Early fast‐acting treatment strategy against generalized myasthenia gravis

Utsugisawa, Kimiaki; Nagane, Yuriko; Akaishi, Tetsuya; Suzuki, Yasushi; Imai, Tomihiro; Tsuda, Etsuko; Minami, Naoya; Uzawa, Akiyuki; Kawaguchi, Naoki; Masuda, Masayuki; Konno, Shingo; Suzuki, Hidekazu; Murai, Hiroyuki; Akiyama, Masashi

doi:10.1002/mus.25397

Cited by 52 publications

(45 citation statements)

References 16 publications

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“…The Japanese guidelines for MG treatment were updated in 2014 to emphasize the importance of patients' quality of life [24][25][26]. These changes were informed by a large retrospective analysis of Japanese patients with MG that evaluated factors impacting on quality of life, and recommended using early, fast-acting treatment strategies [27]. Such treatment strategies have demonstrated improved outcomes for Japanese patients compared with other approaches using conventional therapies; however, these strategies are not effective for all patients [27], suggesting that new, innovative treatment approaches would be of benefit in these patients.…”

Section: Discussionmentioning

confidence: 99%

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

Murai

Uzawa

Suzuki

et al. 2019

Journal of the Neurological Sciences

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The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with openlabel eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (−2.4 [1.34] and − 3.3 [0.65]); Quantitative Myasthenia Gravis (−2.9 [1.98] and − 4.3 [0.79]); Myasthenia Gravis Composite (−4.5 [2.63] and − 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (−8.6 [5.68] and − 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population.

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Section: Discussionmentioning

confidence: 99%

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

Murai

Uzawa

Suzuki

et al. 2019

Journal of the Neurological Sciences

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“…A recent study found that patients treated with the EFT strategy achieved MM‐5 mg for ≥6 months more frequently and earlier than patients not receiving EFT (Fig. ) . Multivariate Cox regression analysis calculated a hazard ratio of 1.98 ( P < 0.0001) for achieving MM‐5 mg with utilization of EFT.…”

Section: Early Fast‐acting Treatment Strategymentioning

confidence: 93%

Rationale for the clinical guidelines for myasthenia gravis in Japan

Murai

Utsugisawa

Nagane

et al. 2018

Annals of the New York Academy of Sciences

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According to the 2014 Japanese clinical guidelines for myasthenia gravis, the most important priority in treatment is maintaining patients’ health‐related quality of life. Therefore, the initial treatment goal is defined as maintaining a postintervention status of minimal manifestations or better (according to the Myasthenia Gravis Foundation of America classification) with an oral prednisolone dose of 5 mg/day or less. Every effort should be made to attain this level as rapidly as possible. To achieve this goal, the guidelines recommend minimizing the oral prednisolone dose, starting calcineurin inhibitors early in the course of treatment, using intravenous methylprednisolone infusion judiciously (often combined with plasma exchange/plasmapheresis or intravenous immunoglobulin), and effectively treating patients with an early, fast‐acting treatment strategy. The early, fast‐acting treatment strategy enables more frequent and earlier attainment of the initial goal than other strategies. Thymectomy is considered an option for treating nonthymomatous early‐onset myasthenia gravis in patients with antiacetylcholine receptor antibodies and thymic hyperplasia in the early stages of the disease.

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“…One suggested new strategy for increasing the success rates of MM‐or‐better‐5 mg is early fast‐acting treatment (EFT) using reduced oral corticosteroid dose and early combination with calcineurin inhibitors, then using plasma exchange (PE)/plasmapheresis (PP) and/or intravenous immunoglobulin (IVIg) and/or intravenous methylprednisolone pulse therapy to resolve remaining symptoms quickly . However, Japanese studies also showed a considerable population (40%‐50%) of generalized MG patients who had difficulty controlling disease progression even with the new treatment strategy . These patients failed to respond to adequate doses and durations of conventional immunotherapies and required excessive fast‐acting treatments such as PE/PP and IVIg.…”

Section: Introductionmentioning

confidence: 99%

Why is development of new treatments necessary for myasthenia gravis? Recent advances in clinical trials

Imai

2019

Neurology & Clinical Neurosc

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Despite the availability of an increasing variety of disease‐modifying therapies, the proportion of patients with generalized myasthenia gravis (MG) who achieved the practical treatment goal remained low at approximately 50%‐60% in our latest survey. Therefore, there is a need for further development of new treatment options based on novel mechanisms of action for MG treatment. Eculizumab and ravulizumab are monoclonal antibodies used to prevent complement‐mediated damage at the endplate of neuromuscular junction in MG with acetylcholine receptor (AChR) antibody. Neonatal Fc receptor (FcRn) antibodies including efgartigimod and rozanolixizumab are currently in different stages of clinical trial. The FcRn antibodies would be rational therapeutic agents for decreasing the levels of pathogenic autoantibodies with IgG isotypes, resulting in reduction in muscle‐specific kinase (MuSK) antibody as well as AChR antibody. Rituximab, a CD20+ B‐cell depleting monoclonal antibody, also results in a significant decrease in autoantibody titers in serum. Several studies indicate that rituximab may have the potential to treat MuSK‐MG. Monarsen, an antisense oligonucleotide, may reduce the production of acetylcholinesterase. A phase 2 study showed improvement in quantitative MG scores while on the drug. Several case reports showed the efficacy of autologous hemopoietic stem cell transplantation in patients with severe MG refractory to conventional therapies. This article introduces the new drugs and their latest development and discusses the evidence for thymectomy in relation to the Japanese clinical guidelines for MG.

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Early fast‐acting treatment strategy against generalized myasthenia gravis

Cited by 52 publications

References 16 publications

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

Rationale for the clinical guidelines for myasthenia gravis in Japan

Why is development of new treatments necessary for myasthenia gravis? Recent advances in clinical trials

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