Outcome Measures in Clinical Trials of Patients With Myasthenia Gravis

Abstract

Myasthenia gravis (MG) is a heterogeneous disorder whose clinical presentation ranges from mild ocular deficits to severe widespread weakness. This variance poses a challenge when quantifying clinical deficits. Deficits and symptoms are quantified using standardized clinical scales and questionnaires which are often used as outcome measures. The past decades have seen the development of several validated outcome measures in MG, which are used in clinical trials to obtain regulatory approval. In recent years, emphasis has moved from objective assessments to patient-reported outcomes. Despite a growing body of literature on the validity of the MG-specific outcome measures, several unresolved factors remain. As several novel therapeutics are currently in clinical development, knowledge about capabilities and limitations of outcome measures is needed. In the present paper, we describe the most widely used clinical classifications and scales in MG. We highlight the choice of outcome measures in published and ongoing trials, and we denote whether trial efficacy was reached on these outcomes. We discuss advantages and limitations of the individual scales, and discuss some of the unresolved factors relating to outcome assessments in MG.

Digital Biomarkers for Neuromuscular Disorders: A Systematic Scoping Review

“…Only one article was an animal study, and four out of the nine studies were conducted on ALS patients. Among diseases belonging to NMDs, ALS is one of few diseases for which a functional rating scale (ALSFRS-R) has been recognized as a gold-standard outcome measure that has been widely used in clinical practice and research [ 23 ]. One of the four studies for ALS suggested that the marker obtained through the digital sensor had a good correlation with the ALSFRS-R score [ 14 ]; another study, which assessed speech features of ALS patients, stated that the biomarkers obtained from the mobile application could detect earlier disease progression than ALSFRS-R bulbar score [ 15 ].…”

Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease

“…gMG is characterised by fluctuating and variable muscle weakness, muscle fatigability (i.e., triggering or worsening of an impairment with usual or normal activities, or onset/worsening of an impairment over the course of the day) and generalised fatigue (i.e., becoming increasingly tired). Symptoms contribute differently to the degree of clinical disability [ 12 ] but collectively impact many aspects of the quality of life of people living with MG. These range from physical exertions (e.g., walking and doing housework), social activities, sleep, psychological health and professional development [ 13 – 15 ].…”

“…Due to this fluctuating and unpredictable disease course and the subjective nature of symptoms such as fatigue, PRO instruments have the potential to provide greater insight into the experience of people living with MG than traditional clinical endpoints, and regulators are encouraging their use as primary efficacy trial endpoints [ 12 ]. However, the heterogeneity of the disease can lead to a lack of correlation between some clinical measures at onset and remission or worsening episodes (e.g., the Myasthenia Gravis Foundation of America [MGFA] clinical classification) [ 16 ].…”

“…Multiple PRO instruments have been developed to capture the impact of MG on an individual’s life, including the Myasthenia Gravis Activities of Daily Living (MG-ADL) [ 19 ], MG Disability Assessment (MG-DIS) [ 14 ], the MG Fatigue Scale (MGFS) [ 20 ], and the MG Quality of Life 15 (MG-QoL-15) [ 21 ]. However, these PRO instruments may not comprehensively assess the range of symptoms and functional impact proximal to the MG experience [ 12 ] and fatigability, in particular, is often overlooked [ 22 ]. Additionally, these PRO instruments largely fail to meet the latest regulatory and expert recommendations in relation to having patients involved in the development process [ 4 , 23 , 24 ].…”

Development of a Computerized Adaptive Test for Quantifying Chinese Medicine Syndrome of Myasthenia Gravis on Basis of Multidimensional Item Response Theory

“…Restrictive respiratory failure caused by severe weakness of respiratory muscle could even lead to emergency known as MG crisis in 15% of MG patients [2]. e heterogeneity of clinical appearances of MG ranging from mild ocular deficits to severe widespread weakness posed a challenge for clinical assessment of MG patients [3]. Moreover, multiple comorbidities among patients with chronic disease were also commonly reported which made it difficult for the management of MG. Due to the disease heterogeneity, MG is increasingly acknowledged as a syndrome more than a single disease [4].…”