•Compare the difference of clinical data between mild MG, severe MG, and HC.•NLR > 2.37 can differentiate severe MG from mild MG.•NLR may be a helpful marker to evaluate the severity disease of ...patients with MG especially mild MG.
The study aimed to explore the clinical value of neutrophil-to-lymphocyte (NLR) in evaluating myasthenia gravis (MG) severity and the correlation between NLR and the Quantitative Myasthenia Gravis Score (QMGS).
This study included 128 patients with MG and 116 healthy controls. We completed Myasthenia Gravis Foundation of America (MGFA) classification for patients with MG, and defined MGFA I, II, and III as mild MG and MGFA IV and V as severe MG. The NLR of the patients were calculated, and statistical analysis was performed, with statistical significance set at P < 0.05. When pairwise comparisons between patients with mild MG, severe MG, and the healthy controls were performed, P < 0.017 was considered statistically significant under Bonferroni correction.
NLR was significantly higher in patients with severe MG than in those with mild MG 2.90(2.41–5.83) vs 1.72(1.38–2.51), P = 0.000 and in the healthy controls 2.90(2.41–5.83) vs 1.65(1.34–1.91), P = 0.000. NLR was independently associated with severe MG. The cut-off value of NLR for differentiating mild MG from severe MG was 2.37, and the sensitivity and specificity were 0.900 and 0.815, respectively. The results of Spearman test showed that NLR was positively correlated with QMGS in mild MG. NLR tended to be correlated QMGS in patients with severe MG, but the difference was not statistically significant.
NLR may be a helpful marker for identifying patients with severe MG. NLR can also be used to further evaluate disease severity, especially for mild MG.
Within the last 5 years, the US Food and Drug Administration (FDA) has approved complement and neonatal Fc receptor (FcRN) inhibitors for treatment of generalized myasthenia gravis, and several other ...therapies are in late‐stage clinical trials or under regulatory review. However, questions about which patients are most likely to benefit from which therapies, and the relative effectiveness of these very expensive drugs, has resulted in uncertainty around the place that they should occupy in the existing therapeutic armamentarium. MGNet (a Rare Diseases Clinical Research Consortium funded by the National Institute of Neurological Diseases and Stroke) held two meetings during the 14th International Conference of the Myasthenia Gravis Foundation of America to discuss the most critical needs for clinical trial readiness and biomarker development in the context of therapy development for myasthenia gravis. Herein we provide a summary of these discussions, but not a consensus opinion, and offer a series of recommendations to guide focused research in the most critical areas. We welcome ongoing discussion through comments on this work.
Background and purpose
Data on maintenance therapy with subcutaneous immunoglobulin (SCIg) in myasthenia gravis (MG) are limited. We report on transitioning acetylcholine receptor (AChR) ...antibody‐positive (Ab+) MG patients on stable intravenous immunoglobulin (IVIg) regimens as part of routine clinical care to SCIg 1:1.2.
Methods
This multicenter North American open‐label prospective investigator‐initiated study had two components: the IVIg Stabilization Period (ISP) enrolling patients already on IVIg as part of routine clinical care (Weeks −10 to −1), followed by transition of stable MG subjects to SCIg in the Experimental Treatment Period (ETP; Weeks 0 to 12). We hypothesized that >65% of patients entering the ETP would have a stable Quantitative Myasthenia Gravis (QMG) score from Week 0 to Week 12. Secondary outcome measures included other efficacy measures, safety, tolerability, IgG levels, and treatment satisfaction.
Results
We recruited 23 patients in the ISP, and 22 entered the ETP. A total of 12 subjects (54.5%) were female, and 18 (81.8%) were White, with mean age 51.4 ± 17 years. We obtained Week 12 ETP QMG data on 19 of 22; one subject withdrew from ETP owing to clinical deterioration, and two subjects withdrew due to dislike of needles. On primary analysis, 19 of 22 participants (86.4%, 95% confidence interval = 0.72–1.00) were treatment successes using last observation carried forward (p = 0.018). Secondary efficacy measures supported MG stability. SCIg was safe and well tolerated, and IgG levels were stable. Treatment satisfaction was comparable between ISP and ETP.
Conclusions
MG patients on IVIg as part of their routine clinical care remained stable on monthly IVIg dosage, and most maintained similar disease stability on SCIg.
Background
The subxiphoid approach has been widely used recently. However, there is little data focusing on neurological outcomes in patients with thymomatous myasthenia gravis (MG) who underwent ...subxiphoid thoracoscopic thymectomy. The purpose of this study was to compare the neurological outcomes of patients with thymomatous MG who underwent extended thymectomy with a subxiphoid or transthoracic approach 1 year postoperatively.
Methods
The records of patients with Masaoka stage I and II thymomas who underwent extended thymectomy from January 2019 to December 2020 with tumor size less than 5 cm and thymomatous MG were retrospectively reviewed and evaluated. Neurological outcomes were measured by a quantitative myasthenia gravis score (QMGS), with a 2.3-point reduction in QMGS associated with improvement in clinical MG status. The clinical efficacy and variables affecting the outcomes were assessed using the Kaplan–Meier method and Cox proportional hazard regression analysis.
Results
A total of 89 patients were included in the analysis, of which 44 had a subxiphoid approach and 45 had a trans-sternal approach. Mean QMGS decreased from 12 at initial diagnosis to 8.7 preoperatively and 5.6 at 12 months postoperatively in the subxiphoid group and from 12.1 to 8.9 to 6.0 in the transthoracic group. Thirteen patients (28.9%) who underwent the trans-sternal approach and 10 (22.7%) who underwent the subxiphoid approach did not have an improved clinical status compared with their preoperative status. The median time to clinical improvement was 3 months (95% CI, 2.15–3.85) for the subxiphoid approach and 6 months (95% CI, 5.54–6.46) for the trans-sternal approach. Univariate results showed that the subxiphoid approach was associated with a faster improvement in clinical status (HR = 1.701, 95% CI, 1.044–2.773,
P
< 0.05), and age ≦48 was associated with a faster improvement in clinical status (HR = 1.709, 95% CI, 1.044–2.799,
P
< 0.05). The multivariate model including age ≦48 (HR = 1.837, 95% CI, 1.093–3.086,
P
= 0.022) and the subxiphoid approach (HR = 1.892, 95% CI, 1.127–3.177,
P
= 0.016) was significantly associated with a faster improvement in clinical status.
Conclusions
In patients with Masaoka stage I and II thymoma who underwent thymectomy, with tumor size less than 5 cm and thymomatous MG, age ≦48 years and the subxiphoid approach were associated with a rapid improvement in clinical status.
The quantitative myasthenia gravis score is a commonly used scale for evaluating muscle weakness associated with myasthenia gravis (MG). It has been reported that some items used in the scale have ...low discriminative properties. However, there has been no research investigating the applicability of the quantitative MG score (QMGS) in Chinese patients with MG. In addition, the scoring method and ranges of grip strength items in QMGS need to be further evaluated.
This study included 106 Chinese patients with MG, enrolled between September 2020 and February 2021, who were evaluated using the QMGS. Each item in the QMGS was analyzed for distribution. Three methods of evaluating grip strength, grip strength decrement, maximum grip strength, and relative grip strength, were compared. The correlation between the QMG total score minus grip strength score, and three evaluating methods, was analyzed.
The grip strength, swallowing, speech, diplopia, ptosis, and facial muscles items showed a clustered distribution. Most patients (94%) presented their maximum grip strength in the first four grip strength measurements. The QMG total score minus the grip strength score had a weak correlation with grip strength decrement (R grip
= 0.276; L grip
= 0.353, both
< 0.05) and moderate correlations with maximum grip strength (R grip
= -0.508; L grip
= -0.507; both
< 0.001) and relative grip strength (R grip
= -0.494; L grip
= -0.497, both
< 0.001).
This study suggested that partial items in the QMGS have low discriminative properties for Chinese populations and the maximum grip strength value is the better method to evaluate grip strength compared to the other two scoring methods. Based on the quartiles of maximum grip strength, we propose new scoring ranges for the grip strength items.
This study aimed to quantitatively evaluate placebo effect and drug efficacy characteristics and identify associated factors that affect quantitative myasthenia gravis (MG) score (QMGs) and MG ...activities of daily living score (MG-ADLs) in patients with MG.
Randomized placebo-controlled clinical trials were comprehensively searched in public databases (PubMed, EMBASE, and Cochrane Library databases).
A model-based meta-analysis was developed to describe time-course about drug efficacy and placebo effect.
Twelve articles including 13 trials (673 participants) that were eligible for this study evaluated four immunosuppressants (tacrolimus, cyclosporine, prednisone, and mycophenolate mofetil) and five targeted therapy drugs (eculizumab, belimumab, zilucoplan, efgartigimod, and iscalimab). The pharmacodynamic model showed that eculizumab had the highest efficacy in reducing QMGs scores (3.66 points), and efgartigimod had the highest efficacy in reducing MG-ADLs scores (1.97 points). The placebo effect of QMGs and MG-ADLs increased apparently with time and reached 52% and 90% of their maximum effect in 12 weeks, respectively. In addition, this study found that the activities of daily living ability increased with the increase of the proportion of patients undergoing thymectomy.
This study analyzed the efficacy characteristics of nine drugs. The present findings provide necessary quantitative information for drug development of MG.
Minimal manifestation (MM) or better was recommended as the treatment goal for myasthenia gravis (MG). The sustainability of this status has not been described quantitatively in patients who had ...attained or are close to it.
Patients who were with no or slight impact on daily living were recruited and followed at baseline and 3, 6, and 12 months. The included patients were classified into 3 post-intervention status (PIS) categories: remission (R), MM, and slight impact (SI). The proportion of patients belonging to real-time (not considering the intervals between assessments) and sustained (considering the intervals between assessments) PIS categories was compared at each follow-up. A sensitivity analysis (SA) cohort was established by including patients with PIS categories in all four follow-ups. The QMGS, MG-ADL, and MG-QOL15 scores in patients belonging to each PIS category at each follow-up were compared. The sustainability of the R/MM status was examined and correlated with real-time R/MM status at follow-ups.
At baseline, 376 patients could be classified, including 55 as R (14.2%), 209 as MM (54.0%), and 112 as SI (28.9%). In the whole cohort, 68.8-89.7%, 71-76.7% and 19.8-77.1% of the patients classified into real-time R, MM, and SI categories remained unchanged in each follow-up compared with the previous follow-up. The proportion of patients belonging to each real-time or sustained R/MM status at the three follow-ups was 89.7-92.1 or 60.8-67. In the SA cohort, at least 86.4% of the baseline R/MM patients remained in R/MM status till 12 months. There were no differences in keeping real-time R/MM status at 6 or 12 months between patients with and without sustained R/MM status at 3 and 6 months. There were differences in the QMGS, MG-ADL, and MG-QOL15 scores among patients belonging to each real-time category at baseline and follow-ups, ranking as R < MM < SI. The same trend was observed in patients belonging to each sustained PIS category with smaller scores than the same items of real-time categories.
The sustainability of the R/MM status was confirmed. The R/MM status indicated a stable state of MG. The QMGS, MG-ADL, and MG-QOL15 scores may provide a quantitative reference for these PIS.
Biomarkers that assess treatment response for patients with the autoimmune disorder, myasthenia gravis (MG), have not been evaluated to a significant extent. We hypothesized the pro-inflammatory ...cytokine, osteopontin (OPN), may be associated with variability of response to glucocorticoids (GCs) in patients with MG. A cohort of 250 MG patients treated with standardized protocol of GCs was recruited, and plasma OPN and polymorphisms of its gene, secreted phosphoprotein 1 (
), were evaluated. Mean OPN levels were higher in patients compared to healthy controls. Carriers of rs11728697*T allele (allele definition: one of two or more alternative forms of a gene) were more frequent in the poorly GC responsive group compared to the GC responsive group indicating an association of rs11728697*T allele with GC non-responsiveness. One risk haplotype (AGTACT) was identified associated with GC non-responsiveness compared with GC responsive MG group. Genetic variations of
were found associated with the response to GC among MG patients.
Background: Myasthenia gravis (MG) is an autoimmune disorder with a chronic fluctuating course. The outcome measures encapsulate disease severity, functional impact at diagnosis, and objective ...evaluation of clinical benefit from therapeutic interventions.Aims and Objective: To assess the disease severity, correlation between various outcome measures, and to evaluate the short-term outcome at 3 months and 6 months in a cohort of MG patients.Materials and Methods: Quantitative myasthenia gravis (QMG) score, myasthenia gravis composite (MGC) score, and myasthenia gravis quality of life-15 (MG-QoL-15) score were applied to 54 patients at first visit, 3 months and 6 months follow-up.Results: Mean quality of life-15 (QoL-15) score at base line was 15.241. Mean QMG and MGC scores at baseline were 14.63 ± 8.37 and 15.87 ± 9.14, respectively. QMG score showed a strong positive correlation with both MGC and MG-QoL-15 scores. QMG and MGC scores showed a moderate correlation with acetylcholine receptor antibody (AChR Ab) titers. Mean QMG at follow-up was 9.95 ± 5.49 at 3 months and 6.74 ± 4.74 at 6 months. Mean MGC at follow-up was 10.75 ± 5.58 at 3 months and 6.51 ± 4.36 at 6 months. Conclusion: The combination of physician-evaluated and patient-reported outcome measures provided a more discerning picture of patient status and response to treatment. Incorporating MG outcome measures into clinical practice would aid in modulating therapies.
Since there has been no conclusive evidence regarding the treatment of ocular myasthenia, treatment guidelines were recently issued by the European Federation of Neurological Societies/European ...Neurological Society (EFNS/ENS). However, the therapeutic outcomes concerning the quality-of-life (QOL) of patients with ocular myasthenia are not yet fully understood.
We investigated the therapeutic outcomes of patients with purely ocular myasthenia in a multicenter cross-sectional survey in Japan. To evaluate the severity of ocular symptoms, we used the ocular-quantitative MG (QMG) score advocated by Myasthenia Gravis Foundation of America. We used the Japanese translated version of the MG-QOL15, a self-appraised scoring system.
Of 607 myasthenia gravis (MG) patients with an observation-duration of illness ≥ 2 years, the cases of 123 patients (20%) were limited to ocular muscles (purely ocular myasthenia). During the entire clinical course, 81 patients experienced both ptosis and diplopia, 36 had ptosis alone, and six had diplopia alone. Acetyl-cholinesterase inhibitors and prednisolone were used in 98 and 52 patients, respectively. Treatment improved ocular symptoms, with the mean reduction in ocular-QMG score of 2.3 ± 1.8 points. However, 47 patients (38%) failed to gain minimal manifestation or a better status. Patients with unfavorable outcomes also self-reported severe QOL impairment. Multivariate analyses showed that the pretreatment ocular-QMG score was associated with unfavorable outcomes, but not associated with the patient's QOL.
A treatment strategy designed in accord with a patient's ocular presentation must be considered in order to improve ocular symptoms and the patient's QOL.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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