Measuring Overall Severity of Myasthenia Gravis (MG): Evidence for the Added Value of the MG Symptoms PRO

Abstract

Introduction Accurate measurement of myasthenia gravis (MG) severity is required for appropriate clinical monitoring of patients with MG and assessment of the benefit of new treatments in clinical trials. Our objective was to explore how MG severity can be measured and to determine how the newly developed MG Symptoms Patient-Reported Outcome (PRO) instrument complements the available measures of MG severity. Methods The conceptual coverage of the Quantitative MG (QMG), MG Composite (MGC), MG-Activities of Daily Living (MG-ADL), and MG Symptoms PRO was scrutinized against core symptoms of MG: muscle weakness in three muscle groups (ocular, bulbar, and respiratory), muscle weakness fatigability, and physical fatigue. Post hoc analyses of the MG0002 study, a Phase 2a clinical trial of rozanolixizumab in adults with moderate to severe generalized MG, included correlation and Rasch model analyses. Results The qualitative appraisal highlighted that only the MG Symptoms PRO captured physical fatigue. Data from 541 assessments (43 unique patients) were used for the analyses. Correlations ranged between 0.56 and 0.74 for the MG-ADL, QMG, MGC, and MG Symptoms PRO Muscle Weakness Fatigability score, and between 0.20 and 0.71 for the MG Symptoms PRO scores focusing on independent muscle groups. Analyses with the Rasch model estimated a meaningful continuum of severity of MG, including all items, except ocular muscles, from the four instruments. The QMG and MG Symptoms PRO had the broadest coverage of the MG severity continuum. Muscle fatigability and physical fatigue were more characteristic of low severity while bulbar weakness indicated more severe MG. Conclusion The severity of MG can be reflected in a meaningful continuum underpinned by the MG-specific outcome measures. Only ocular muscle manifestations were shown to reflect a possibly different facet of MG severity. With its modular nature and comprehensive content, the MG Symptoms PRO provides complementary information to the outcome measures widely used in MG. Trial Registration ClinicalTrials.gov identifier: NCT03052751. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-023-00464-x.

Impact of Ravulizumab on Patient Outcomes and Quality of Life in Generalized Myasthenia Gravis

“…Besides the MG-ADL, available instruments are the MG-DIS (MG Disability scale), 16 the MGQoL15r (MG Quality of Life 15r), 17 and the recently described MG Symptoms PRO (Patient Reported Outcome), designed to capture symptoms as they are perceived by MG patients over a period of 7 days. 18 The MGQoL15r, derived from the MGQoL60 and its shorter version MGQoL15, was found to have a good internal consistency and construct validity with correlation with QMG and MG-ADL scores. 17 The MGQoL15r is now widely used in clinical trials, but the information available from patients enrolled in clinical studies cannot be considered as a comprehensive picture of the whole population of MG patients, since they are strictly related to the RCT setting and the compound under investigation.…”

“…Besides the MG-ADL, available instruments are the MG-DIS (MG Disability scale), 16 the MGQoL15r (MG Quality of Life 15r), 17 and the recently described MG Symptoms PRO (Patient Reported Outcome), designed to capture symptoms as they are perceived by MG patients over a period of 7 days. 18 …”

Clinical meaningfulness and psychometric robustness of the MG Symptoms PRO scales in clinical trials in adults with myasthenia gravis

“…The score for each scale is calculated only if more than 70% of the items in the scale are completed. The MG Symptoms PRO scales have been shown to be complementary to the commonly used measures of MG severity and, most specifically, to provide accurate information to discriminate between the milder levels of severity that may not be captured well by these other instruments ( 9 ). The MG Symptoms PRO scales have features that make it particularly relevant from a clinical perspective (see Box 1 ).…”

“…It was created using the current best standards ( 6 , 7 ), which emphasize the importance of direct patient input during the development of the instrument. Previous analyses of the MG Symptoms PRO scales demonstrated strong psychometric performance in a sample of 43 participants with generalized MG ( 8 ) and highlighted the instrument’s complementarity with the other widely used measures of MG severity, especially its applicability to the milder severity of MG ( 9 ).…”

Myasthenia gravis: the future is here

“…Generalized weakness can range from highly isolated manifestations, particularly bulbar muscles, to widespread muscle weakness, including respiratory insufficiency producing respiratory failure ( 10 ). Despite resolution of manifest weakness with treatment, many patients complain of general fatigue, as assessed by patient-reported outcome measures ( 11 – 13 ) and patient survey ( 14 ). This symptom suggests an etiology outside neuromuscular transmission compromise, which could be explained by concomitant sleep disturbance, psychological factors, and likely the pathological immune reaction, given the common observation of fatigue in other autoimmune disorders ( 15 ).…”