Psychometric Properties of the Quantitative Myasthenia Gravis Score and the Myasthenia Gravis Composite Scale.
ABSTRACT: The Quantitative Myasthenia Gravis Score and the Myasthenia Gravis Composite are two commonly used outcome measures in Myasthenia Gravis. So far, their measurement properties have not been compared, so we aimed to study their psychometric properties using the Rasch model.251 patients with stable myasthenia gravis were assessed with both scales, and 211 patients returned for a second assessment. We studied fit to the Rasch model at the first visit, and compared item fit, thresholds, differential item functioning, local dependence, person separation index, and tests for unidimensionality. We also assessed test-retest reliability and estimated the Minimal Detectable Change.Neither scale fit the Rasch model (X2p?< ?0.05). The Myasthenia Gravis Composite had lower discrimination properties than the Quantitative Myasthenia Gravis Scale (Person Separation Index: 0.14 and 0.7). There was local dependence in both scales, as well as differential item functioning for ocular and generalized disease. Disordered thresholds were found in 6(60%) items of the Myasthenia Gravis Composite and in 4(31%) of the Quantitative Myasthenia Gravis Score. Both tools had adequate test-retest reliability (ICCs?>0.8). The minimally detectable change was 4.9 points for the Myasthenia Gravis Composite and 4.3 points for the Quantitative Myasthenia Gravis Score.Neither scale fulfilled Rasch model expectations. The Quantitative Myasthenia Gravis Score has higher discrimination than the Myasthenia Gravis Composite. Both tools have items with disordered thresholds, differential item functioning and local dependency. There was evidence of multidimensionality in the QMGS. The minimal detectable change values are higher than previous studies on the minimal significant change. These findings might inform future modifications of these tools.
Project description:OBJECTIVE:To 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. METHODS:A 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. RESULTS:Of 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. CONCLUSIONS:Efgartigimod 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 EVIDENCE:This study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.
Project description:To study the concurrent and construct validity and test-retest reliability in the practice setting of an outcome measure for myasthenia gravis (MG).Eleven centers participated in the validation study of the Myasthenia Gravis Composite (MGC) scale. Patients with MG were evaluated at 2 consecutive visits. Concurrent and construct validities of the MGC were assessed by evaluating MGC scores in the context of other MG-specific outcome measures. We used numerous potential indicators of clinical improvement to assess the sensitivity and specificity of the MGC for detecting clinical improvement. Test-retest reliability was performed on patients at the University of Virginia.A total of 175 patients with MG were enrolled at 11 sites from July 1, 2008, to January 31, 2009. A total of 151 patients were seen in follow-up. Total MGC scores showed excellent concurrent validity with other MG-specific scales. Analyses of sensitivities and specificities of the MGC revealed that a 3-point improvement in total MGC score was optimal for signifying clinical improvement. A 3-point improvement in the MGC also appears to represent a meaningful improvement to most patients, as indicated by improved 15-item myasthenia gravis quality of life scale (MG-QOL15) scores. The psychometric properties were no better for an individualized subscore made up of the 2 functional domains that the patient identified as most important to treat. The test-retest reliability coefficient of the MGC was 98%, with a lower 95% confidence interval of 97%, indicating excellent test-retest reliability.The Myasthenia Gravis Composite is a reliable and valid instrument for measuring clinical status of patients with myasthenia gravis in the practice setting and in clinical trials.
Project description: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.
Project description:OBJECTIVE:To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. METHODS:Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed. RESULTS:Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension. INTERPRETATION:Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.
Project description:INTRODUCTION:Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scales were compared using the data from the Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy (MGTX) study. METHODS:Correlation between QMG and MG-ADL raw and change-from-baseline scores was calculated every 3?months for 60?months based on treatment groups and minimal manifestation status (MMS). RESULTS:QMG and MG-ADL change-from-baseline scores correlated significantly, with increasing strength of correlation over time, in both treatment groups. QMG and MG-ADL raw scores correlated significantly in both treatment groups, with increasing correlation only in the prednisone-alone group. Correlation between raw scores was weaker in patients who were in MMS, demonstrating a "floor effect" on the MG-ADL scale. Raw QMG scores could be modeled assuming a normal distribution, whereas raw MG-ADL scores could not be modeled this way. DISCUSSION:The floor effect and skewed distribution of the MG-ADL measure should be taken into account in the design of myasthenia gravis clinical trials.
Project description:Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone.We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period.A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003).Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).
Project description:To determine the steroid-sparing effect of methotrexate (MTX) in patients with symptomatic generalized myasthenia gravis (MG).We performed a 12-month multicenter, randomized, double-blind, placebo-controlled trial of MTX 20 mg orally every week vs placebo in 50 acetylcholine receptor antibody-positive patients with MG between April 2009 and August 2014. The primary outcome measure was the prednisone area under the dose-time curve (AUDTC) from months 4 to 12. Secondary outcome measures included 12-month changes of the Quantitative Myasthenia Gravis Score, the Myasthenia Gravis Composite Score, Manual Muscle Testing, the Myasthenia Gravis Quality of Life, and the Myasthenia Gravis Activities of Daily Living.Fifty-eight patients were screened and 50 enrolled. MTX did not reduce the month 4-12 prednisone AUDTC when compared to placebo (difference MTX - placebo: -488.0 mg, 95% confidence interval -2,443.4 to 1,467.3, p = 0.26); however, the average daily prednisone dose decreased in both groups. MTX did not improve secondary measures of MG compared to placebo over 12 months. Eight participants withdrew during the course of the study (1 MTX, 7 placebo). There were no serious MTX-related adverse events. The most common adverse event was nonspecific pain (19%).We found no steroid-sparing benefit of MTX in MG over 12 months of treatment, despite being well-tolerated. This study demonstrates the challenges of conducting clinical trials in MG, including difficulties with recruitment, participants improving on prednisone alone, and the need for a better understanding of outcome measure variability for future clinical trials.This study provides Class I evidence that for patients with generalized MG MTX does not significantly reduce the prednisone AUDTC over 12 months of therapy.
Project description:There is a pressing need for a robust rating scale for ocular myasthenia gravis (OMG). Rating scales for myasthenia gravis (MG) research have a predominant focus on generalised disease. We present results of the first dedicated rating scale for OMG: the ocular myasthenia gravis rating scale (OMGRate). The OMGRate was developed through an international collaboration between neuromuscular and neuro-ophthalmology experts in OMG. It comprises two components: a physician- examination (OMGRate-e) and a patient questionnaire (OMGRate-q).. The OMGRate was prospectively validated in patients attending a neuro-ophthalmology clinic from April 2017 to October 2018. External validity and reliability of OMGRate were evaluated using validated MG rating scales: the Myasthenia Gravis Composite (MGC), the Myasthenia Gravis Quality of Life (MG-QOL), and the ocular component from the Myasthenia Gravis Impairment Index questionnaire (MGII). Two hundred and eleven assessments were completed in 104 patients (67 males, mean age 55 y, range 18-86 y). There was very good external validity of the OMGRate: good correlation between OMGRate-e and MGC (r = 0.64, 95% confidence intervals [CI] 0.54-0.74, p < .0001); excellent correlation between OMGRate-q and MGII (r = 0.85, 95% CI 0.78-0.91, p < .0001) and good correlation between OMGRate and MG-QOL (r = 0.68, 95% CI 0.60-0.77, p < .0001). A higher correlation of OMGRate and MG-QOL compared with MGC and MG-QOL (r = 0.47, 95% CI 0.34-0.59, p < .0001) suggests that OMGRate is better able to capture significant QOL information in patients with OMG. It had excellent reliability with an intraclass correlation coefficient of 0.83 (95% CI 0.67-0.92). Feedback from examiners and patients indicated that the OMGRate was easy to use. In conclusion, OMGRate is an easy-to-use, valid and reliable rating scale for monitoring the severity of OMG.
Project description:Background Myasthenia gravis (MG) is an autoimmune disorder with fluctuating muscle weakness, divided into generalized and localized (ocular) forms. Maternal antibodies to acetylcholine receptors cross the placenta and may cause transient neonatal myasthenia gravis (TNMG). We present a case of seronegative maternal ocular MG and delayed TNMG. Case A 29-year-old G3P1011 underwent cesarean birth of a male infant who developed oxygen desaturation requiring supplemental oxygen on day of life (DOL) 3. Based on the clinical course and after exclusion of other diagnoses, the infant was diagnosed with TNMG. Infant's condition improved spontaneously and he was weaned off supplemental oxygen and discharged home on DOL 12. Conclusion Infants born to mothers with seronegative localized (ocular) MG are also susceptible to TNMG which may be late in onset.