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Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial
OBJECTIVE: To assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis (dcSSc). METHODS: In this phase IIa, open-label, single-arm clinical trial, 30 patients with dcSSc were treated with imatinib 400 mg daily. Patients were monitored monthly...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BMJ Group
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086082/ https://www.ncbi.nlm.nih.gov/pubmed/21398330 http://dx.doi.org/10.1136/ard.2010.143974 |
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author | Spiera, Robert F Gordon, Jessica K Mersten, Jamie N Magro, Cynthia M Mehta, Mansi Wildman, Horatio F Kloiber, Stacey Kirou, Kyriakos A Lyman, Stephen Crow, Mary K |
author_facet | Spiera, Robert F Gordon, Jessica K Mersten, Jamie N Magro, Cynthia M Mehta, Mansi Wildman, Horatio F Kloiber, Stacey Kirou, Kyriakos A Lyman, Stephen Crow, Mary K |
author_sort | Spiera, Robert F |
collection | PubMed |
description | OBJECTIVE: To assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis (dcSSc). METHODS: In this phase IIa, open-label, single-arm clinical trial, 30 patients with dcSSc were treated with imatinib 400 mg daily. Patients were monitored monthly for safety assessments. Modified Rodnan skin scores (MRSS) were assessed every 3 months. Pulmonary function testing, chest radiography, echocardiography and skin biopsies were performed at baseline and after 12 months of treatment. RESULTS: Twenty-four patients completed 12 months of therapy. 171 adverse events (AE) with possible relation to imatinib were identified; 97.6% were grade 1 or 2. Twenty-four serious AE were identified, two of which were attributed to study medication. MRSS decreased by 6.6 points or 22.4% at 12 months (p=0.001). This change was evident starting at the 6-month time point (Δ=−4.5; p<0.001) and was seen in patients with both early and late-stage disease. Forced vital capacity (FVC) improved by 6.4% predicted (p=0.008), and the diffusion capacity remained stable. The improvement in FVC was significantly greater in patients without interstitial lung disease. Health-related quality of life measures improved or remained stable. Blinded dermatopathological analysis confirmed a significant decrease in skin thickness and improvement in skin morphology. CONCLUSIONS: Treatment with imatinib was tolerated by most patients in this cohort. Although AE were common, most were mild to moderate. In this open-label experience, improvements in skin thickening and FVC were observed. Further investigation of tyrosine kinase inhibition for dcSSc in a double-blind randomised placebo controlled trial is warranted. ClinicalTrials.gov, NCT00555581 |
format | Text |
id | pubmed-3086082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BMJ Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-30860822011-05-10 Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial Spiera, Robert F Gordon, Jessica K Mersten, Jamie N Magro, Cynthia M Mehta, Mansi Wildman, Horatio F Kloiber, Stacey Kirou, Kyriakos A Lyman, Stephen Crow, Mary K Ann Rheum Dis Clinical and Epidemiological Research OBJECTIVE: To assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis (dcSSc). METHODS: In this phase IIa, open-label, single-arm clinical trial, 30 patients with dcSSc were treated with imatinib 400 mg daily. Patients were monitored monthly for safety assessments. Modified Rodnan skin scores (MRSS) were assessed every 3 months. Pulmonary function testing, chest radiography, echocardiography and skin biopsies were performed at baseline and after 12 months of treatment. RESULTS: Twenty-four patients completed 12 months of therapy. 171 adverse events (AE) with possible relation to imatinib were identified; 97.6% were grade 1 or 2. Twenty-four serious AE were identified, two of which were attributed to study medication. MRSS decreased by 6.6 points or 22.4% at 12 months (p=0.001). This change was evident starting at the 6-month time point (Δ=−4.5; p<0.001) and was seen in patients with both early and late-stage disease. Forced vital capacity (FVC) improved by 6.4% predicted (p=0.008), and the diffusion capacity remained stable. The improvement in FVC was significantly greater in patients without interstitial lung disease. Health-related quality of life measures improved or remained stable. Blinded dermatopathological analysis confirmed a significant decrease in skin thickness and improvement in skin morphology. CONCLUSIONS: Treatment with imatinib was tolerated by most patients in this cohort. Although AE were common, most were mild to moderate. In this open-label experience, improvements in skin thickening and FVC were observed. Further investigation of tyrosine kinase inhibition for dcSSc in a double-blind randomised placebo controlled trial is warranted. ClinicalTrials.gov, NCT00555581 BMJ Group 2011-03-11 /pmc/articles/PMC3086082/ /pubmed/21398330 http://dx.doi.org/10.1136/ard.2010.143974 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode. |
spellingShingle | Clinical and Epidemiological Research Spiera, Robert F Gordon, Jessica K Mersten, Jamie N Magro, Cynthia M Mehta, Mansi Wildman, Horatio F Kloiber, Stacey Kirou, Kyriakos A Lyman, Stephen Crow, Mary K Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial |
title | Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial |
title_full | Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial |
title_fullStr | Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial |
title_full_unstemmed | Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial |
title_short | Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial |
title_sort | imatinib mesylate (gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase iia, single-arm, open-label clinical trial |
topic | Clinical and Epidemiological Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086082/ https://www.ncbi.nlm.nih.gov/pubmed/21398330 http://dx.doi.org/10.1136/ard.2010.143974 |
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