John A. Snowden
Autologous stem cell transplantation in refractory Crohn’s disease – low intensity therapy evaluation (ASTIClite): study protocols for a multicentre, randomised controlled trial and observational follow up study
Snowden, John A.; Hawkey, Chris; Hind, Daniel; Swaby, Lizzie; Mellor, Katie; Emsley, Richard; Mandefield, Laura; Lee, Ellen; Badoglio, Manuela; Polge, Emmanuelle; Labopin, Myriam; Gribben, John; Pockley, A. Graham; Foulds, Gemma A.; Lobo, Alan; Travis, Simon; Parkes, Miles; Satsangi, Jack; Papaioannou, Diana; Lindsay, James O.; Autologous Stem Cell Transplantation In Refractory CD -Low Intensity Therapy Evaluation Study Investigators; European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP)
Authors
Chris Hawkey
Daniel Hind
Lizzie Swaby
Katie Mellor
Richard Emsley
Laura Mandefield
Ellen Lee
Manuela Badoglio
Emmanuelle Polge
Myriam Labopin
John Gribben
A. Graham Pockley
Gemma A. Foulds
Alan Lobo
Simon Travis
Miles Parkes
Jack Satsangi
Diana Papaioannou
James O. Lindsay
Autologous Stem Cell Transplantation In Refractory CD -Low Intensity Therapy Evaluation Study Investigators
European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP)
Contributors
GORDON MORAN GORDON.MORAN@NOTTINGHAM.AC.UK
Researcher
Abstract
Background
Intestinal inflammation in Crohn’s disease (CD) is caused by mucosal immune system reactivity to luminal antigen and results in debilitating symptoms, reduced quality of life, impaired work productivity and significant health care costs. Not all patients respond to conventional and biologic therapies, with chronic inflammation ensuing. Although surgical resection may be required, disease frequently returns and surgery may not be an option, or may be declined. Case reports suggest potential benefit after haematopoietic stem cell transplant (HSCT) for patients with refractory CD.
The ASTIC trial asked whether HSCT could cure CD. Few patients achieved the primary endpoint of clinical remission for 3 months, off all medication with no evidence of active disease, and there were a high number of adverse events (AEs) and serious adverse events (SAEs), including one patient death. However, beneficial effects were observed in some aspects of disease activity. The ASTIClite trial will investigate these potential benefits and safety using a lower intensity regimen than ASTIC.
Methods
Ninety-nine participants will be recruited from secondary care IBD centres in the UK into a multicentre, randomised controlled trial (RCT, ASTIClite) and an observational follow-up, and randomised to autologous HSCT versus standard care (ratio 2:1).
The primary endpoint is treatment success at week 48, defined as mucosal healing without surgery or death. Secondary endpoints relating to efficacy, safety and mechanistic analyses will be evaluated at week 8, 14, 24, 32, 40 and 48.
Long-term safety of the low intensity HSCT regimen forms the primary endpoint for the EBMT follow-up study and will be assessed annually for 4–7 years.
Discussion
ASTIClite will compare HSCTlite with standard care with respect to safety, efficacy and quality of life, and capture outcomes allowing findings to be generalised to current clinical practice in the UK. It will also provide significant mechanistic insights into the immunological consequences of HSCTlite and its impact on treatment outcomes. The observational follow-up will provide information, which is currently unavailable for this population.
Journal Article Type | Article |
---|---|
Acceptance Date | May 1, 2019 |
Online Publication Date | May 31, 2019 |
Publication Date | May 31, 2019 |
Deposit Date | Jul 26, 2019 |
Publicly Available Date | Jul 26, 2019 |
Journal | BMC Gastroenterology |
Electronic ISSN | 1471-230X |
Publisher | Springer Verlag |
Peer Reviewed | Peer Reviewed |
Volume | 19 |
Article Number | 82 |
DOI | https://doi.org/10.1186/s12876-019-0992-2 |
Keywords | Gastroenterology; General medicine |
Public URL | https://nottingham-repository.worktribe.com/output/2346323 |
Publisher URL | https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-019-0992-2 |
Files
Autologous Stem Cell Transplantation
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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