Efficacy and safety of rituximab in anti-synthetase antibody positive and negative subjects with idiopathic inflammatory myopathy: a registry-based study

Leclair, Valérie; Galindo-Feria, A. S.; Dastmalchi, Maryam; Holmqvist, Marie; Lundberg, Ingrid E.

doi:10.1093/rheumatology/key450

Cited by 26 publications

(12 citation statements)

References 19 publications

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“…Moreover, in three patients in two reports, mycophenolate mofetil, which has the same mechanism as MZB, was used 22,23) . T cells are thought to play a critical role in myositis-associated ILD 24) , and rituximab, which acts by depleting immunoglobulin-producing CD20 + B cells, has shown benefit for both lung function and radiologic parameters in antisynthetase syndrome 25,26) . Though tacrolimus specifically suppresses the activity of T lymphocytes, MZR suppresses T and B lymphocytes, suggesting that is effective in autoantibody-associated diseases, such as anti-ARS syndrome.…”

Section: Discussionmentioning

confidence: 99%

Mizoribine treatment in an elderly diabetic patient with antisynthetase-associated interstitial lung disease

Nagai¹,

Niisaka²,

Nakajima³

et al. 2020

J Rural Med

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Objective: Immunosuppressive therapy for interstitial lung disease (ILD) is often necessary, but the standard regimen for antisynthetase-associated ILD has not been established. Patient: An 80-year-old man was hospitalized for severely progressive dyspnea. Bilateral interstitial shadows occurred 1 month before the event. Serological findings showed that he had antisynthetase-associated ILD, as identified by strong positivity for antiaminoacyl-transfer RNA synthetase (ARS) antibody, despite no evidence of myositis. He was treated transiently with noninvasive positive pressure ventilation and steroid-pulse therapy followed by 60 mg/day of oral prednisolone. However, his diabetes mellitus was aggravated by corticosteroid therapy; thus, a combination of low-dose steroid and mizoribine (MZB), which has a low risk of aggravating glucose intolerance, was used. Results: The patient's clinical symptoms and daily life activities have been well persevered as an outpatient and well maintained with 200 mg of MZB and 10 mg of prednisolone for several months without obvious clinical recurrence and without any remarkable steroid-and MZB-related side effects. Conclusion: The use of MZB appeared to suppress the pathophysiology of anti-ARS antibody-associated ILD.

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Section: Discussionmentioning

confidence: 99%

Mizoribine treatment in an elderly diabetic patient with antisynthetase-associated interstitial lung disease

Nagai¹,

Niisaka²,

Nakajima³

et al. 2020

J Rural Med

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“…The clinical relevance of the respective autoantibody during rituximab treatment was assessed in a registry-based study with 43 myositis patients, which showed that the majority of both antisynthetase antibody (ARS-ab)–positive and ARS-ab-negative patients had moderate or major improvements, but only the ARS-ab-positive group experienced a significant steroid-sparing effect [ 43 ].…”

Section: Antibody Therapies In Dm Pm Ass Om and Nmmentioning

confidence: 99%

“…A risk of serious infections, including pneumonia, urosepsis and herpes zoster, was noted in the RIM trial in which 26 serious adverse events were related to the drug amongst the 195 participants completing the trial [ 27 ]. In the register-based study by Leclair et al three deaths resulting from severe pneumonia were reported [ 43 ]. Although rituximab is generally safe and effective in treating myositis, close treatment monitoring is necessary and patient´s comorbidities and individual risk factors need to be taken into account.…”

Section: Antibody Therapies In Dm Pm Ass Om and Nmmentioning

confidence: 99%

Antibody Therapies in Autoimmune Inflammatory Myopathies: Promising Treatment Options

2022

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Inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), antisynthetase syndrome (ASS) and overlap myositis (OM), in short myositis, are rare diseases. All forms of myositis have progressive muscle weakness in common, with each subtype characterized by different autoantibody profiles, histological findings and extramuscular manifestations. Due to better understanding of the pathogenesis of the muscle inflammation in myositis, new molecular pathways for targeted therapy have been discovered. Current therapies aim at different components of the innate or the adaptive immune response. Additionally, non-inflammatory mechanisms in myositis have come into focus as possible treatment targets. The use of therapeutical antibodies in myositis has been examined in various clinical studies, several of them randomized controlled ones: Depletion of B-cells by rituximab has been established as treatment of refractory myositis. IVIG, an antibody therapy in the wider sense, has now been licensed for DM following a recent positive clinical trial. Negative study results were reported in randomized trials with infliximab, sifalimumab and bimagrumab. Studies on basiliximab and eculizumab are currently underway, and are expected to yield results in a couple of years. Despite some promising results of clinical studies with antibody therapy in myositis, further research is crucial to optimize the treatment for this debilitating disease and to find treatment alternatives for treatment-refractory patients.

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“…Letztere unterscheiden sich von antigenspezifischen B-Zellen, die in sehr geringer Häufigkeit im peripheren Blut vorhanden sind. Eine entscheidende Rolle der B-Zellen bei der Pathogenese der IIM wird durch die relative Wirksamkeit von B-Zell-gerichteten Therapien wie Rituximab bei der Behandlung der IIM [65-67], der endomysialen Produktion des B-Zell-aktivierenden Faktors (BAFF), dem Vorhandensein von B-Zellen und Plasmazellen im Muskelgewebe, der Antikörperproduktion und der endomysialen B-Zell-Reifung zum Teil im Muskel selbst belegt [68, 69].…”

Section: Humorale Immunität Bei Dm Und Imnm: Die Rolle Der B-zellen U...unclassified

Pathophysiologische Mechanismen und Behandlung von Dermatomyositis und immunvermittelten nekrotisierenden Myopathien: Ein fokussiertes Review

et al. 2022

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Idiopathische entzündliche Myopathien (IIM), allgemein als Myositis bekannt, sind eine gemischte Gruppe von seltenen Autoimmunerkrankungen, die hauptsächlich Skelettmuskeln betreffen, obwohl auch andere Organe oder Gewebe beteiligt sein können. Das wichtigste klinische Merkmal der Myositis ist eine subakute, fortschreitende, symmetrische Muskelschwäche in den proximalen Armen und Beinen, während Subtypen der Myositis auch außermuskuläre Merkmale wie Hautbeteiligung, Arthritis oder interstitielle Lungenerkrankung (ILD) aufweisen können. Zu den etablierten Untergruppen der IIM gehören die Dermatomyositis (DM), die immunvermittelte nekrotisierende Myopathie (IMNM), das Antisynthetase-Syndrom (ASyS), die Myositis bei Overlap-Syndrom (OM) und die Einschlusskörpermyositis (IBM). Obwohl sich die klinischen Merkmale dieser Untergruppen überschneiden, deuten die großen Unterschiede in den klinischen Manifestationen der IIM auf unterschiedliche pathophysiologische Mechanismen hin. Es ist bekannt, dass verschiedene Komponenten des Immunsystems bei der IIM eine wichtige Rolle spielen, obwohl die genauen pathophysiologischen Mechanismen, die zu den Muskelschäden führen, noch unbekannt sind. Die derzeitige Behandlung, die aus Glukokortikoiden und anderen immunsuppressiven oder immunmodulierenden Wirkstoffen besteht, führt häufig nicht zu einer anhaltenden positiven Reaktion und ist mit verschiedenen unerwünschten Wirkungen verbunden. Es wurden neue therapeutische Ziele identifiziert, die die Ergebnisse bei Patienten mit IIM verbessern könnten. Ein besseres Verständnis der sich überschneidenden und abweichenden pathophysiologischen Mechanismen der wichtigsten Untergruppen der Myositis ist notwendig, um die Behandlung zu optimieren. Ziel dieser Übersicht ist es, über die jüngsten Fortschritte bei DM und IMNM zu berichten.

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Efficacy and safety of rituximab in anti-synthetase antibody positive and negative subjects with idiopathic inflammatory myopathy: a registry-based study

Cited by 26 publications

References 19 publications

Mizoribine treatment in an elderly diabetic patient with antisynthetase-associated interstitial lung disease

Mizoribine treatment in an elderly diabetic patient with antisynthetase-associated interstitial lung disease

Antibody Therapies in Autoimmune Inflammatory Myopathies: Promising Treatment Options

Pathophysiologische Mechanismen und Behandlung von Dermatomyositis und immunvermittelten nekrotisierenden Myopathien: Ein fokussiertes Review

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