Quantitative Myasthenia Gravis Research Articles

Efgartigimod and Ravulizumab for Treating Acetylcholine Receptor Auto-antibody-Positive (AChR-Ab+) Generalized Myasthenia Gravis: Indirect Treatment Comparison.

Efgartigimod and ravulizumab, both approved for treating acetylcholine receptor auto-antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG), have not been directly compared. This paper assessed comparative effects of efgartigimod vs. ravulizumab for treating adults with AChR-Ab+gMG using indirect treatment comparison methods. The matching-adjusted indirect comparison used data from two randomized trials of adult men and women. The ADAPT (efgartigimod vs. placebo; individual patient data available) population was reweighted to match the CHAMPION (ravulizumab vs. placebo; index study; aggregate data available) population. The relative effect of efgartigimod versus placebo was estimated in this reweighted population and compared with the observed ravulizumab versus placebo effect to estimate the efgartigimod versus ravulizumab effect. The outcomes were Myasthenia Gravis Activities of Daily Living (MG-ADL), QuantitativeMyasthenia Gravis (QMG), and Myasthenia Gravis Quality of Life 15-item-revised scale (MG-QoL15r) assessed as cumulative effect (area under the curve; AUC) over 26 weeks (primary) and change from baseline at 4 weeks and time of best response (week 4 for efgartigimod; week 26 for ravulizumab). For MG-QoL15r, efgartigimod had a statistically significant improvement compared with ravulizumab over 26 weeks [mean difference (95% confidence interval): -52.6 (-103.0, -2.3)], at week 4 [-4.0 (-6.6, -1.4)], and at time of best response [-3.9 (-6.5, -1.3)]. Efgartigimod had a statistically significant improvement over ravulizumab in MG-ADL at week 4 [-1.9 (-3.3, -0.5)] and at time of best response [-1.4 (-2.8, 0.0)] and in QMG at week 4 [-3.2 (-5.2, -1.2)] and at time of best response [-3.0 (-5.0, -1.0)]. For AUC over 26 weeks, improvements were not significantly different between efgartigimod and ravulizumab for MG-ADL [-8.7 (-36.1, 18.8)] and QMG [-13.7 (-50.3, 22.9)]. Efgartigimod may provide a faster and greater improvement over 26 weeks in quality of life than ravulizumab in adults with AChR-Ab+gMG. Efgartigimod showed faster improvements in MG-ADL and QMG than ravulizumab.

A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis.

This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.

Eculizumab in Adolescent Patients With Refractory Generalized Myasthenia Gravis: A Phase 3, Open-Label, Multicenter Study

BackgroundThis study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG). MethodsAdolescents aged 12 to 17 years with refractory anti-acetylcholine receptor (AChR) antibody-positive gMG received eculizumab (weekly induction [one to two doses of 600 mg or four doses of 900 mg] followed by maintenance doses [300 to 1200 mg] every two weeks for up to 26 weeks) in a phase 3, open-label multicenter study (NCT03759366). Change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score (primary end point) and secondary end points including Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score, Myasthenia Gravis Composite score, Myasthenia Gravis Foundation of America postintervention status, EuroQol 5-Dimensions (Youth) and Neurological Quality-of-Life Pediatric Fatigue questionnaire scores, as well as pharmacokinetics, pharmacodynamics, and safety, were recorded. ResultsEleven adolescents (mean ± S.D. age 14.8 ± 1.8 years) were enrolled; 10 completed the primary evaluation period. Least-squares mean changes from baseline at week 26 were −5.8 (standard error [SE] 1.2; P = 0.0004) for QMG total score and −2.3 (SE 0.6; P = 0.0017) for MG-ADL total score. Overall, the primary and all secondary efficacy end point analyses met statistical significance from the first assessment and were sustained throughout. Complete terminal complement inhibition was sustained through 26 weeks in all patients. Treatment-emergent adverse events were all mild/moderate and predominantly unrelated to eculizumab. ConclusionsEculizumab was effective in reducing disease burden and was well tolerated in adolescents with refractory AChR antibody-positive gMG.

Intravenous methylprednisolone therapy for ocular myasthenia gravis: A retrospective study

AbstractBackgroundAlthough intravenous methylprednisolone pulse (IVMP) therapy has been recommended for ocular myasthenia gravis (OMG), the evidence is limited.AimWe aimed to investigate the efficacy and safety of IVMP for OMG.MethodsThe patients with OMG were chosen retrospectively from May 2010 to December 2022. The therapeutic effects between IVMP‐treated and non‐IVMP‐treated groups were determined by ∆ocular quantitative MG (QMG) score and the ∆ocular MG activities of daily living profile (MG‐ADL) score, which is the disparities of the scores between before and after 1 month of drug administration; and Myasthenia Gravis Foundation of America post‐intervention status at 1, 3, 6, and 12 months.ResultsThere were 26 patients with OMG included, with the mean age of 67.2 ± 13.1 years. 13 of the 26 people with OMG received IVMP and subsequent low‐dose immunotherapies. The ∆ocular QMG and ∆ocular MG‐ADL scores were significantly higher in the IVMP group of 3 (1.5, 4) and 3 (2, 4.5) than in the non‐IVMP group of 1.5 (0, 3) and 1 (0, 2), p = 0.038 and p = 0.0027, respectively. The rates of minimal manifestation or better status in post‐intervention status at 1 and 12 months were also considerably higher in the IVMP group of 77% and 92% compared with the non‐IVMP group of 0% and 23%, p = 0.0001 and 0.001. There were no serious side effects discovered.ConclusionIVMP induction therapy can quickly and safely improve symptoms of OMG, and subsequent low‐dose immunotherapy can keep symptoms at bay for 12 months.

Expert consensus recommendations for improving and standardising the assessment of patients with generalised myasthenia gravis.

Regular and consistent disease assessment could provide a clearer picture of burden in generalised myasthenia gravis (gMG) and improve patient care; however, the use of assessment tools in practice lacks standardisation. This modified Delphi approach was taken to review current evidence on assessment tool use in gMG and develop expert-derived consensus recommendations for good practice. A European expert panel of 15 experienced gMG neurologists contributed to development of this consensus, four of whom formed a lead Sub-committee. The PICO (Population, Intervention, Control, Outcomes) framework was used to define six clinical questions on gMG assessment tools, a systematic literature review was conducted, and evidence-based statements were developed. According to a modified Delphi voting process, consensus was reached when ≥70% of the experts rated agreement with a statement as ≥8 on a scale of 1-10. Eighteen expert- and evidence-based consensus statements based on six themes were developed. Key recommendations include: consistent use of the Myasthenia Gravis Activities of Daily Living score (MG-ADL) across clinical settings, followed by a simple question (e.g., Patient Acceptable Symptom State [PASS]) or scale to determine patient satisfaction in clinical practice; use of a Quantitative Myasthenia Gravis [QMG] or quality of life [QoL] assessment when the MG-ADL indicates disease worsening; and consideration of symptom state to determine the timing and frequency of recommended assessments. Expert panel consensus was reached on all 18 statements after two voting rounds. This process provided evidence- and expert consensus-based recommendations for the use of objective and subjective assessment tools across gMG research and care to improve management and outcomes for patients.

The efficacy and safety of FcRn inhibitors in patients with myasthenia gravis: a systematic review and meta-analysis.

Myasthenia gravis (MG) is an autoimmune disease that causes local or generalized muscle weakness. Complement inhibitors and targeting of the neonatal Fc receptor (FcRn) to block IgG cycling are two novel and successful mechanisms. PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before May 18, 2023. Review Manager 5.3 software was used to assess the data. We pooled 532 participants from six randomized controlled trials (RCTs). Compared to the placebo, the FcRn inhibitors were more efficacy in Myasthenia Gravis Activities of Daily Living (MG-ADL) (MD = - 1.69 [- 2.35, - 1.03], P < 0.00001), MG-ADL responder (RR = 2.01 [1.62, 2.48], P < 0.00001), Quantitative Myasthenia Gravis (QMG) (MD = - 2.45 [- 4.35, - 0.55], P = 0.01), Myasthenia Gravis Composite (MGC) (MD = - 2.97 [- 4.27, - 1.67], P < 0.00001), 15-item revised version of the Myasthenia Gravis Quality of Life (MGQoL15r) (MD = - 2.52 [- 3.54, - 1.50], P < 0.00001), without increasing the risk of safety. The subgroup analysis showed that efgartigimod was more effective than placebo in MG-ADL responders. Rozanolixizumab was more effective than the placebo except in QMG, and batoclimab was more effective than the placebo except in MG-ADL responder. Nipocalizumab did not show satisfactory efficacy in all outcomes. With the exception of rozanolixizumab, all drugs showed non-inferior safety profiles to placebo. FcRn inhibitors have good efficacy and safety in patients with MG. Among them, efgartigimod and nipocalimab were effective without causing an increased safety risk. Rozanolixizumab, despite its superior efficacy, caused an increased incidence of adverse events. Current evidence does not suggest that nipocalimab is effective in patients with MG.

Constructing and Validating a Nomogram Model for Short-Term Prognosis of Patients with AChR-Ab+ GMG.

This study aimed to establish and validate a nomogram prognostic model for predicting short-term efficacy of acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (GMG). A retrospective observational study was conducted at the First Hospital of Shanxi Medical University, enrolling patients diagnosed with AChR-Ab+ GMG from May 2020 to September 2022. The primary outcome was the change in the Myasthenia Gravis Foundation of America (MGFA) post-intervention status after 6months of standard treatment. Predictive factors were identified through univariate and multivariate logistic regression analyses, with significant factors incorporated into the nomogram. The bootstrap test was used for internal validation of the nomogram model. Model performance was assessed using calibration curves, receiver-operating characteristic curve analysis, and decision curve analysis (DCA). A total of 90 patients were enrolled, of whom 30 achieved unchanged or worse status after 6months of standard therapy. Univariate logistic regression analysis showed that quantitative myasthenia gravis score, gender, body mass index, course of disease, hemoglobin levels, and white blood cell counts were six potential predictors. These factors were used for multivariate logistic regression analysis, and a nomogram was constructed. The calibration curve showed that the predicted value was in good agreement with the actual value (p = 0.707), and the area under the curve value (0.792, 95% CI 0.686-0.899) indicated good discrimination ability. DCA suggests that this model has potential clinical application value. The constructed nomogram, based on key patient indicators, shows promise as a clinically useful tool for predicting the short-term efficacy of treatment of AChR-Ab+ GMG. Validation in larger, multicenter cohorts is needed to further substantiate its applicability.

Clinicopathological predictors of postoperative long-term myasthenic status in resected thymoma with myasthenia gravis.

Surgical patients with thymoma and myasthenia gravis (MG) must have their MG status and oncological outcomes critically monitored. We aimed to identify clinicopathological predictors of the postoperative MG status. We conducted a retrospective review of 40 consecutive surgical patients with MG-related thymomas between 2002 and 2020. The quantitative myasthenia gravis score (QMGS) and Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS) were used to evaluate postoperative MG status. All patients underwent extended total thymectomy. The most common WHO type was type B2 (32%), while 65% of patients had type B1-B3 and 35% had type A-AB thymomas. Eleven patients (28%) achieved controlled MG status in MGFA-PIS 6months after surgery. This controlled status was observed more frequently in type A-AB than in B1-B3 (57% vs. 12%, p = 0.007). In a multivariate analysis, WHO type (A-AB or B1-B3) was an independent predictor of worsening episodes of MG based on the QMGS (Type B1-B3, hazard ratio: 3.23, 95% confidence interval: 1.12-9.25). At the last follow-up, 23 patients (58%) achieved controlled MG status. The 5-year overall survival rate of all patients was 93.7%. The WHO type of thymoma is an informative predictor of postoperative MG status in patients with MG-related thymoma.

Efficacy of ravulizumab in patients with generalized myasthenia gravis by time from diagnosis: A post hoc subgroup analysis of the CHAMPION MG study.

The CHAMPION MG study demonstrated that ravulizumab significantly improved Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores versus placebo in adults with acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ gMG). This post hoc analysis aimed to assess these outcomes by time from MG diagnosis. Changes from baseline to week 26 in MG-ADL and QMG total scores were analyzed by time from MG diagnosis to study entry (≤2 vs. >2 years). Within each subgroup, least-squares (LS) mean changes for ravulizumab and placebo were compared using mixed models for repeated measures. In ravulizumab-treated patients, differences in LS mean (standard error of the mean) changes from baseline to week 26 were not statistically significant in the ≤2-years subgroup versus the >2-years subgroup for MG-ADL (-4.3 [0.70] vs. -2.9 [0.37]; p = .0511) or QMG (-4.3 [0.94] vs. -2.5 [0.50]; p = .0822) scores. No clear trends were observed in the placebo group. LS mean changes from baseline were significantly greater for ravulizumab versus placebo in both the ≤2 and >2 years from diagnosis subgroups for MG-ADL and QMG scores (all p < .05). The difference in treatment effect between the ≤2-years and >2-years subgroups was not statistically significant. No clinically meaningful between-subgroup differences in treatment-emergent adverse events were observed in ravulizumab-treated patients. Ravulizumab treatment improved clinical outcomes for patients with AChR+ gMG regardless of time from diagnosis. A numerical trend was observed favoring greater treatment effect with earlier versus later treatment after diagnosis. Further studies are required for confirmation.

The Efficacy and Safety of Different Targeted Drugs for the Treatment of Generalized Myasthenia Gravis: A Systematic Review and Bayesian Network Meta-analysis.

The treatment of generalized myasthenia gravis (gMG) has been transformed by the development and approval of new targeted therapies. This analysis aimed to rank and compare the new therapies for gMG using efficacy and safety data from randomized controlled trials (RCTs). We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (up to November 2022) for RCTs of targeted drugs for gMG. We used a Bayesian random-effects network meta-analysis (NMA) model and a Markov chain Monte Carlo (MCMC) model for statistical analysis. The primary outcome was the change in quantitative myasthenia gravis score (QMGS) from baseline, while the secondary outcome was the risk ratio (RR) of adverse events (AEs) during treatment. The surface under the cumulative ranking curve (SUCRA) was used to rank these targeted drugs, with higher SUCRA values indicating better efficacy or lower likelihood of AEs. In total, 13 studies (872 subjects) were included in this analysis evaluating 10 targeted drugs (batoclimab, belimumab, CFZ533, eculizumab, efgartigimod, nipocalimab, rituximab, ravulizumab, rozanolixizumab, and zilucoplan). With regards to the primary outcome, batoclimab [standardized mean difference (SMD), - 1.61; 95% credible interval (CrI), - 2.78, - 0.43] significantly reduced QMGS in patients with gMG when compared with placebo and was ranked as the most efficacious drug. Ranked second and third were eculizumab (SMD, - 0.67; 95% CrI, 1.43, 0.01) and zilucoplan (SMD, - 0.54; 95% CrI, - 1.56, 0.46), respectively. Nipoclimab (SMD, - 0.02; 95% CrI, - 1.04, 1.00) had the worst efficacy and ranked last among all targeted drugs. In our study, except for batoclimab, there was no statistically significant difference in the reduction of patient QMGS for the remaining targeted agents compared with placebo. With regards to the secondary outcomes, only batoclimab (RR, 0.19; 95% CrI, 0, 0.97) led to a significant reduction in the incidence of AEs when compared with the placebo. Belimumab (RR, 0.85; 95% CrI, 0.57, 1.19), CFZ533 (RR, 0.95; 95% CrI, 0.72, 1.25), eculizumab (RR, 0.99; 95% CrI, 0.85, 1.21), and efgartigimod (RR, 0.93; 95% CrI, 0.76, 1.15) also led to a lower incidence of AEs, although these effects were not significantly different from the placebo. Batoclimab had the best efficacy and safety for the treatment of gMG and was ranked first out of the 10 targeted drugs included in this study. Eculizumab was ranked second, and nipocalimab had the worst efficacy. With the exception of batoclimab,the incidence of AEs for the remaining drugs was not statistically significantly different from placebo. We note, however, that wide CrIs reflect the uncertainty in this analysis owing to the small number of available studies and low numbers of study participants; moreover, batoclimab had the widest CrI of all drugs in this analysis. More well-designed studies with long-term follow-up are needed to further evaluate and compare the efficacy and safety of these drugs in the future.

Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis.

ADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG). ADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions (one 10 mg/kg infusion per week). Initiation of subsequent treatment cycles was individualized based on clinical evaluation. Safety endpoints included incidence and severity of adverse events. Efficacy endpoints assessed disease severity using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. As of January 2022, 151 participants had rolled over to ADAPT+ and 145 had received ≥1 dose of efgartigimod, of whom, 111 (76.6%) were AChR-Ab+ and 34 (23.4%) were AChR-Ab-. Mean study duration (treatment plus follow-up) was 548 days, and participants received up to 17 treatment cycles, corresponding to 217.6 participant-years of exposure. In the overall population, 123 (84.8%) participants reported ≥1 treatment-emergent adverse event; most frequent were headache (36 [24.8%]), COVID-19 (22 [15.2%]), and nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) in mean MG-ADL and QMG scores was seen as early as 1 week following the first infusion across multiple cycles in AChR-Ab+ and AChR-Ab- participants. Maximal MG-ADL and QMG improvements aligned with onset and magnitude of total IgG and AChR-Ab reductions. For AChR-Ab+ participants at any time point in each of the first 10 treatment cycles, more than 90% had a maximum reduction of ≥2 points (CMI) in MG-ADL total score; across the 7 cycles in which QMG was measured, 69.4% to 91.3% of participants demonstrated a maximum reduction of ≥3 points (CMI) in QMG total score. Many participants demonstrated improvements well beyond CMI thresholds. In AChR-Ab+ participants with ≥1 year of combined follow-up between ADAPT and ADAPT+, mean number of annualized cycles was 4.7 per year (median [range] 5.0 [0.5-7.6]). Results of ADAPT+ corroborate the substantial clinical improvements seen with efgartigimod in ADAPT and support its long-term safety, tolerability, and efficacy, as well as an individualized dosing regimen for treatment of gMG. https://classic.clinicaltrials.gov/ct2/show/NCT03770403, NCT03770403.

Responsiveness to Tocilizumab in Anti-Acetylcholine Receptor-Positive Generalized Myasthenia Gravis.

Tocilizumab, a humanized IL-6R monoclonal antibody, has been used in autoimmune diseases closely related to humoral immunity. This report aims to evaluate the efficacy and safety in patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG). We performed a prospective, open-label, single-arm study in patients with gMG in a 48-week follow-up. All patients were AChR+ and were given tocilizumab by intravenous infusion at a dose of 8 mg/kg at intervals of 4 weeks. The primary endpoint was mean change from baseline in quantitative MG (QMG) score at week 12. The secondary endpoints were mean changes from baseline in MG activities of daily living (MG-ADL) score, AChR-ab titers, and the dosage of oral prednisone at week 12. At week 48, QMG, MG-ADL, and the use of prednisone were also evaluated. Fourteen gMG patients were enrolled and all of them completed the study. Tocilizumab treatment started 8 (4-192) months after the onset of gMG. During tocilizumab treatment, the QMG score was significantly decreased from 15.5 (interqualile range, 9-26) at baseline to 4 (0-9) at week 12 (p < 0.001). The change of ADL was decreased from 14.5(11-19) at baseline to 4 (0-19) at week 12 (p < 0.001) and the change of AChR-ab titers from 15 (7.5-19) at baseline to 6.8 (11.6-4.3) at week 12 (p < 0.001). The dosage of prednisone decreased from baseline 60 (20-65) mg/d to 30 (30-50) mg/d at week 12 (p < 0.001). By the end of the study, the QMG score was 2 (0-7) and MG-ADL score was 1.5 (0-6). 12 (85.7%) patients achieved minimal manifestations. 4 (28.6%) patients were able to discontinue prednisone. No patients experienced exacerbation at the end of the study. No serious adverse events were observed during follow-up. Tocilizumab treatment was associated with a good clinical response and safety over a 48-week observation period, as evidenced by significant improvements in QMG and MG-ADL.

Effectiveness and safety of telitacicept for refractory generalized myasthenia gravis: a retrospective study.

Refractory generalized myasthenia gravis (GMG) remains a substantial therapeutic challenge. Telitacicept, a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein, holds promise for interrupting the immunopathology of this condition. This study retrospectively assessed the effectiveness and safety of telitacicept in patients with refractory GMG. A single-center retrospective study. Patients with refractory GMG receiving telitacicept (160 mg/week or biweekly) from January to September in 2023 were included. We assessed effectiveness using Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS), myasthenia gravis treatment status and intensity (MGSTI), quantitative myasthenia gravis (QMG), and MG-activity of daily living (ADL) scores, alongside reductions in prednisone dosage at 3- and 6-month intervals. Safety profiles were also evaluated. Sixteen patients with MGFA class II-V refractory GMG were included, with eight females and eight males. All patients were followed up for at least 3 months, and 11 patients reached 6 months follow-up. At the 3-month evaluation, 75% (12/16) demonstrated clinical improvement with MGFA-PIS. One patient achieved pharmacological remission, two attained minimal manifestation status, and nine showed functional improvement; three remained unchanged, and one deteriorated. By the 6-month visit, 90.1% (10/11) sustained significant symptomatic improvement. MGSTI scores and prednisone dosages significantly reduced at both follow-ups (p < 0.05). MG-ADL and QMG scores showed marked improvement at 6 months (p < 0.05). The treatment was well tolerated, with no severe adverse events such as allergy or infection reported. Our exploratory investigation suggests that telitacicept is a feasible and well-tolerated add-on therapy for refractory GMG, offering valuable clinical evidence for this novel treatment option.

Há declínio na fala de pacientes com Miastenia Gravis ao longo de 4 anos?

ABSTRACT Purpose To compare the speech and voice patterns of myasthenia gravis (MG) patients over four years, and correlate the results with clinical aspects of the disease. Methods Data was collected for 4 years. The clinical assessment tools included the Quantitative Myasthenia Gravis (QMG) score, the Myasthenia Gravis Foundation of America (MGFA) clinical classification, and the Myasthenia Gravis Quality of Life 15-item Scale (MG-QoL). To assess speech, the recorded speaking tasks were analyzed acoustically and given auditory-perceptual ratings. Sex (equal distribution) and age (p=0.949) were used as matching criteria in the final sample, which consisted of 10 individuals in the MG group (MGG) and 10 individuals in the control group (CG). Results After 4 years, the MG participants presented stable health status, increased mild and moderate dysarthria (from 40% to 90% of the subjects), and a significant deterioration in the respiration, phonation, and articulation subsystems. The acoustic analysis showed a decline in articulatory patterns (speech rate p=0.047, articulation rate p=0.007, mean syllable duration p=0.007) and vocal quality (increased jitter p=0.022). In the follow-up comparison, there was a significant difference between the phonation variables (shimmer and harmonic-to-noise ratio) of the MGG and CG. Conclusion The MG patients presented a decline in speech over four years and an increase in mild and moderate dysarthria. Despite presenting stable health status, their respiratory, phonatory, and articulatory subsystems worsened. There was no correlation between speech patterns and clinical characteristics of the disease (severity and motor scale).

Depression: A Contributing Factor to the Clinical Course in Myasthenia Gravis Patients.

Background and Objectives: The association between myasthenia gravis (MG) and depression is intricate and characterized by bidirectional causality. In this regard, MG can be a contributing factor to depression and, conversely, depression may worsen the symptoms of MG. This study aimed to identify any differences in the progression of the disease among patients with MG who were also diagnosed with depression as compared to those without depression. Our hypothesis focused on the theory that patients with more severe MG symptoms may have a higher likelihood of suffering depression at the same time. Materials and Methods: One hundred twenty-two male and female patients (N = 122) aged over 18 with a confirmed diagnosis of autoimmune MG who were admitted to the Neurology II department of Myasthenia Gravis, Clinical Institute Fundeni in Bucharest between January 2019 and December 2020, were included in the study. Patients were assessed at baseline and after six months. The psychiatric assessment of the patients included the Hamilton Depression Rating Scale-17 items (HAM-D), and neurological status was determined with two outcome measures: Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Life (MG-ADL). The patients were divided into two distinct groups as follows: group MG w/dep, which comprised 49 MG patients diagnosed with depressive disorder who were also currently receiving antidepressant medication, and group MG w/o dep, which consisted of 73 patients who did not have depression. Results: In our study, 40.16% of the myasthenia gravis (MG) patients exhibited a comorbid diagnosis of depression. Among the MG patients receiving antidepressant treatment, baseline assessments revealed a mean MG-ADL score of 7.73 (SD = 5.05), an average QMG score of 18.40 (SD = 8.61), and a mean Ham-D score of 21.53 (SD = 7.49). After a six-month period, a statistically significant decrease was observed in the MG-ADL (2.92, SD = 1.82), QMG (7.15, SD = 4.46), and Ham-D scores (11.16, SD = 7.49) (p < 0.0001). These results suggest a significant correlation between MG severity and elevated HAM-D depression scores. Regarding the MG treatment in the group with depression, at baseline, the mean dose of oral corticosteroids was 45.10 mg (SD = 16.60). Regarding the treatment with pyridostigmine, patients with depression and undergoing antidepressant treatment remained with an increased need for pyridostigmine, 144.49 mg (SD = 51.84), compared to those in the group without depression, 107.67 mg (SD = 55.64, p < 0.001). Conclusions: Our investigation confirms that the occurrence of depressive symptoms is significantly widespread among individuals diagnosed with MG. Disease severity, along with younger age and higher doses of cortisone, is a significant factor associated with depression in patients with MG. Substantial reductions in MG-ADL and QMG scores were observed within each group after six months, highlighting the effectiveness of MG management. The findings suggest that addressing depressive symptoms in MG patients, in addition to standard MG management, can lead to improved clinical outcomes.

Therapeutic effect of ofatumumab in patients with myasthenia gravis: immunoregulation of follicular T helper cells and T helper type 17 cells.

This study aimed to study the therapeutic effects of ofatumumab in patients with myasthenia gravis (MG) in addition to the immunomodulatory effects on peripheral follicular T helper (Tfh) cells and T helper type 17 (Th17) cells. Thirty-one patients with anti-acetylcholine receptor (AChR) antibody-positive MG were included in this study. At weeks 0, 1, 2, and 4, an initial dose of 20 mg of ofatumumab was injected subcutaneously, with a 2-month follow-up after completing this first cycle. At baseline, 1 month, and 3 months, we assessed the Quantitative MG (QMG), 15-item MG-Quality of Life (MG-QOL15), and MG-Activities of Daily Living (MG-ADL) scales and measured the frequencies of Tfh, Th17, and B cells and the levels of anti-AChR antibody, IL-6, IL-21, and IL-17 in the peripheral blood. At 1 month and 3 months, the QMG, MG-QOL15, and MG-ADL scores were all significantly reduced. At 3 months, doses of prednisone were reduced by an average of 37%. Decreased frequencies of Tfh and Th17 cells, depletion of B cells, and reduced levels of IL-6, IL-21, and IL-17 were all observed at 1 month or 3 months. Therefore, the therapeutic effect of ofatumumab could be detected after one cycle of treatment, which was maintained for 2 months. The immunomodulatory effect of ofatumumab during the observation period may involve depletion of B cells, reduction of Tfh and Th17 cells frequencies, and reduced levels of IL-6, IL-21, and IL-17. The findings provide novel data for the potential application of ofatumumab in MG.

Plasma Exchange versus Intravenous Immunoglobulin in Worsening Myasthenia Gravis: A Systematic Review and Meta-Analysis with Special Attention to Faster Relapse Control.

Currently used rescue interventions to prevent rapid myasthenic deterioration are plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). We investigated the evidence to determine whether the two methods were interchangeable or whether one was superior to the other. This review was registered on PROSPERO (CRD42021285985). Only randomized controlled trials (RCTs) comparing the efficacy and safety of PLEX and IVIG in patients with moderate-to-severe myasthenia gravis (MG) were included. Five major databases were systematically searched (PubMed, CENTRAL, Embase, Scopus, and Web of Science). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for adverse events and mean differences (MD) for changes in quantitative myasthenia gravis scores (QMG). Three RCTs met the inclusion criteria. Two investigating 114 patients in total were eligible for meta-analysis to analyze efficacy and safety. For the change in QMG score, the MD was -2.8 (95% CI: -5.614-0.113), with PLEX performing better. For adverse events, an OR of 1.04 was found (95% CI: 0.25-4.27). This study demonstrated a low risk of bias in evaluating treatment efficacy but indicated a high risk of bias in assessing procedural safety outcomes. Although the results did not show any significant difference, there was a tendency indicating faster efficacy of PLEX in the first two weeks of treatment. In such a critical clinical condition, this tendency may be clinically meaningful, but further studies should clarify this benefit.

Promising efficacy of Low-Dose rituximab in Muscle specific kinase antibody positive Myasthenia Gravis

AimsThe study aims to evaluate the efficacy of low dose rituximab (RTX) in patients with muscle-specific kinase antibody positive myasthenia gravis (MuSK-MG). MethodsThis is a single-center, retrospective study. A total of 10 patients with MuSK-MG were admitted to the Department of Neurology, First Hospital, Shanxi Medical University, between April 2021 to April 2023. Of them, 9 patients had been treated with low dose RTX (500 mg every 6 month) and recruited in this study. The clinical information, including the severity before and after RTX treatment, were collected from the medical records. Clinical effectiveness was assessed by Myasthenia Gravis Foundation of America (MGFA)-postintervention status (PIS), MG-related activities of daily living (MG-ADL), Quantitative Myasthenia Gravis (QMG) scores, Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r), dosage of steroid at the end of follow up. ResultsAll nine patients showed clinical improvement at the final follow-up after low-dose RTX treatment. The mean dose of prednisolone decreased significantly from 50 mg at baseline to 18.33 mg at the last follow-up (z = -3.417, p = 0.001). The administration of low-dose RTX treatment led to significant improvements in ADL levels (Z = -2.675, P < 0.01), QMG score levels (Z = -2.371, P < 0.05) and QOL-15r levels (Z = -2.547, P < 0.01) at last visit. ConclusionLow-dose RTX is effective for treating MuSK-MG patients. Longer-term follow-up and larger-scale studies are needed to provide further evidence.

Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study.

Generalized myasthenia gravis (gMG) is a rare, chronic, neuromuscular autoimmune disease mediated by pathogenic immunoglobulin G (IgG) autoantibodies. Patients with gMG experience debilitating muscle weakness, resulting in impaired mobility, speech, swallowing, vision and respiratory function. Efgartigimod is a human IgG1 antibody Fc fragment engineered for increased binding affinity to neonatal Fc receptor. The neonatal Fc receptor blockade by efgartigimod competitively inhibits endogenous IgG binding, leading to decreased IgG recycling and increased degradation resulting in lower IgG concentration. The safety and efficacy of efgartigimod were evaluated in the ADAPT study. Key efficacy outcome measures included Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Efgartigimod demonstrated significant improvement in both the MG-ADL and QMG scores. This post hoc analysis aimed to determine whether all subdomains of MG-ADL and QMG improved with efgartigimod treatment. Individual items of MG-ADL and QMG were grouped into four subdomains: bulbar, ocular, limb/gross motor and respiratory. Change from baseline over 10 weeks in each subdomain was calculated for each group. Greater improvements from baseline were seen across MG-ADL subdomains in participants treated with efgartigimod compared with placebo. These improvements were typically observed 1 to 2 weeks after the first infusion and correlated with reductions in IgG. Similar results were observed across most QMG subdomains. These post hoc analyses of MG-ADL and QMG subdomain data from ADAPT suggest that efgartigimod is beneficial in improving muscle function and strength across all muscle groups, leading to the observed efficacy in participants with gMG.

Rituximab as a sole steroid-sparing agent in generalized myasthenia gravis: Long-term outcomes.

Rituximab, a B-cell depleting monoclonal antibody, represents an option for the treatment of refractory myasthenia gravis (MG). Its use is more established in muscle-specific tyrosine kinase positive (MuSK +) patients, while its role in managing acetylcholine receptor positive (AChR +), or double seronegative (DSN) patients, remains less clear. This study evaluates the long-term effectiveness and safety of rituximab in MG of various serotypes. We conducted an open-label study of MG patients receiving rituximab. Adults with generalized refractory MG, either anti-AChR + or DSN, and anti-MuSK + , refractory or not, who had follow-up > 12months were selected. Change in quantitative myasthenia gravis (QMG) score at last follow-up, compared with baseline was a primary outcome, as well as factors affecting response to treatment. Secondary outcomes included, long-term safety, the steroid-sparing effect and relapse rates post-rituximab. Thirty patients (16 anti-AChR + , 6 anti-MuSK + , 8 DSN) followed for a mean of 33.3months were included. Mean scores pre-rituximab compared to last follow-up significantly decreased (p < 0.001), from 11 ± 4.1 to 4.3 ± 3.8, and from 1.9 to 0.3 regarding QMG and relapse rate per patient/year, respectively, while in 93.1% a daily steroid dose ≤ 10mg was achieved. Antibody status was the only factor independently influencing several endpoints. Throughout the study period no crises or deaths occurred. The present study supports that rituximab is an effective and well tolerated treatment for refractory anti-AChR + and DSN MG patients, while anti-MuSK + remains the group experiencing the greater benefits.