Characteristics of myasthenia gravis in elderly patients: a retrospective study.

BACKGROUND: The incidence of myasthenia gravis (MG) is increasing, and its characteristics in elderly patients are believed to differ from those in younger patients. However, only a few studies have focused on elderly patients with MG. OBJECTIVE: To review the characteristics of MG in elderly patients and evaluate whether older age is an independent factor associated with achieving minimal manifestation status (MMS). METHODS: This retrospective cohort study included 367 patients (319 non-elderly and 48 elderly patients) with MG enrolled at Xiangya Hospital from September 1, 2016, to December 31, 2018. We collected demographic data and information regarding comorbidities, antibody status, Myasthenia Gravis Foundation of America classification, affected muscle groups, thymoma, and treatment. MMS was defined as the primary outcome. RESULTS: Comorbidities were more common in elderly than in younger patients with MG. Anti-acetylcholine receptor antibody was the dominant subtype, whereas anti-muscle-specific tyrosine kinase antibody was rare and detected only in non-elderly patients. Elderly patients were more likely than younger patients to have generalized MG, but the frequency of thymoma was lower (28.5% vs. 10.4%, p = 0.0078). MMS or better was achieved in 154 (48.3%) and 13 (27.1%) non-elderly and elderly patients, respectively. Older age did not appear to be an independent factor associated with MMS (hazard ratio = 0.625; 95% confidence interval, 0.345-1.131). CONCLUSIONS: Older age was not an independent factor for a worse prognosis in patients with MG. The treatment of elderly patients with MG should be individually tailored.

Tacrolimus as Single-Agent Immunotherapy and Minimal Manifestation Status in Nonthymoma Myasthenia Gravis.

BACKGROUND: Tacrolimus is a second-line immunosuppressant in myasthenia gravis (MG) therapy, which is mainly used in combination with corticosteroids to reduce steroid dose and maintain the effect of immunotherapy. However, few studies have focused on the effect of tacrolimus as single-agent immunotherapy on achieving minimal manifestation status (MMS). Thus, this study is aimed at exploring the efficacy and influencing factors of tacrolimus as single-agent immunotherapy in MG. METHODS: Clinical data of 75 nonthymoma MG patients treated with tacrolimus single-agent as initial immunotherapy were retrospectively analyzed. The therapeutic effect was evaluated by Myasthenia Gravis Foundation of America postintervention status. Clinical factors affecting the achievement of MMS and treatment reactivity of different MG subtypes were determined by Cox regression analysis. RESULTS: Tacrolimus was generally safe, with only two patients (2.7%) switching medications due to side effects. 32% of patients had improved symptoms after 1 month of treatment. 69.2% of patients achieved MMS or better after one year. The age < 39 years old, QMG score < 11 points, and AChR - Ab titer < 8.07 nmol/L were indicative of a favorable response, which was independent of gender, course of the disease. As for MG subtypes, ocular and seronegative MG showed better treatment sensitivity. CONCLUSIONS: Tacrolimus as single-agent immunotherapy takes effect quickly and can effectively enable nonthymoma MG patients to achieve MMS. Tacrolimus can be used alone for the initial immunotherapy of MG patients, especially for young, mild, and low antibody titer patients.

Evaluation of outcome measures for myasthenia gravis subgroups.

INTRODUCTION: Disease evaluation and long-term follow-up of myasthenia gravis (MG) patients rely on disease-specific measures. We evaluated four widely used MG-specific assessments, and compared the response to disease change in different MG subgroups. METHODS: We used the Cronbach's α coefficient to test reliability, Pearson correlation coefficients to test construct validity, as well as one-way ANOVA and independent-sample t-tests to access discriminant validity. Analyses of similar items between QMG and MG-ADL included paired-sample t-tests and mean score comparisons. Pearson correlation coefficients were used to describe the correlation between changes of QMG, MG-ADL, MG-QOL15r and MGC. The Wilcoxon matched-pairs signed-ranks test was performed to compare the outcomes. RESULTS: 872 MG patients were enrolled. QMG, MG-ADL, MG-QOL15r, and MGC all exhibited high reliability. All four scales displayed good discriminant validity according to the MGFA classification and MGC score. MG-ADL showed significant differences between patients grouped by age and gender, and MG-QOL15r showed significant differences between patients grouped by age. Analyses of similar items showed that MG-ADL achieved higher scores in bulbar items, whereas QMG produced higher scores in limb items. For patients in remission or minimal manifestation status, QMG exhibited significantly greater improvement than MG-QOL15r. In patients of MGFA I, II, III, and IV, QMG showed significantly greater improvement than MG-ADL. CONCLUSIONS: Patient-reported scale is an important supplement for a given period. MG-ADL has a better response to severe disease, and MG-QOL15r is more comprehensive for patients in remission or minimal manifestation status.

Prognostic Analysis of Thymoma-Associated Myasthenia Gravis (MG) in Chinese Patients and Its Implication of MG Management: Experiences from a Tertiary Hospital.

BACKGROUND: Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular disorder. Approximately 10-20% of all MG patients experience thymoma (benign tumor arising from thymus tissue). Thymectomy has been the standard of care for thymomatous myasthenia gravis (TMG). However, the clinical outcome of TMG after thymectomy has not been sufficiently studied, especially the long-term prognosis. Therefore, the aim of this study was to analyze the clinical characteristics contributing to the prognostic factors of TMG. METHODS: We reviewed 70 TMG patients in the Xiangya Hospital and classified them into the minimal manifestation (MM) group and No MM group, according to the long-term treatment outcome. MM-or-better status was defined as the goal treatment for TMG patients. We collected and analyzed the demographic data, the WHO classification of thymoma, MG-associated antibody levels, disease severity, treatment-related data as well as clinical outcome at six months. Variables selected by univariate analysis were used in the multivariate logistic regression model to identify the prognostic factors. RESULTS: The differences in clinical outcome at six months and worst QMGS were significant, while the differences in other factors were insignificant between groups. Clinical outcome at six months (OR=23.5 95% CI 2.4-231.5, P=0.007) and dyspnea before thymectomy (OR=0.2, 95% CI 0.03-0.75, P=0.021) were identified as the prognostic factors of long-term treatment. CONCLUSION: Demographic and clinical features were similar in TMG patients treated at our hospital. The early achievement of MM-or-better status may indicate a good outcome in the long term. Dyspnea before thymectomy appears to associate with a poor prognosis.

Multiple genetic factors affecting the pharmacokinetic and pharmacodynamic processes of tacrolimus in Chinese myasthenia gravis patients.

PURPOSE: Tacrolimus is a novel effective immunosuppressant for myasthenia gravis (MG) patients. However, the narrow therapeutic window, and high inter- and intrapatient variation in bioavailability largely limited its clinical application. This article intended to find the SNPs influencing clinical outcome and discover the possible mechanisms. METHODS: Based on the tagSNPs genotyped by Improved Multiple Ligase Detection Reaction, Plink 1.07 was used to find the SNPs having close interaction to tacrolimus serum concentration, QMG score changes or even reasonable drug dose. Then we searched several databases to predict the possible miRNA binding rs15524 sequence. Based on the prediction, dual-luciferase reporter assay and miRNA transfection were used to discover the mechanism of how SNP rs15524 controls tacrolimus serum concentration through influencing CYP3A5 expression. RESULTS: In this article, we found multiple SNPs on CYP3A4, CYP3A5, FKBP1A, NFATC2 genes were predicted closely related to tacrolimus serum concentration, therapeutic effect which reflected by QMG score changes or even reasonable drug dose. After in silico miRNA selection, possible relationship between hsa-miR-500a and rs15524 was found. With the help of dual-luciferase reporter assay, wild-type rs15524 (T allele) was found having a stronger binding affinity for hsa-miR-500a. Higher expression of CYP3A5 may also led by lower hsa-miR-500a level. CONCLUSIONS: SNP rs15524 may control CYP3A5 expression by affecting the binding affinity between CYP3A5 3'UTR and hsa-miR-500a. Wild type (T allele) 3'UTR of CYP3A5 has stronger binding affinity to hsa-miR-500a and cause lower CYP3A5 expression and higher tacrolimus serum concentration.