Immune checkpoint inhibitors in the onset of myasthenia gravis with hyper<scp>CK</scp>emia

Takamatsu, Koutaro; Nakane, Shunya; Suzuki, Shigeaki; Kosaka, Takayuki; Fukushima, Satoshi; Kimura, Toshihiro; Miyashita, Azusa; Mukaino, Akihiro; Yamakawa, Shiori; Watanabe, Keisuke; Jinnin, Masatoshi; Komohara, Yoshihiro; Ihn, Hironobu; Ando, Yumiko

doi:10.1002/acn3.654

Cited by 34 publications

(27 citation statements)

References 42 publications

(42 reference statements)

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“…It is known that anti‐titin antibody is accompanied with myositis . Moreover, myasthenia gravis with hyperCKemia is suspected to have a more complicated prognosis than in myasthenia gravis without hyperCKemia; thus, before ICI treatment, AChR antibodies and anti‐striational antibodies should be measured if available . There is a possibility that patients already have subclinical myasthenia gravis, and ICIs are considered the triggering factors of flare‐up, but more studies are needed to confirm this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Myasthenia gravis and myopathy after nivolumab treatment for non‐small cell lung carcinoma: A case report

et al. 2019

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Here, we report a case of myasthenia gravis and myopathy in a patient treated with nivolumab. A 76‐year‐old man who had been treated with four doses of nivolumab because of non‐small cell lung cancer (NSCLC) presented with proximal‐dominant muscle weakness and fluctuating ptosis and diplopia. Serologic studies revealed increased levels of muscle enzymes including creatine phosphokinase (2934 U/L), and acetylcholine receptor antibody was positive (1.31 nmol/L). Following electrodiagnostic study, he was diagnosed with myasthenia gravis and active stage of myopathy. After discontinuation of nivolumab, he was treated with corticosteroids, intravenous immunoglobulin G, and pyridostigmine. The neuromuscular symptoms and serologic abnormalities of the patient markedly improved. Currently, he is taking oral steroids and pyridostigmine without further immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Myasthenia gravis and myopathy after nivolumab treatment for non‐small cell lung carcinoma: A case report

et al. 2019

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“…39 StrAbs are regarded as possible biomarkers of irAEs, and it is recommended that they be evaluated in the guidelines published by the American Society of Clinical Oncology. 42,43 F I G U R E 1 A 65-year-old man with non-small cell lung cancer was treated with nivolumab monotherapy, and developed myasthenia gravis and myocarditis. (a) A cardiac muscle biopsy showed lymphocyte infiltration of the myocardium with much greater infiltration of CD8 + T cell lymphocytes than CD4 + T cells.…”

Section: Immune-rel Ated Adver S E E Ventsmentioning

confidence: 99%

Anti‐striational antibodies: Expanding their clinical significance

Suzuki

Nagane

Uzawa

et al. 2020

Clinical & Exp Neuroim

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Myasthenia gravis (MG) is an organ-specific autoimmune disorder generally mediated by anti-acetylcholine receptor (AChR) or, less frequently, by anti-muscle-specific tyrosine antibodies at the neuromuscular junction. 1 In the 1970s, before the discovery of anti-AChR antibodies, anti-striational antibodies (StrAbs) were known as serum immunoglobulins that react with cross-striations of skeletal muscle in MG patients. Indirect immunofluorescence of animal skeletal muscle tissue was the original method for detecting StrAbs. 2 StrAbs had been expected to be useful as biomarkers of MG; however, immunoreactivity on indirect immunofluorescence was also observed in other disorders and in normal controls. Because of the low specificity of StrAbs as biomarkers, the diagnostic utility of StrAbs had been regarded to be limited. In the 1990s, several molecules on skeletal and heart muscle proteins were identified as autoantigens of StrAbs. In particular, the

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“…There are several previous reports of pembrolizumab-associated MG with myopathy. [6][7][8] Takamatsu et al 9 reported 17 cases of MG with hyperCKemia associated with ICIs. In most cases, respiratory failure or worsening of MG symptoms was noted immediately after MG onset, while death occurred in some cases.…”

Section: Jcnmentioning

confidence: 99%

Pembrolizumab-Induced Myasthenic Crisis with HyperCKemia in a Patient with Thymoma

et al. 2020

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Immune checkpoint inhibitors (ICIs) mark a new era for cancer treatment, since they act against immune checkpoint proteins and increase antitumor immunity. 1 Despite their efficacy against several cancers, immune-related adverse events (IRAEs) can occur as complications. Neurological complications of ICIs are rare, but they have diverse clinical manifestations. 2 Myasthenia gravis (MG) is a neurological complication of ICIs. 3 Here we report a patient who developed severe MG with hyperCKemia after receiving pembrolizumab therapy for thymoma. A 49-year-old woman was admitted with a 4-day history of general weakness, dyspnea, and dysphagia. Three days prior to the presentation she had received the second course of pembrolizumab (200 mg) for a thymoma with multiple metastases. She had no history of a neuromuscular disorder or similar complaints. Neurological examinations revealed right ptosis without ophthalmoplegia, severe dysarthria with hypophonia, and dysphagia. Weakness of the neck and proximal-dominant upper and lower extremity was noted. The Tensilon test was negative. Laboratory tests revealed marked elevation of serum creatine kinase (CK) (8,362 IU/l). One week later the patient tested positive for the anti-acetylcholine-receptor antibody (6.60 nmol/L). The patient developed labored breathing on day 5 of hospitalization, which worsened and was associated with marked hypercapnia. She was transferred to the intensive care unit, and mechanical ventilation was initiated. She received a high dose of a corticosteroid (1,000 mg/ day methylprednisolone for 5 days) and subsequently received intravenous immunoglobulin (0.4 g/kg/day for 5 days). Her CK level normalized and the weakness in the extremities improved; however, her other symptoms did not improve, and she still required mechanical ventilation. She underwent seven cycles of plasmapheresis on alternate days. She recovered gradually and was weaned off ventilation. She was discharged after 12 weeks of hospitalization without complications. Pembrolizumab is a humanized monoclonal antibody targeting the programmed cell death 1 (PD-1) receptor and acts as a competitive inhibitor to PD-1 receptor binding ligands. 2 The pathomechanism of IRAEs caused by PD-1 inhibitors has not been fully elucidated. IRAEs could be related to increased T-cell activity and autoantibody and inflammatory cytokine levels. MG is an autoimmune disease involving multifaceted autoimmune processes including pathogenetic T-helper 17 cells, regulatory T cells, and proinflammatory cytokines, 4 and so MG may develop as an IRAE. Neurological complications have been reported in approximately 3% of patients receiving PD-1 inhibitor therapy, with the most common being neuromuscular complications including MG, myopathy/myositis, and peripheral neuropathy. 2 Since thymoma may be associated with MG, we were unable to clearly distinguish whether subclinical MG was exacerbated on pembrolizumab administration, caused by pembrolizum

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Immune checkpoint inhibitors in the onset of myasthenia gravis with hyperCKemia

Cited by 34 publications

References 42 publications

Myasthenia gravis and myopathy after nivolumab treatment for non‐small cell lung carcinoma: A case report

Myasthenia gravis and myopathy after nivolumab treatment for non‐small cell lung carcinoma: A case report

Anti‐striational antibodies: Expanding their clinical significance

Pembrolizumab-Induced Myasthenic Crisis with HyperCKemia in a Patient with Thymoma

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