Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Nataraju, Aravinda Settikere; Raja, Shiva Kumar Bangalore; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

doi:10.3205/000239

Cited by 16 publications

(8 citation statements)

References 47 publications

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“…Therefore, Across all criteria there were a higher proportion of women, MuSK antibody positivity, and longer mean disease duration in refractory patients (Table 2). This trend has been reported in various other refractory MG studies [4,5,15]. Interestingly, neither the ICG or REGAIN criteria resulted in patients with pure ocular disease classified as refractory.…”

Section: Discussionsupporting

confidence: 72%

“…In this cohort of individuals with MG, we found a wide variability in the proportion of refractory cases according to the definition used. Previous literature has reported a prevalence of refractory MG between 10%-20% of the general MG population [3][4][5][6][7]. In this cohort we found rates beyond those numbers (i.e., less than 10% and up to 40%), this is not surprising considering the differences between criteria.…”

Section: Discussionsupporting

confidence: 64%

“…management, there remains a number of patients who are refractory to treatment, and this proportion varies in the literature from 10% to 20% [3][4][5][6][7].…”

mentioning

confidence: 99%

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Performance of different criteria for refractory myasthenia gravis

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Biswas

Mendoza

et al. 2020

Euro J of Neurology

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Background and purpose Defining refractory myasthenia gravis is important, as this can drive clinical decision making, for example, by escalating treatments in refractory individuals. There are several definitions of refractory myasthenia, and their performances have not been compared. Having valid and reliable criteria can help select patients in whom more aggressive treatments may be needed. Methods We applied five different refractory myasthenia criteria (Drachman, Mantegazza, Suh, the International Consensus Guideline (ICG), and the randomised controlled trial of eculizumab in refractory, anti‐acetylcholine receptor positive, generalised myasthenia gravis (REGAIN), to a cohort of 237 patients. We compared the proportion of refractory patients among different criteria and their scores on disease severity, fatigue, and quality‐of‐life (QoL) scales. We also assessed the agreement for each criterion between two trained assessors. Results The Drachman, Mantegazza, and Suh criteria resulted in high proportions of refractory individuals (40.1%, 39.2%, and 38.8%, respectively), compared with the ICG and REGAIN criteria (9.7% and 3.0%, respectively). Refractory patients by the ICG and REGAIN criteria had worse disease severity, QoL, and fatigue scores, compared with patients classified as refractory by other criteria. All criteria had high agreement between raters (between 70% and 100%). Conclusions There is high variability in the proportion of refractory myasthenia gravis patients depending on the criteria used, with ICG and REGAIN criteria capturing patients with worse disease severity. This reflects conceptual differences as to what refractory means. Further multicenter studies are needed to determine appropriate criteria for refractory myasthenia gravis.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionsupporting

confidence: 64%

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Performance of different criteria for refractory myasthenia gravis

Tran

Biswas

Mendoza

et al. 2020

Euro J of Neurology

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“…Previous articles report a lower percent of double seronegativity among refractory MG patients that ranges from 0% to 21%. [2][3][4] However, in accordance with our findings, Rath et al 4 reported that 33.3% of DSNMG and 9.1% of AChR-positive patients developed refractory MG; our percentages were 27.3% and 11.4%, respectively. Not surprisingly, antibodies against LRP4 were not present in any of the DSNMG refractory patients, because LRP4-positive patients tend to respond well to standard MG therapy.…”

Section: Discussionsupporting

confidence: 90%

“…The studies suggested that females and those with a younger age at onset, muscle-specific tyrosine kinase (MuSK) antibodies, and thymoma have more severe disease that tends to be more resistant to treatment. [2][3][4] The aim of this study was to describe the autoantibody profile, clinical features, and treatment responsiveness of MG patients with a refractory phase.…”

Section: Introductionmentioning

confidence: 99%

Autoantibody profile in myasthenia gravis patients with a refractory phase

Veltsista

Kefalopoulou

Tzartos³

et al. 2022

Muscle and Nerve

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Introduction/Aims: A subgroup of myasthenia gravis (MG) patients fail to respond adequately to recommended treatments, a condition referred to as refractory MG. During the refractory phase, patients experience persistent debilitating symptoms with potential life-threatening events or inability to reduce immunosuppressant dosages and minimize long-term toxicities.Methods: We conducted a retrospective, single-center study of 113 MG patients to investigate the autoantibody profile and clinical characteristics of refractory MG patients, compared with nonrefractory patients, based on predefined criteria.Results: Fifteen patients (13.3%) were classified as refractory. Double-seronegative MG (DSNMG), without detectable nicotinic acetylcholine receptor (AChR) or musclespecific tyrosine kinase (MuSK) antibodies, was identified in six refractory patients, significantly higher than those with nonrefractory MG (40% vs 16.3%; P = .031).None of the refractory patients had MuSK antibodies. Patients in the refractory group more frequently had an earlier disease onset, thymic pathology, and thymectomy (P ≤. 03 for all).

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How should newer therapeutic agents be incorporated into the treatment of patients with myasthenia gravis?

Gwathmey,

Ding,

Hehir

et al. 2024

Muscle and Nerve

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Generalized myasthenia gravis (gMG) is a postsynaptic neuromuscular junction disorder that results in fatigable muscle weakness. The traditional treatment approach includes the use of acetylcholinesterase inhibitors, corticosteroids, and steroid‐sparing immunosuppressant therapies (ISTs) for chronic management, whereas exacerbations and crises are managed with intravenous immunoglobulin (IVIg) and plasma exchange (PLEX). Over the past 6 years, four new therapeutic agents with novel immunological mechanisms of action—complement and neonatal Fc receptor (FcRn) inhibition—were approved as a result of clinically significant improvement in gMG symptoms of those treated with these newer agents in Phase 3 clinical trials. At present, it is unclear when and in whom to initiate these therapeutic agents and how to integrate them into the current treatment paradigm. When selecting a newer therapeutic agent, we use a simple equation: Value = Clinical Improvement/(Cost + Side Effects + Treatment Burden), which guides our decision‐making. We consider using these novel therapeutic agents in two specific clinical situations. Firstly, the newer agents are fast‐acting, suggesting they can be used in clinically unstable patients as “bridge therapy,” and secondly, they provide additional options for those patients considered treatment‐refractory. There are downsides, however, including treatment cost, unique side effect profiles, and intravenous and subcutaneous drug administration (though for some, this may be an advantage). As additional drugs enter the marketplace with unique mechanisms of action, routes of administration, and dosing schedules, the placement of the novel therapeutic agents in the gMG treatment algorithm will likely evolve.

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Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

Cited by 16 publications

References 47 publications

Performance of different criteria for refractory myasthenia gravis

Performance of different criteria for refractory myasthenia gravis

Autoantibody profile in myasthenia gravis patients with a refractory phase

How should newer therapeutic agents be incorporated into the treatment of patients with myasthenia gravis?

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