Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial
Summary Background Complex perianal fistulas in Crohn's disease are challenging to treat. Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach. We aimed to assess the safety and efficacy of Cx601 for treatment-refractory complex perianal fistulas in...
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| Veröffentlicht in: | The Lancet (British edition) 2016-09, Vol.388 (10051), p.1281-1290 |
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| creator | Panés, Julián, Prof García-Olmo, Damián, MD Van Assche, Gert, Prof Colombel, Jean Frederic, Prof Reinisch, Walter, Prof Baumgart, Daniel C, Prof Dignass, Axel, Prof Nachury, Maria, MD Ferrante, Marc, Prof Kazemi-Shirazi, Lili, Prof Grimaud, Jean C, Prof de la Portilla, Fernando, Prof Goldin, Eran, Prof Richard, Marie Paule, MD Leselbaum, Anne, MD Danese, Silvio, Prof |
| description | Summary Background Complex perianal fistulas in Crohn's disease are challenging to treat. Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach. We aimed to assess the safety and efficacy of Cx601 for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Methods We did this randomised, double-blind, parallel-group, placebo-controlled study at 49 hospitals in seven European countries and Israel from July 6, 2012, to July 27, 2015. Adult patients (≥18 years) with Crohn's disease and treatment-refractory, draining complex perianal fistulas were randomly assigned (1:1) using a pre-established randomisation list to a single intralesional injection of 120 million Cx601 cells or 24 mL saline solution (placebo), with stratification according to concomitant baseline treatment. Treatment was administered by an unmasked surgeon, with a masked gastroenterologist and radiologist assessing the therapeutic effect. The primary endpoint was combined remission at week 24 (ie, clinical assessment of closure of all treated external openings that were draining at baseline, and absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI). Efficacy was assessed in the intention-to-treat (ITT) and modified ITT populations; safety was assessed in the safety population. This study is registered with ClinicalTrials.gov , number NCT01541579. Findings 212 patients were randomly assigned: 107 to Cx601 and 105 to placebo. A significantly greater proportion of patients treated with Cx601 versus placebo achieved combined remission in the ITT (53 of 107 [50%] vs 36 of 105 [34%]; difference 15·2%, 97·5% CI 0·2–30·3; p=0·024) and modified ITT populations (53 of 103 [51%] vs 36 of 101 [36%]; 15·8%, 0·5–31·2; p=0·021). 18 (17%) of 103 patients in the Cx601 group versus 30 (29%) of 103 in the placebo group experienced treatment-related adverse events, the most common of which were anal abscess (six in the Cx601 group vs nine in the placebo group) and proctalgia (five vs nine). Interpretation Cx601 is an effective and safe treatment for complex perianal fistulas in patients with Crohn's disease who did not respond to conventional or biological treatments, or both. Funding TiGenix. |
| doi_str_mv | 10.1016/S0140-6736(16)31203-X |
| format | Article |
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Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach. We aimed to assess the safety and efficacy of Cx601 for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Methods We did this randomised, double-blind, parallel-group, placebo-controlled study at 49 hospitals in seven European countries and Israel from July 6, 2012, to July 27, 2015. Adult patients (≥18 years) with Crohn's disease and treatment-refractory, draining complex perianal fistulas were randomly assigned (1:1) using a pre-established randomisation list to a single intralesional injection of 120 million Cx601 cells or 24 mL saline solution (placebo), with stratification according to concomitant baseline treatment. Treatment was administered by an unmasked surgeon, with a masked gastroenterologist and radiologist assessing the therapeutic effect. The primary endpoint was combined remission at week 24 (ie, clinical assessment of closure of all treated external openings that were draining at baseline, and absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI). Efficacy was assessed in the intention-to-treat (ITT) and modified ITT populations; safety was assessed in the safety population. This study is registered with ClinicalTrials.gov , number NCT01541579. Findings 212 patients were randomly assigned: 107 to Cx601 and 105 to placebo. A significantly greater proportion of patients treated with Cx601 versus placebo achieved combined remission in the ITT (53 of 107 [50%] vs 36 of 105 [34%]; difference 15·2%, 97·5% CI 0·2–30·3; p=0·024) and modified ITT populations (53 of 103 [51%] vs 36 of 101 [36%]; 15·8%, 0·5–31·2; p=0·021). 18 (17%) of 103 patients in the Cx601 group versus 30 (29%) of 103 in the placebo group experienced treatment-related adverse events, the most common of which were anal abscess (six in the Cx601 group vs nine in the placebo group) and proctalgia (five vs nine). Interpretation Cx601 is an effective and safe treatment for complex perianal fistulas in patients with Crohn's disease who did not respond to conventional or biological treatments, or both. Funding TiGenix.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(16)31203-X</identifier><identifier>PMID: 27477896</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adipose Tissue ; Adult ; Aged ; Biological treatment ; Clinical trials ; Combined Modality Therapy ; Crohn Disease - complications ; Crohn's disease ; Double-Blind Method ; Europe ; Evidence-Based Medicine ; Female ; Humans ; Inflammation ; Internal Medicine ; Israel ; Male ; Medical treatment ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Middle Aged ; Rectal Fistula - etiology ; Rectal Fistula - pathology ; Rectal Fistula - surgery ; Rectal Fistula - therapy ; Safety ; Stem cells ; Transplantation, Homologous ; Treatment Outcome ; Tumor necrosis factor-TNF</subject><ispartof>The Lancet (British edition), 2016-09, Vol.388 (10051), p.1281-1290</ispartof><rights>Elsevier Ltd</rights><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Sep 24, 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-58730048acc507c2d6e7334819f5a36a2afebcdb381fc95a0defe2219a0d815c3</citedby><cites>FETCH-LOGICAL-c533t-58730048acc507c2d6e7334819f5a36a2afebcdb381fc95a0defe2219a0d815c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1822843480?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976,64364,64366,64368,72218</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27477896$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Panés, Julián, Prof</creatorcontrib><creatorcontrib>García-Olmo, Damián, MD</creatorcontrib><creatorcontrib>Van Assche, Gert, Prof</creatorcontrib><creatorcontrib>Colombel, Jean Frederic, Prof</creatorcontrib><creatorcontrib>Reinisch, Walter, Prof</creatorcontrib><creatorcontrib>Baumgart, Daniel C, Prof</creatorcontrib><creatorcontrib>Dignass, Axel, Prof</creatorcontrib><creatorcontrib>Nachury, Maria, MD</creatorcontrib><creatorcontrib>Ferrante, Marc, Prof</creatorcontrib><creatorcontrib>Kazemi-Shirazi, Lili, Prof</creatorcontrib><creatorcontrib>Grimaud, Jean C, Prof</creatorcontrib><creatorcontrib>de la Portilla, Fernando, Prof</creatorcontrib><creatorcontrib>Goldin, Eran, Prof</creatorcontrib><creatorcontrib>Richard, Marie Paule, MD</creatorcontrib><creatorcontrib>Leselbaum, Anne, MD</creatorcontrib><creatorcontrib>Danese, Silvio, Prof</creatorcontrib><creatorcontrib>ADMIRE CD Study Group Collaborators</creatorcontrib><title>Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Summary Background Complex perianal fistulas in Crohn's disease are challenging to treat. Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach. We aimed to assess the safety and efficacy of Cx601 for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Methods We did this randomised, double-blind, parallel-group, placebo-controlled study at 49 hospitals in seven European countries and Israel from July 6, 2012, to July 27, 2015. Adult patients (≥18 years) with Crohn's disease and treatment-refractory, draining complex perianal fistulas were randomly assigned (1:1) using a pre-established randomisation list to a single intralesional injection of 120 million Cx601 cells or 24 mL saline solution (placebo), with stratification according to concomitant baseline treatment. Treatment was administered by an unmasked surgeon, with a masked gastroenterologist and radiologist assessing the therapeutic effect. The primary endpoint was combined remission at week 24 (ie, clinical assessment of closure of all treated external openings that were draining at baseline, and absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI). Efficacy was assessed in the intention-to-treat (ITT) and modified ITT populations; safety was assessed in the safety population. This study is registered with ClinicalTrials.gov , number NCT01541579. Findings 212 patients were randomly assigned: 107 to Cx601 and 105 to placebo. A significantly greater proportion of patients treated with Cx601 versus placebo achieved combined remission in the ITT (53 of 107 [50%] vs 36 of 105 [34%]; difference 15·2%, 97·5% CI 0·2–30·3; p=0·024) and modified ITT populations (53 of 103 [51%] vs 36 of 101 [36%]; 15·8%, 0·5–31·2; p=0·021). 18 (17%) of 103 patients in the Cx601 group versus 30 (29%) of 103 in the placebo group experienced treatment-related adverse events, the most common of which were anal abscess (six in the Cx601 group vs nine in the placebo group) and proctalgia (five vs nine). Interpretation Cx601 is an effective and safe treatment for complex perianal fistulas in patients with Crohn's disease who did not respond to conventional or biological treatments, or both. Funding TiGenix.</description><subject>Adipose Tissue</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological treatment</subject><subject>Clinical trials</subject><subject>Combined Modality Therapy</subject><subject>Crohn Disease - complications</subject><subject>Crohn's disease</subject><subject>Double-Blind Method</subject><subject>Europe</subject><subject>Evidence-Based Medicine</subject><subject>Female</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Internal Medicine</subject><subject>Israel</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal Stromal Cells</subject><subject>Middle Aged</subject><subject>Rectal Fistula - etiology</subject><subject>Rectal Fistula - pathology</subject><subject>Rectal Fistula - surgery</subject><subject>Rectal Fistula - therapy</subject><subject>Safety</subject><subject>Stem cells</subject><subject>Transplantation, 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allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial</title><author>Panés, Julián, Prof ; García-Olmo, Damián, MD ; Van Assche, Gert, Prof ; Colombel, Jean Frederic, Prof ; Reinisch, Walter, Prof ; Baumgart, Daniel C, Prof ; Dignass, Axel, Prof ; Nachury, Maria, MD ; Ferrante, Marc, Prof ; Kazemi-Shirazi, Lili, Prof ; Grimaud, Jean C, Prof ; de la Portilla, Fernando, Prof ; Goldin, Eran, Prof ; Richard, Marie Paule, MD ; Leselbaum, Anne, MD ; Danese, Silvio, Prof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-58730048acc507c2d6e7334819f5a36a2afebcdb381fc95a0defe2219a0d815c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adipose Tissue</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological treatment</topic><topic>Clinical trials</topic><topic>Combined Modality Therapy</topic><topic>Crohn Disease - complications</topic><topic>Crohn's disease</topic><topic>Double-Blind Method</topic><topic>Europe</topic><topic>Evidence-Based Medicine</topic><topic>Female</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Internal Medicine</topic><topic>Israel</topic><topic>Male</topic><topic>Medical treatment</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchymal Stromal Cells</topic><topic>Middle Aged</topic><topic>Rectal Fistula - etiology</topic><topic>Rectal Fistula - pathology</topic><topic>Rectal Fistula - surgery</topic><topic>Rectal Fistula - therapy</topic><topic>Safety</topic><topic>Stem cells</topic><topic>Transplantation, Homologous</topic><topic>Treatment Outcome</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Panés, Julián, Prof</creatorcontrib><creatorcontrib>García-Olmo, Damián, 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Psychology</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Panés, Julián, Prof</au><au>García-Olmo, Damián, MD</au><au>Van Assche, Gert, Prof</au><au>Colombel, Jean Frederic, Prof</au><au>Reinisch, Walter, Prof</au><au>Baumgart, Daniel C, Prof</au><au>Dignass, Axel, Prof</au><au>Nachury, Maria, MD</au><au>Ferrante, Marc, Prof</au><au>Kazemi-Shirazi, Lili, Prof</au><au>Grimaud, Jean C, Prof</au><au>de la Portilla, Fernando, Prof</au><au>Goldin, Eran, Prof</au><au>Richard, Marie Paule, MD</au><au>Leselbaum, Anne, MD</au><au>Danese, Silvio, Prof</au><aucorp>ADMIRE CD Study Group Collaborators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2016-09-24</date><risdate>2016</risdate><volume>388</volume><issue>10051</issue><spage>1281</spage><epage>1290</epage><pages>1281-1290</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Summary Background Complex perianal fistulas in Crohn's disease are challenging to treat. Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach. We aimed to assess the safety and efficacy of Cx601 for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Methods We did this randomised, double-blind, parallel-group, placebo-controlled study at 49 hospitals in seven European countries and Israel from July 6, 2012, to July 27, 2015. Adult patients (≥18 years) with Crohn's disease and treatment-refractory, draining complex perianal fistulas were randomly assigned (1:1) using a pre-established randomisation list to a single intralesional injection of 120 million Cx601 cells or 24 mL saline solution (placebo), with stratification according to concomitant baseline treatment. Treatment was administered by an unmasked surgeon, with a masked gastroenterologist and radiologist assessing the therapeutic effect. The primary endpoint was combined remission at week 24 (ie, clinical assessment of closure of all treated external openings that were draining at baseline, and absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI). Efficacy was assessed in the intention-to-treat (ITT) and modified ITT populations; safety was assessed in the safety population. This study is registered with ClinicalTrials.gov , number NCT01541579. Findings 212 patients were randomly assigned: 107 to Cx601 and 105 to placebo. A significantly greater proportion of patients treated with Cx601 versus placebo achieved combined remission in the ITT (53 of 107 [50%] vs 36 of 105 [34%]; difference 15·2%, 97·5% CI 0·2–30·3; p=0·024) and modified ITT populations (53 of 103 [51%] vs 36 of 101 [36%]; 15·8%, 0·5–31·2; p=0·021). 18 (17%) of 103 patients in the Cx601 group versus 30 (29%) of 103 in the placebo group experienced treatment-related adverse events, the most common of which were anal abscess (six in the Cx601 group vs nine in the placebo group) and proctalgia (five vs nine). Interpretation Cx601 is an effective and safe treatment for complex perianal fistulas in patients with Crohn's disease who did not respond to conventional or biological treatments, or both. Funding TiGenix.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27477896</pmid><doi>10.1016/S0140-6736(16)31203-X</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2016-09, Vol.388 (10051), p.1281-1290 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1832245515 |
| source | MEDLINE; Elsevier ScienceDirect Journals; ProQuest Central UK/Ireland |
| subjects | Adipose Tissue Adult Aged Biological treatment Clinical trials Combined Modality Therapy Crohn Disease - complications Crohn's disease Double-Blind Method Europe Evidence-Based Medicine Female Humans Inflammation Internal Medicine Israel Male Medical treatment Mesenchymal Stem Cell Transplantation Mesenchymal Stromal Cells Middle Aged Rectal Fistula - etiology Rectal Fistula - pathology Rectal Fistula - surgery Rectal Fistula - therapy Safety Stem cells Transplantation, Homologous Treatment Outcome Tumor necrosis factor-TNF |
| title | Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial |
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