A multicenter, prospective, randomized, double‐blind, placebo‐controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma
Objective The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence‐based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in...
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| Veröffentlicht in: | Arthritis and rheumatism 2006-12, Vol.54 (12), p.3962-3970 |
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| creator | Hoyles, Rachel K. Ellis, Ross W. Wellsbury, Jessica Lees, Belinda Newlands, Pauline Goh, Nicole S. L. Roberts, Christopher Desai, Sujal Herrick, Ariane L. McHugh, Neil J. Foley, Noeleen M. Pearson, Stanley B. Emery, Paul Veale, Douglas J. Denton, Christopher P. Wells, Athol U. Black, Carol M. du Bois, Roland M. |
| description | Objective
The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence‐based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc.
Methods
Forty‐five patients were randomized to receive low‐dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single‐breath diffusing capacity for carbon monoxide (DLCO). Secondary outcome measures included changes in appearance on high‐resolution computed tomography and dyspnea scores. An intent‐to‐treat statistical analysis was performed.
Results
At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty‐two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non–trial‐related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between‐group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLCO or secondary outcome measures were identified.
Conclusion
This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low‐dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events. |
| doi_str_mv | 10.1002/art.22204 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_art_22204</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>ART22204</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4794-98c4f8a639e0875c57ec66f9469b69591da91aeba117cd56a09b59146f860f713</originalsourceid><addsrcrecordid>eNp1kU1qHDEQhUWIiSdOFrlA0CYLw7Qt9b-Wg0mcgMEQnHVTLZUYBXWrkbptxisfIffzLidxTWbAq6xElT7ee9Rj7JMUF1KI_BLifJHnuSjfsJWscpUJWci3bCWEKLOiUvKUvU_pN415URXv2KlsZFHUUqzY84YPi5-dxnHGuOZTDGlCPbt7XPMIowmDe0Sz5iYsvce_T39670aaJw8a-0ALHcY5Bu_R8Dk68DxYrkMkzZBIMziTOAlxRxjc4xiWxPVO-zBtyWsLgzPILQmEB5LodzxEEoFHmLcuTNGN-9_I5y2SPsI8UNS9x7T4IYwQd9y6nmK7RBY8aU-eBuMAH9iJBZ_w4_E9Y7--fb27-p7d3F7_uNrcZLpsVJmpVpe2hbpQKNqm0lWDuq6tKmvV14quZ0BJwB6kbLSpahCqp21Z27YWli55xs4PuppSpIi2o9QDBeuk6PYFdVRQ968gYj8f2GnpBzSv5LERAr4cAUgavKUOtEuvXFuULVVM3OWBe3Aed_937DY_7w7WLwqQsHE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>A multicenter, prospective, randomized, double‐blind, placebo‐controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma</title><source>Wiley Online Library - AutoHoldings Journals</source><source>MEDLINE</source><creator>Hoyles, Rachel K. ; Ellis, Ross W. ; Wellsbury, Jessica ; Lees, Belinda ; Newlands, Pauline ; Goh, Nicole S. L. ; Roberts, Christopher ; Desai, Sujal ; Herrick, Ariane L. ; McHugh, Neil J. ; Foley, Noeleen M. ; Pearson, Stanley B. ; Emery, Paul ; Veale, Douglas J. ; Denton, Christopher P. ; Wells, Athol U. ; Black, Carol M. ; du Bois, Roland M.</creator><creatorcontrib>Hoyles, Rachel K. ; Ellis, Ross W. ; Wellsbury, Jessica ; Lees, Belinda ; Newlands, Pauline ; Goh, Nicole S. L. ; Roberts, Christopher ; Desai, Sujal ; Herrick, Ariane L. ; McHugh, Neil J. ; Foley, Noeleen M. ; Pearson, Stanley B. ; Emery, Paul ; Veale, Douglas J. ; Denton, Christopher P. ; Wells, Athol U. ; Black, Carol M. ; du Bois, Roland M.</creatorcontrib><description>Objective
The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence‐based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc.
Methods
Forty‐five patients were randomized to receive low‐dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single‐breath diffusing capacity for carbon monoxide (DLCO). Secondary outcome measures included changes in appearance on high‐resolution computed tomography and dyspnea scores. An intent‐to‐treat statistical analysis was performed.
Results
At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty‐two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non–trial‐related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between‐group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLCO or secondary outcome measures were identified.
Conclusion
This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low‐dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events.</description><identifier>ISSN: 0004-3591</identifier><identifier>EISSN: 1529-0131</identifier><identifier>DOI: 10.1002/art.22204</identifier><identifier>PMID: 17133610</identifier><identifier>CODEN: ARHEAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Administration, Oral ; Adolescent ; Adult ; Aged ; Azathioprine - therapeutic use ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Cyclophosphamide - therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Glucocorticoids - therapeutic use ; Humans ; Immunosuppressive Agents - therapeutic use ; Injections, Intravenous ; Male ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Pneumology ; Prednisolone - therapeutic use ; Prospective Studies ; Pulmonary Fibrosis - drug therapy ; Pulmonary Fibrosis - etiology ; Pulmonary Fibrosis - physiopathology ; Respiratory Function Tests ; Respiratory system : syndromes and miscellaneous diseases ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; Scleroderma, Systemic - complications ; Scleroderma, Systemic - drug therapy ; Scleroderma, Systemic - physiopathology ; Treatment Outcome</subject><ispartof>Arthritis and rheumatism, 2006-12, Vol.54 (12), p.3962-3970</ispartof><rights>Copyright © 2006 by the American College of Rheumatology</rights><rights>2007 INIST-CNRS</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4794-98c4f8a639e0875c57ec66f9469b69591da91aeba117cd56a09b59146f860f713</citedby><cites>FETCH-LOGICAL-c4794-98c4f8a639e0875c57ec66f9469b69591da91aeba117cd56a09b59146f860f713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.22204$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.22204$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18348529$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17133610$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hoyles, Rachel K.</creatorcontrib><creatorcontrib>Ellis, Ross W.</creatorcontrib><creatorcontrib>Wellsbury, Jessica</creatorcontrib><creatorcontrib>Lees, Belinda</creatorcontrib><creatorcontrib>Newlands, Pauline</creatorcontrib><creatorcontrib>Goh, Nicole S. L.</creatorcontrib><creatorcontrib>Roberts, Christopher</creatorcontrib><creatorcontrib>Desai, Sujal</creatorcontrib><creatorcontrib>Herrick, Ariane L.</creatorcontrib><creatorcontrib>McHugh, Neil J.</creatorcontrib><creatorcontrib>Foley, Noeleen M.</creatorcontrib><creatorcontrib>Pearson, Stanley B.</creatorcontrib><creatorcontrib>Emery, Paul</creatorcontrib><creatorcontrib>Veale, Douglas J.</creatorcontrib><creatorcontrib>Denton, Christopher P.</creatorcontrib><creatorcontrib>Wells, Athol U.</creatorcontrib><creatorcontrib>Black, Carol M.</creatorcontrib><creatorcontrib>du Bois, Roland M.</creatorcontrib><title>A multicenter, prospective, randomized, double‐blind, placebo‐controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma</title><title>Arthritis and rheumatism</title><addtitle>Arthritis Rheum</addtitle><description>Objective
The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence‐based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc.
Methods
Forty‐five patients were randomized to receive low‐dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single‐breath diffusing capacity for carbon monoxide (DLCO). Secondary outcome measures included changes in appearance on high‐resolution computed tomography and dyspnea scores. An intent‐to‐treat statistical analysis was performed.
Results
At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty‐two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non–trial‐related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between‐group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLCO or secondary outcome measures were identified.
Conclusion
This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low‐dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events.</description><subject>Administration, Oral</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Azathioprine - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Cyclophosphamide - therapeutic use</subject><subject>Double-Blind Method</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Glucocorticoids - therapeutic use</subject><subject>Humans</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Pneumology</subject><subject>Prednisolone - therapeutic use</subject><subject>Prospective Studies</subject><subject>Pulmonary Fibrosis - drug therapy</subject><subject>Pulmonary Fibrosis - etiology</subject><subject>Pulmonary Fibrosis - physiopathology</subject><subject>Respiratory Function Tests</subject><subject>Respiratory system : syndromes and miscellaneous diseases</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><subject>Scleroderma, Systemic - complications</subject><subject>Scleroderma, Systemic - drug therapy</subject><subject>Scleroderma, Systemic - physiopathology</subject><subject>Treatment Outcome</subject><issn>0004-3591</issn><issn>1529-0131</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1qHDEQhUWIiSdOFrlA0CYLw7Qt9b-Wg0mcgMEQnHVTLZUYBXWrkbptxisfIffzLidxTWbAq6xElT7ee9Rj7JMUF1KI_BLifJHnuSjfsJWscpUJWci3bCWEKLOiUvKUvU_pN415URXv2KlsZFHUUqzY84YPi5-dxnHGuOZTDGlCPbt7XPMIowmDe0Sz5iYsvce_T39670aaJw8a-0ALHcY5Bu_R8Dk68DxYrkMkzZBIMziTOAlxRxjc4xiWxPVO-zBtyWsLgzPILQmEB5LodzxEEoFHmLcuTNGN-9_I5y2SPsI8UNS9x7T4IYwQd9y6nmK7RBY8aU-eBuMAH9iJBZ_w4_E9Y7--fb27-p7d3F7_uNrcZLpsVJmpVpe2hbpQKNqm0lWDuq6tKmvV14quZ0BJwB6kbLSpahCqp21Z27YWli55xs4PuppSpIi2o9QDBeuk6PYFdVRQ968gYj8f2GnpBzSv5LERAr4cAUgavKUOtEuvXFuULVVM3OWBe3Aed_937DY_7w7WLwqQsHE</recordid><startdate>200612</startdate><enddate>200612</enddate><creator>Hoyles, Rachel K.</creator><creator>Ellis, Ross W.</creator><creator>Wellsbury, Jessica</creator><creator>Lees, Belinda</creator><creator>Newlands, Pauline</creator><creator>Goh, Nicole S. L.</creator><creator>Roberts, Christopher</creator><creator>Desai, Sujal</creator><creator>Herrick, Ariane L.</creator><creator>McHugh, Neil J.</creator><creator>Foley, Noeleen M.</creator><creator>Pearson, Stanley B.</creator><creator>Emery, Paul</creator><creator>Veale, Douglas J.</creator><creator>Denton, Christopher P.</creator><creator>Wells, Athol U.</creator><creator>Black, Carol M.</creator><creator>du Bois, Roland M.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>200612</creationdate><title>A multicenter, prospective, randomized, double‐blind, placebo‐controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma</title><author>Hoyles, Rachel K. ; Ellis, Ross W. ; Wellsbury, Jessica ; Lees, Belinda ; Newlands, Pauline ; Goh, Nicole S. L. ; Roberts, Christopher ; Desai, Sujal ; Herrick, Ariane L. ; McHugh, Neil J. ; Foley, Noeleen M. ; Pearson, Stanley B. ; Emery, Paul ; Veale, Douglas J. ; Denton, Christopher P. ; Wells, Athol U. ; Black, Carol M. ; du Bois, Roland M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4794-98c4f8a639e0875c57ec66f9469b69591da91aeba117cd56a09b59146f860f713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Administration, Oral</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Azathioprine - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Cyclophosphamide - therapeutic use</topic><topic>Double-Blind Method</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Glucocorticoids - therapeutic use</topic><topic>Humans</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Pneumology</topic><topic>Prednisolone - therapeutic use</topic><topic>Prospective Studies</topic><topic>Pulmonary Fibrosis - drug therapy</topic><topic>Pulmonary Fibrosis - etiology</topic><topic>Pulmonary Fibrosis - physiopathology</topic><topic>Respiratory Function Tests</topic><topic>Respiratory system : syndromes and miscellaneous diseases</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><topic>Scleroderma, Systemic - complications</topic><topic>Scleroderma, Systemic - drug therapy</topic><topic>Scleroderma, Systemic - physiopathology</topic><topic>Treatment Outcome</topic><toplevel>online_resources</toplevel><creatorcontrib>Hoyles, Rachel K.</creatorcontrib><creatorcontrib>Ellis, Ross W.</creatorcontrib><creatorcontrib>Wellsbury, Jessica</creatorcontrib><creatorcontrib>Lees, Belinda</creatorcontrib><creatorcontrib>Newlands, Pauline</creatorcontrib><creatorcontrib>Goh, Nicole S. L.</creatorcontrib><creatorcontrib>Roberts, Christopher</creatorcontrib><creatorcontrib>Desai, Sujal</creatorcontrib><creatorcontrib>Herrick, Ariane L.</creatorcontrib><creatorcontrib>McHugh, Neil J.</creatorcontrib><creatorcontrib>Foley, Noeleen M.</creatorcontrib><creatorcontrib>Pearson, Stanley B.</creatorcontrib><creatorcontrib>Emery, Paul</creatorcontrib><creatorcontrib>Veale, Douglas J.</creatorcontrib><creatorcontrib>Denton, Christopher P.</creatorcontrib><creatorcontrib>Wells, Athol U.</creatorcontrib><creatorcontrib>Black, Carol M.</creatorcontrib><creatorcontrib>du Bois, Roland M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Arthritis and rheumatism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hoyles, Rachel K.</au><au>Ellis, Ross W.</au><au>Wellsbury, Jessica</au><au>Lees, Belinda</au><au>Newlands, Pauline</au><au>Goh, Nicole S. L.</au><au>Roberts, Christopher</au><au>Desai, Sujal</au><au>Herrick, Ariane L.</au><au>McHugh, Neil J.</au><au>Foley, Noeleen M.</au><au>Pearson, Stanley B.</au><au>Emery, Paul</au><au>Veale, Douglas J.</au><au>Denton, Christopher P.</au><au>Wells, Athol U.</au><au>Black, Carol M.</au><au>du Bois, Roland M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A multicenter, prospective, randomized, double‐blind, placebo‐controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma</atitle><jtitle>Arthritis and rheumatism</jtitle><addtitle>Arthritis Rheum</addtitle><date>2006-12</date><risdate>2006</risdate><volume>54</volume><issue>12</issue><spage>3962</spage><epage>3970</epage><pages>3962-3970</pages><issn>0004-3591</issn><eissn>1529-0131</eissn><coden>ARHEAW</coden><abstract>Objective
The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence‐based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc.
Methods
Forty‐five patients were randomized to receive low‐dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single‐breath diffusing capacity for carbon monoxide (DLCO). Secondary outcome measures included changes in appearance on high‐resolution computed tomography and dyspnea scores. An intent‐to‐treat statistical analysis was performed.
Results
At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty‐two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non–trial‐related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between‐group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLCO or secondary outcome measures were identified.
Conclusion
This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low‐dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>17133610</pmid><doi>10.1002/art.22204</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0004-3591 |
| ispartof | Arthritis and rheumatism, 2006-12, Vol.54 (12), p.3962-3970 |
| issn | 0004-3591 1529-0131 |
| language | eng |
| recordid | cdi_crossref_primary_10_1002_art_22204 |
| source | Wiley Online Library - AutoHoldings Journals; MEDLINE |
| subjects | Administration, Oral Adolescent Adult Aged Azathioprine - therapeutic use Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Cyclophosphamide - therapeutic use Double-Blind Method Drug Therapy, Combination Female Glucocorticoids - therapeutic use Humans Immunosuppressive Agents - therapeutic use Injections, Intravenous Male Medical sciences Middle Aged Pharmacology. Drug treatments Pneumology Prednisolone - therapeutic use Prospective Studies Pulmonary Fibrosis - drug therapy Pulmonary Fibrosis - etiology Pulmonary Fibrosis - physiopathology Respiratory Function Tests Respiratory system : syndromes and miscellaneous diseases Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis Scleroderma, Systemic - complications Scleroderma, Systemic - drug therapy Scleroderma, Systemic - physiopathology Treatment Outcome |
| title | A multicenter, prospective, randomized, double‐blind, placebo‐controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma |
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