Twenty-seven cases of drug-induced interstitial lung disease associated with imatinib mesylate

Ohnishi, Kazunori; Sakai, Fumikazu; Kudoh, Shouji; Ohno, Ryuzo

doi:10.1038/sj.leu.2404207

Cited by 90 publications

(98 citation statements)

References 7 publications

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“…Side effects such as edema, myalgias, nausea, vomiting, anemia, leukopenia, thrombocytopenia, or increased levels of liver transaminases did not occur. There were also no signs of cardiomyopathy noted on echocardiograms and no signs of imatinib mesylate-induced pneumonitis (12,13).…”

Section: Case Reportmentioning

confidence: 98%

Treatment of pulmonary fibrosis for twenty weeks with imatinib mesylate in a patient with mixed connective tissue disease

Distler¹,

Manger²,

Spriewald³

et al. 2008

Arthritis & Rheumatism

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Interstitial lung disease, which is common in patients with mixed connective tissue disease (MCTD), can progress to severe pulmonary fibrosis. The tyrosine kinase inhibitor imatinib mesylate has recently been shown to prevent experimental pulmonary, dermal, and renal fibrosis. Our patient, a 64‐year‐old woman with MCTD and rapidly progressive pulmonary fibrosis, presented with rapid deterioration despite treatment with immunosuppressants. During 20 weeks of treatment with imatinib mesylate at 400 mg/day, our patient improved significantly according to several outcome measures, including New York Heart Association classification, diffusing capacity for carbon monoxide, 6‐minute walking distance, arterial oxygen pressure, and reduction of ground‐glass opacities seen on high‐resolution computed tomography. No adverse effects of imatinib mesylate were observed. These findings suggest that imatinib mesylate might be effective in patients with fibrotic diseases and warrant the initiation of larger clinical studies on the safety and efficacy of imatinib mesylate in connective tissue diseases.

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Section: Case Reportmentioning

confidence: 98%

Treatment of pulmonary fibrosis for twenty weeks with imatinib mesylate in a patient with mixed connective tissue disease

Distler¹,

Manger²,

Spriewald³

et al. 2008

Arthritis & Rheumatism

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“…However, there have been reports of patients with chronic myeloid leukaemia developing interstitial pneumonitis when treated with 400 mg/ day oral imatinib mesylate [43][44][45]. The mechanisms causing these symptoms remain unclear and further studies will reveal whether imatinib mesylate can cause these adverse effects in patients with IPF/UIP and whether it is a potential drug in the treatment of human IPF/UIP.…”

Section: Discussionmentioning

confidence: 99%

Imatinib Mesylate Inhibits Fibrogenesis in Asbestos-Induced Interstitial Pneumonia

Vuorinen

Gao

Oury

et al. 2007

Experimental Lung Research

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Profibrogeneic cytokines contribute to the accumulation of myofibroblasts in the lung interstitium in idiopathic pulmonary fibrosis (IPF). Imatinib mesylate, a tyrosine kinase inhibitor specific for Abl, platelet-derived growth factor receptor (PDGFR) and c-Kit tyrosine kinases, has been shown to inhibit fibrosis and profibrotic signaling in mouse models of inflammation-mediated lung reactions. The authors tested imatinib mesylate in vivo in a mouse model of crocidolite asbestosinduced progressive fibrosis. The ability of imatinib mesylate to inhibit profibrogeneic cytokineinduced human pulmonary fibroblast migration was tested in vitro and the expression of its target protein tyrosine kinases was assessed with immunofluorescence. In vivo, 10 mg/kg/day imatinib mesylate inhibited histological parenchymal fibrosis and led to a decrease in collagen deposition, but had no significant effect on asbestos-induced neutrophilia. However, 50 mg/kg/day imatinib mesylate did not inhibit collagen deposition. In vitro, IPF fibroblasts expressed Abl, PDGFR-α, PDGF-β, but not c-Kit, and 1 μM imatinib mesylate inhibited profibrogeneic cytokine-induced IPF fibroblast migration. These results suggest that imatinib mesylate is a potential and specific inhibitor of fibroblast accumulation in asbestos-induced pulmonary fibrosis. KeywordsAsbestos; imatinib mesylate; platelet-derived growth factor receptor; pulmonary fibrosis Idiopathic pulmonary fibrosis (IPF) (histopathology of usual interstitial pneumonia [UIP]) is a chronic, progressive lung disease with unknown etiology and characterized by fibroproliferation and destruction of the lung parenchyma [1,2]. Treatment has been focused on anti-inflammatory therapies, but due to their poor efficacy, with no effect on patient survival, new therapeutic modalities are being sought. Several novel therapeutic trials derived from animal models have also proven disappointing in the clinical settings. One explanation to the poor adaptability of animal models into clinical practice may be that the widely used mouse bleomycin-or radiation-induced fibrosis models may not mimic human UIP lesions [3], which are progressive and often devoid of inflammatory cells. Imatinib mesylate has not been previously tested in asbestos-induced progressive pulmonary fibrosis of mice, where the histopathology is very similar to human IPF/UIP. Although the antifibrotic mechanism of imatinib mesylate is likely to be the inhibition of PDGF-and transforming growth factor-β (TGF-β)-mediated cell signaling, as shown by Daniels and coworkers [11], the effect of imatinib mesylate on human pulmonary fibroblast migration has not been tested in vitro. The aim of this study was to assess whether imatinib mesylate prevents fibrogenesis in asbestos-induced pulmonary fibrosis of mice and to investigate imatinib mesylate inhibition of human pulmonary fibroblast migration as a potential mechanism of its antifibrotic effects. Primary human IPF fibroblasts expressed the protein tyrosine kinases targeted by imatinib mesylate ...

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“…Dear Editor, Several cases of drug-induced pneumonitis in patients treated with imatinib have been reported to date [1]. Here, we report acute drug-induced pneumonitis necessitating therapy discontinuation in a 54-year-old man with primary myelofibrosis (PMF) treated with imatinib.…”

mentioning

confidence: 93%

Imatinib, cytokines and interstitial lung disease in a patient with primary myelofibrosis

Robibaro¹,

Kropfmueller²,

Prokop³

et al. 2009

Ann Hematol

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Twenty-seven cases of drug-induced interstitial lung disease associated with imatinib mesylate

Cited by 90 publications

References 7 publications

Treatment of pulmonary fibrosis for twenty weeks with imatinib mesylate in a patient with mixed connective tissue disease

Treatment of pulmonary fibrosis for twenty weeks with imatinib mesylate in a patient with mixed connective tissue disease

Imatinib Mesylate Inhibits Fibrogenesis in Asbestos-Induced Interstitial Pneumonia

Imatinib, cytokines and interstitial lung disease in a patient with primary myelofibrosis

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