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. 2024 Dec 23:15:1502721.
doi: 10.3389/fimmu.2024.1502721. eCollection 2024.

Cutoffs on severity metrics for minimal manifestations or better status in patients with generalized myasthenia gravis

Genya Watanabe  1 , Yoshiki Takai  2 , Yuriko Nagane  3 , Tomoya Kubota  4 , Manato Yasuda  5 , Hiroyuki Akamine  5 , Yosuke Onishi  5 , Akiyuki Uzawa  5 , Naoki Kawaguchi  6 , Masayuki Masuda  7 , Shingo Konno  8 , Itaru Amino  9 , Naoya Minami  9 , Takashi Kimura  10 , Makoto Samukawa  11 , Takamichi Sugimoto  12 , Yasushi Suzuki  1 , Masanori P Takahashi  4 , Shigeaki Suzuki  13 , Hiroyuki Murai  14 , Masashi Aoki  2 , Kimiaki Utsugisawa  3
Affiliations

Cutoffs on severity metrics for minimal manifestations or better status in patients with generalized myasthenia gravis

Genya Watanabe et al. Front Immunol. .

Abstract

International consensus guidance and Japanese clinical guidelines for myasthenia gravis (MG) recommend achieving minimal manifestations or better status (MM-or-better) as the severity component of the treatment goal. However, the subjective nature of determining MM can result in ambiguity regarding this category in clinical practice and clinical trials. This study analyzed severity metrics in a large number of MG patients to propose criteria for MM-or-better. We utilized data obtained from 3800 MG patients who participated in nationwide cross-sectional surveys in Japan. Among these, 2784 patients with generalized MG were divided into two groups based on MG Foundation of America postintervention status: MM-or-better status (n = 1432); and improved-or-worse (I-or-worse) status (n = 1352). We compared severity metrics (MG-activities of daily living scale [MG-ADL], quantitative MG score [QMG], and MG composite scale [MGC]) between groups and calculated cutoff values to separate the two groups. Using these cutoffs, patients subjectively assigned as MM-or-better were classified into strict MM-or-better (below a cutoff) or optimistic MM-or-better (above a cutoff) groups, and clinical characteristics were then compared. Cutoff values for strict MM-or-better were MG-ADL ≤2, QMG ≤7, and MGC ≤4 (sensitivity 82.0%, 88.7%, and 87.4%; specificity 85.0%, 70.0%, and 77.9%; and accuracy 91.2%, 88.7%, and 90.7%, respectively). Mean values of the revised 15-item MG quality of life scale were significantly lower in the strict MM-or-better group than in the optimistic MM-or-better group. Quantitative criteria for MM-or-better appear likely to be useful in the context of rigorous clinical trials and also as reference information in clinical settings.

Keywords: cutoff value; minimal manifestations; myasthenia gravis; myasthenia gravis foundation of America postintervention status; receiver operating characteristic curve; treatment goal.

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Conflict of interest statement

GW has received honoraria for lectures from Argenx. YN has received speaker honoraria from Argenx, Alexion Pharmaceuticals, Japan Blood Products Organization, Takeda Pharmaceutical Company Limited and UCB. TK reports honoraria for lectures from Argenx, Alexion Pharmaceuticals and UCB Pharma. AU has received honoraria from Alexion Pharmaceuticals, UCB, and Argenx. MM has served as a paid consultant for UCB Pharma and Alexion Pharmaceuticals, and has received speaker honoraria from Alexion Pharmaceuticals, Argenx Japan, UCB Japan, Asahi Kasei Pharma, Takeda Pharmaceutical, Japan Blood Products Organization and Chugai Pharmaceutical Co., Ltd. NM has received honoraria from Argenx. MT reports unrestricted research grants from Japan Blood Products Organization and Astellas Pharma outside the submitted work, and has served as a paid consultant for Alexion, Argenx, Hanall BioPharma, and UCB Pharma and received honoraria for lectures from Argenx, Alexion Pharmaceuticals, and UCB Pharma. SS has received personal fees from Alexion Pharmaceuticals, Argenx, and UCB Pharma, the Japan Blood Products Organization, and Asahi Kasei Medical. HM has served as a paid consultant for Alexion, Argenx, UCB Pharma and Roche, and has received speaker honoraria from the Japan Blood Products Organization and Chugai Pharmaceutical. KU has served as a paid consultant for UCB Pharma, Argenx, Janssen Pharma, Viela Bio, Chugai Pharma, Hanall BioPharma, Merck and Mitsubishi Tanabe Pharma, and has received speaker honoraria from Argenx, Alexion Pharmaceuticals, UCB Pharma and the Japan Blood Products Organization. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
CONSORT diagram of study participants; I, improved status; MM, minimal manifestations; MG, myasthenia gravis.
Figure 2
Figure 2
ROC curve described with data of MG-ADL (n = 2784) (A), QMG (n = 1473) (B), MGC (n = 2784) (C), and cMG-QOL15 (n = 2784) (D). Vertical axis shows sensitivity (true positive); horizontal axis shows 1-specificity (false positive). Cutoff points correspond to the point on the ROC curve where sensitivity - (1 - specificity) is maximal; cMG-QOL15, corrected 15-item myasthenia gravis quality of life scale; MG-ADL, myasthenia gravis activities of daily living scale; MGC, myasthenia gravis composite scale; QMG, quantitative myasthenia gravis score; ROC, receiver operating characteristic.
Figure 3
Figure 3
Comparison of Strict and Optimistic MM-or-better with cutoffs on MG-ADL, QMG, and MGC regarding corrected 15-items myasthenia gravis quality of life scale (cMG-QOL15). MG-ADL, myasthenia gravis activities of daily living scale; MGC, myasthenia gravis composite scale; MM, minimal manifestations; QMG, quantitative myasthenia gravis score; Mann–Whitney U-test; *p <.0001.
See this image and copyright information in PMC

References

    1. Sanders DB, Evoli A. Immunosuppressive therapies in myasthenia gravis. Autoimmunity. (2010) 43:428–35. doi: 10.3109/08916930903518107 - DOI - PubMed
    1. Gilhus NE. Autoimmune myasthenia gravis. Expert Rev Neurother. (2009) 9:351–58. doi: 10.1586/14737175.9.3.351 - DOI - PubMed
    1. Masuda M, Utsugisawa K, Suzuki S, Nagane Y, Kabasawa C, Suzuki Y, et al. . The MG-QOL15 Japanese version: validation and associations with clinical factors. Muscle Nerve. (2012) 46:166–73. doi: 10.1002/mus.23398 - DOI - PubMed
    1. Suzuki S, Masuda M, Uzawa A, Nagane Y, Konno S, Suzuki Y, et al. . Japan MG registry: Chronological surveys over 10 years. Clin Exp Neuroimmunol. (2023) 14:5–12. doi: 10.1111./cen3.12731 - DOI
    1. Utsugisawa K, Suzuki S, Nagane Y, Masuda M, Murai H, Imai T, et al. . Health-related quality of life and treatment targets in myasthenia gravis. Muscle Nerve. (2014) 50:493–500. doi: 10.1002/mus.24213 - DOI - PubMed

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