Scores ◽  
Quality Of Life Scale ◽  
Life Scale

ObjectiveTo investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment.MethodsA phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity.ResultsOf the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement.ConclusionsEfgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG.Classification of evidenceThis study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.

Myasthenia Gravis Associated With Programmed Death-1 (PD-1) Receptor Inhibitor Pembrolizumab: A 40-day Case Report

2020 ◽  
pp. 089719002097075
Author(s):  
Aidan S. Ziobro ◽  
Reid L. LaPlante ◽  
Shayna R. DeMari ◽  
Larissa M. Clark ◽  
David J. Kingsley ◽  
...  
Keyword(s):  
Cell Death ◽  
Case Report ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Myasthenia Gravis ◽  
Cardiopulmonary Arrest ◽  
Palliative Therapy ◽  
Treatment Modalities ◽  
Duration Of Treatment ◽  
Serious Adverse Events

Purpose: This case report describes myasthenia gravis-like symptoms after treatment with a programmed cell death 1 inhibitor, pembrolizumab, the treatment modalities utilized, and associated patient outcomes. Summary: A 76-year old male treated with pembrolizumab for palliative therapy for metastatic melanoma presented with increasing weakness, neck pain, diplopia in the left eye, abducens palsy, periorbital edema, and decreased appetite. The patient was diagnosed with acetylcholine receptor antibody (AChR) negative myasthenia gravis. The patient was started on prednisone 1 mg/kg/day, followed by pyridostigmine 60 mg by mouth 3 times a day, and IVIg for 5 days. Due to minor improvements in myasthenia gravis symptoms, 5 cycles of plasmapheresis were ordered. The patient was successfully treated for aspiration pneumonia after cardiopulmonary arrest. On day 28, the patient was diagnosed with ventilator associated pneumonia and received appropriate therapy. Due to ICU agitation and delirium, VAP, and long duration of treatment, the patient requested withdrawal of care and passed. Conclusion: Programmed cell death inhibitors, such as pembrolizumab, can provide great benefit to patients but can also be associated with rare but serious adverse events. With new reports of MG after use, providers should continually weigh the benefits versus harm in using these products and monitor patients closely for such adverse events.

Alternative to steroid therapy for myasthenia gravis and myositis occurring as immune‐related adverse events

2019 ◽  
Vol 10 (3) ◽  
pp. 190-191 ◽  
Author(s):  
Sachiko Kamada ◽  
Akira Hanazono ◽  
Yui Sanpei ◽  
Takamitsu Inoue ◽  
Shigeaki Suzuki ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myasthenia Gravis ◽  
Steroid Therapy

scholarly journals Efficacy and Safety of the TCM Qi-Supplementing Therapy in Patients with Myasthenia Gravis: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xi-qian Yang ◽  
Ling Liu ◽  
Wen-yu Yang ◽  
Huan-huan Dong ◽  
Yi-ran Yang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myasthenia Gravis ◽  
Relapse Rate ◽  
Response Rate ◽  
Meta Analysis ◽  
Effective Rate ◽  
Efficacy And Safety ◽  
Total Response ◽  
Total Response Rate

Background. The Traditional Chinese Medicine (TCM) Qi-supplementing therapy has been used widely for treating myasthenia gravis (MG) in China. The purpose of this meta-analysis was to evaluate the efficacy and safety of Qi-supplementing therapy as an adjunctive therapy in MG patients. Methods. Seven electronic databases were searched through June 2016. Randomized controlled trials (RCTs) evaluating the add-on effect of Qi-supplementing therapy in MG patients were included. The outcome measures were the total effective rate, relapse rate, and adverse events. Results. Twenty-three RCTs involving 1,691 MG patients were included. The included studies were of low-to-moderate quality. Meta-analysis showed that Qi-supplementing therapy combined with Western medicine (WM) significantly improved the total response rate and reduced the relapse risk during 6–24 months of follow-up. Subgroup analysis showed that Qi-supplementing therapy only affected the total response rate within the first 6 months of treatment. Moreover, the rate of adverse events was lower with the addition of Qi-supplementing therapy to WM than with WM only. Conclusions. Short-term Qi-supplementing therapy combined with WM appears to be superior to WM for improving the total response rate and reducing the relapse rate. However, more high-quality RCTs are warranted owing to methodological flaws of previous trials.

Predictors of steroid-refractory immune checkpoint inhibitor associated myocarditis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Power ◽  
W Meijers ◽  
C Fenioux ◽  
Y Tamura ◽  
A Asnani ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Adverse Events ◽  
Myasthenia Gravis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Funding Source ◽  
Daily Dose ◽  
Age And Sex ◽  
Steroid Refractory

Abstract Background/Introduction Immune checkpoint inhibitor (ICI)-associated myocarditis has a high mortality rate of approximately 50%. Clinical decompensation often occurs despite first-line treatment with corticosteroids. Factors associated with steroid failure are currently unknown. Purpose To identify predictors of steroid failure in patients with ICI-associated myocarditis. Methods We developed a web-based registry to collect and study 157 cases with clinical manifestations of ICI-associated myocarditis across 16 countries. Steroid failure was defined as patients who were escalated to immunomodulators after ≥1mg/kg daily dose of prednisone or had in-hospital death due to myocarditis despite ≥1mg/kg daily dose of prednisone. Steroid response was defined as all other patients treated with steroids without escalation to immunomodulators and without death due to myocarditis. A multivariate logistic model accounting for age and sex was used to predict association with steroid failure. Results Compared to steroid responsive cases, steroid failure was more likely to result in fulminant myocarditis (56.7% vs 19.6%, OR=5.37 [2.62–10.98] p<0.001) and all-cause in-hospital mortality (49.1% vs 12.9%, OR=6.50 [2.86–14.73] p<0.001) with shorter time from presentation to death (27.5 vs 43.0 days HR: 2.56 [1.45–4.50] p=0.001). When adjusting for age and sex, cases were more likely to be steroid-refractory if they were female (46.7% vs 30.1%, OR=2.77 [1.31–5.85] p=0.007), higher body mass index (27.2 vs 22.0, OR=1.09 [1.01–1.18] p=0.012), had higher intake creatine kinase (2800.5 vs 528.0 U/L, OR=1.48 [1.14–1.90] p=0.003) had higher intake troponin T (1.40 vs 0.25 ng/mL OR=1.63 [1.00–2.64] p=0.049), or had one or more concomitant non-cardiac immune-related adverse event (90.0% vs 74.2%, OR=3.10 [1.14–8.25] p<0.026). The only immune-related adverse events independently associated with steroid failure in myocarditis were myasthenia gravis-like syndrome (26.7% vs 8.2%, OR=3.84 [1.47–10.10] p=0.006) and myositis (45.0% vs 24.7%, OR=2.38 [1.16–4.92] p=0.018). Steroid failure was not significantly associated with cardiovascular or autoimmune history but was associated with a history of thymoma (12.0% vs 2.6%, OR=18.86 [0.10–356.7] p=0.05) Conclusion(s) Features such as female sex, high body mass index, and pre-existing thymoma as well as findings of elevated cardiac biomarkers and other non-cardiac immune-related adverse events – particularly myositis and myasthenia gravis-like syndrome – may represent a steroid-refractory phenotype of ICI-associated myocarditis. These results suggest that a multidisciplinary approach to diagnosing concomitant non-cardiac immune related adverse events is key to risk-stratifying ICI-associated myocarditis. Forrest Plot Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): National Institutes of Health

scholarly journals Amifampridine phosphate in the treatment of muscle-specific kinase myasthenia gravis: a phase IIb, randomized, double-blind, placebo-controlled, double crossover study

2018 ◽  
Vol 6 ◽  
pp. 205031211881901 ◽  
Author(s):  
Silvia Bonanno ◽  
Maria Barbara Pasanisi ◽  
Rita Frangiamore ◽  
Lorenzo Maggi ◽  
Carlo Antozzi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myasthenia Gravis ◽  
Double Blind ◽  
Quality Of Life Scale ◽  
Life Scale ◽  
Profile Score ◽  
Fatigue Severity ◽  
Muscle Specific Kinase ◽  
To Receive

Objective: The aim of this study is to determine the safety and the efficacy of amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study. Methods: Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–amifampridine–placebo sequence or amifampridine–placebo–amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Quantitative Myasthenia Gravis score and Myasthenia Gravis–specific Activities of Daily Living Profile score. The secondary outcome measures comprised changes from baseline of Myasthenia Gravis Composite score, Myasthenia Gravis Quality of Life scale—15 questions, Fatigue Severity Scale, and Carlo Besta Neurological Institute–Myasthenia Gravis scale. Statistical analyses were assessed using a switchback model for three-period, two-treatment crossover design. Results: A total of 10 patients were screened, enrolled, and treated. Transient paresthesias (60%) were the only amifampridine phosphate–related adverse events reported. Four patients were randomized to receive placebo–amifampridine–placebo sequence and three patients to receive amifampridine–placebo–amifampridine sequence. The co-primary objectives were statistically met (Quantitative Myasthenia Gravis score: p = 0.0003 and Myasthenia Gravis–specific Activities of Daily Living Profile score: p = 0.0006), as well as all the secondary endpoints (Myasthenia Gravis Composite score: p < 0.0001, Myasthenia Gravis Quality of Life scale—15 questions: p = 0.0025, Fatigue Severity Scale: p = 0.0061, and Carlo Besta Neurological Institute–Myasthenia Gravis scale: p = 0.0014). Conclusion: Despite the low number of patients, MuSK-001 study provided evidence that amifampridine phosphate, in the range of 30–60 mg daily dose, was safe and effective in treating muscle-specific kinase myasthenia gravis, suggesting the need for a large multi-center trial to confirm these results.

Cancer occurrence following azathioprine treatment in myasthenia gravis patients: A systematic review and meta-analysis

2021 ◽  
Vol 88 ◽  
pp. 70-74
Author(s):  
Zheyu Zhang ◽  
Meiping Wang ◽  
Liang'e Xu ◽  
Bingze Jiang ◽  
Tianyu Jin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Myasthenia Gravis ◽  
Meta Analysis ◽  
Cancer Occurrence ◽  
Azathioprine Treatment

scholarly journals Treatment of Myasthenia Gravis in Patients with Elderly Onset at Advanced Age

2015 ◽  
Vol 6 ◽  
pp. JCM.S29601 ◽  
Author(s):  
Noriko Nishikawa ◽  
Masahiro Nagai ◽  
Tomoaki Tsujii ◽  
Win T. Kyaw ◽  
Nachi Tanabe ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myasthenia Gravis ◽  
Low Dose ◽  
Late Onset ◽  
Immunosuppressive Treatment ◽  
Advanced Age ◽  
Number Of Patients ◽  
Elderly Onset ◽  
Receptor Antibodies ◽  
Anti Acetylcholine

The number of patients with late-onset myasthenia gravis (MG) among patients ≥50 years has been increasing recently. We encountered three patients who developed elderly-onset MG at a particularly advanced age (≥80 years). All were female and positive for anti-acetylcholine receptor antibodies. About 4 years have passed since MG onset in all three patients and symptoms have been controlled without recurrence using a combination of oral low-dose prednisolone and tacrolimus. As many cases of elderly-onset MG do not require strong immunosuppression, we recommend minimum immunosuppressive treatment to avoid adverse events, particularly in patients at an advanced age of ≥80 years.

scholarly journals Immune Myocarditis Overlapping With Myasthenia Gravis Due to Anti-PD-1 Treatment for a Chordoma Patient: A Case Report and Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Shujing Liang ◽  
Jingxian Yang ◽  
Yun Lin ◽  
Tong Li ◽  
Wenrong Zhao ◽  
...  
Keyword(s):  
Case Report ◽  
Survival Rate ◽  
Side Effects ◽  
Literature Review ◽  
Best Practices ◽  
Adverse Events ◽  
Myasthenia Gravis ◽  
Effective Treatment ◽  
Malignant Tumor ◽  
Clinical Benefit

Immunotherapy begins to be widely used due to the increasing exploration and gratifying effects in multiple cancers. Chordoma, as a rare bone malignant tumor, often recurs and metastasizes after undergoing surgery and radiotherapy. Therefore, immunotherapy can be explored as an emerging, potentially effective treatment to improve the survival rate and clinical benefit of patients. However, a variety of immune-related adverse events (irAEs) cannot be avoided completely. And the immunotherapy-induced myocarditis, as a rare but fatal irAE, has been increasingly reported. Understanding the mechanism involved in irAEs can inform best practices for side effects management. Here, we firstly reported a case of immune myocarditis and subsequent myasthenia gravis (MG) following anti-PD-1 treatment for chordoma.

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