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Prospective randomised controlled trial of adults with perianal fistulising Crohn’s disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol

INTRODUCTION: Perianal fistulising Crohn’s disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeu...

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Autores principales: Gu, Bonita, De Gregorio, Michael, Pipicella, Joseph Louis, Vande Casteele, Niels, Andrews, Jane M, Begun, Jakob, Connell, William, D’Souza, Basil, Gholamrezaei, Ali, Hart, Ailsa, Liew, Danny, Radford-Smith, Graham, Rimola, Jordi, Sutherland, Tom, Toong, Catherine, Woods, Rodney, Wu, Yang, Xuan, Wei, Williams, Astrid-Jane, Ng, Watson, Ding, Nik Sheng, Connor, Susan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252869/
https://www.ncbi.nlm.nih.gov/pubmed/34210720
http://dx.doi.org/10.1136/bmjopen-2020-043921
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author Gu, Bonita
De Gregorio, Michael
Pipicella, Joseph Louis
Vande Casteele, Niels
Andrews, Jane M
Begun, Jakob
Connell, William
D’Souza, Basil
Gholamrezaei, Ali
Hart, Ailsa
Liew, Danny
Radford-Smith, Graham
Rimola, Jordi
Sutherland, Tom
Toong, Catherine
Woods, Rodney
Wu, Yang
Xuan, Wei
Williams, Astrid-Jane
Ng, Watson
Ding, Nik Sheng
Connor, Susan
author_facet Gu, Bonita
De Gregorio, Michael
Pipicella, Joseph Louis
Vande Casteele, Niels
Andrews, Jane M
Begun, Jakob
Connell, William
D’Souza, Basil
Gholamrezaei, Ali
Hart, Ailsa
Liew, Danny
Radford-Smith, Graham
Rimola, Jordi
Sutherland, Tom
Toong, Catherine
Woods, Rodney
Wu, Yang
Xuan, Wei
Williams, Astrid-Jane
Ng, Watson
Ding, Nik Sheng
Connor, Susan
author_sort Gu, Bonita
collection PubMed
description INTRODUCTION: Perianal fistulising Crohn’s disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy. METHODS AND ANALYSIS: Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18–80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate. ETHICS AND DISSEMINATION: Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.
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spelling pubmed-82528692021-07-23 Prospective randomised controlled trial of adults with perianal fistulising Crohn’s disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol Gu, Bonita De Gregorio, Michael Pipicella, Joseph Louis Vande Casteele, Niels Andrews, Jane M Begun, Jakob Connell, William D’Souza, Basil Gholamrezaei, Ali Hart, Ailsa Liew, Danny Radford-Smith, Graham Rimola, Jordi Sutherland, Tom Toong, Catherine Woods, Rodney Wu, Yang Xuan, Wei Williams, Astrid-Jane Ng, Watson Ding, Nik Sheng Connor, Susan BMJ Open Gastroenterology and Hepatology INTRODUCTION: Perianal fistulising Crohn’s disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy. METHODS AND ANALYSIS: Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18–80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate. ETHICS AND DISSEMINATION: Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results. BMJ Publishing Group 2021-07-01 /pmc/articles/PMC8252869/ /pubmed/34210720 http://dx.doi.org/10.1136/bmjopen-2020-043921 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Gastroenterology and Hepatology
Gu, Bonita
De Gregorio, Michael
Pipicella, Joseph Louis
Vande Casteele, Niels
Andrews, Jane M
Begun, Jakob
Connell, William
D’Souza, Basil
Gholamrezaei, Ali
Hart, Ailsa
Liew, Danny
Radford-Smith, Graham
Rimola, Jordi
Sutherland, Tom
Toong, Catherine
Woods, Rodney
Wu, Yang
Xuan, Wei
Williams, Astrid-Jane
Ng, Watson
Ding, Nik Sheng
Connor, Susan
Prospective randomised controlled trial of adults with perianal fistulising Crohn’s disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol
title Prospective randomised controlled trial of adults with perianal fistulising Crohn’s disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol
title_full Prospective randomised controlled trial of adults with perianal fistulising Crohn’s disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol
title_fullStr Prospective randomised controlled trial of adults with perianal fistulising Crohn’s disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol
title_full_unstemmed Prospective randomised controlled trial of adults with perianal fistulising Crohn’s disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol
title_short Prospective randomised controlled trial of adults with perianal fistulising Crohn’s disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol
title_sort prospective randomised controlled trial of adults with perianal fistulising crohn’s disease and optimised therapeutic infliximab levels: proactive trial study protocol
topic Gastroenterology and Hepatology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252869/
https://www.ncbi.nlm.nih.gov/pubmed/34210720
http://dx.doi.org/10.1136/bmjopen-2020-043921
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