Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients with Ulcerative Colitis: A Randomized Clinical Trial

Samuel P Costello, Patrick A Hughes, Oliver Waters, Robert V Bryant, Andrew D Vincent, Paul Blatchford, Rosa Katsikeros, Jesica Makanyanga, Melissa A Campaniello, Chris Mavrangelos, Carly P Rosewarne, Chelsea Bickley, Cian Peters, Mark N Schoeman, Michael A Conlon, Ian C Roberts-Thomson, Jane M Andrews

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Abstract

Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity.

Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool.

Design, Setting, and Participants: A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017.

Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months.

Main Outcomes and Measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events.

Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group.

Conclusions and Relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.

Trial Registration: anzctr.org.au Identifier: ACTRN12613000236796.

LanguageEnglish
Pages156-164
Number of pages9
JournalJAMA : the journal of the American Medical Association
Volume321
Issue number2
DOIs
Publication statusPublished - 15 Jan 2019

Keywords

  • Journal Article

Cite this

Costello, Samuel P ; Hughes, Patrick A ; Waters, Oliver ; Bryant, Robert V ; Vincent, Andrew D ; Blatchford, Paul ; Katsikeros, Rosa ; Makanyanga, Jesica ; Campaniello, Melissa A ; Mavrangelos, Chris ; Rosewarne, Carly P ; Bickley, Chelsea ; Peters, Cian ; Schoeman, Mark N ; Conlon, Michael A ; Roberts-Thomson, Ian C ; Andrews, Jane M. / Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients with Ulcerative Colitis : A Randomized Clinical Trial. In: JAMA : the journal of the American Medical Association. 2019 ; Vol. 321, No. 2. pp. 156-164.
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abstract = "Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity.Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool.Design, Setting, and Participants: A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017.Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months.Main Outcomes and Measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events.Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45{\%}]), 69 (95{\%}) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32{\%}) receiving pooled donor FMT compared with 3 of the 35 (9{\%}) receiving autologous FMT (difference, 23{\%} [95{\%} CI, 4{\%}-42{\%}]; odds ratio, 5.0 [95{\%} CI, 1.2-20.1]; P = .03). Five of the 12 participants (42{\%}) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group.Conclusions and Relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.Trial Registration: anzctr.org.au Identifier: ACTRN12613000236796.",
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author = "Costello, {Samuel P} and Hughes, {Patrick A} and Oliver Waters and Bryant, {Robert V} and Vincent, {Andrew D} and Paul Blatchford and Rosa Katsikeros and Jesica Makanyanga and Campaniello, {Melissa A} and Chris Mavrangelos and Rosewarne, {Carly P} and Chelsea Bickley and Cian Peters and Schoeman, {Mark N} and Conlon, {Michael A} and Roberts-Thomson, {Ian C} and Andrews, {Jane M}",
year = "2019",
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Costello, SP, Hughes, PA, Waters, O, Bryant, RV, Vincent, AD, Blatchford, P, Katsikeros, R, Makanyanga, J, Campaniello, MA, Mavrangelos, C, Rosewarne, CP, Bickley, C, Peters, C, Schoeman, MN, Conlon, MA, Roberts-Thomson, IC & Andrews, JM 2019, 'Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients with Ulcerative Colitis: A Randomized Clinical Trial', JAMA : the journal of the American Medical Association, vol. 321, no. 2, pp. 156-164. https://doi.org/10.1001/jama.2018.20046, https://doi.org/10.1001/jama.2018.20046

Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients with Ulcerative Colitis : A Randomized Clinical Trial. / Costello, Samuel P; Hughes, Patrick A; Waters, Oliver; Bryant, Robert V; Vincent, Andrew D; Blatchford, Paul; Katsikeros, Rosa; Makanyanga, Jesica; Campaniello, Melissa A; Mavrangelos, Chris; Rosewarne, Carly P; Bickley, Chelsea; Peters, Cian; Schoeman, Mark N; Conlon, Michael A; Roberts-Thomson, Ian C; Andrews, Jane M.

In: JAMA : the journal of the American Medical Association, Vol. 321, No. 2, 15.01.2019, p. 156-164.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients with Ulcerative Colitis

T2 - JAMA : the journal of the American Medical Association

AU - Costello, Samuel P

AU - Hughes, Patrick A

AU - Waters, Oliver

AU - Bryant, Robert V

AU - Vincent, Andrew D

AU - Blatchford, Paul

AU - Katsikeros, Rosa

AU - Makanyanga, Jesica

AU - Campaniello, Melissa A

AU - Mavrangelos, Chris

AU - Rosewarne, Carly P

AU - Bickley, Chelsea

AU - Peters, Cian

AU - Schoeman, Mark N

AU - Conlon, Michael A

AU - Roberts-Thomson, Ian C

AU - Andrews, Jane M

PY - 2019/1/15

Y1 - 2019/1/15

N2 - Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity.Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool.Design, Setting, and Participants: A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017.Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months.Main Outcomes and Measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events.Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group.Conclusions and Relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.Trial Registration: anzctr.org.au Identifier: ACTRN12613000236796.

AB - Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity.Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool.Design, Setting, and Participants: A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017.Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months.Main Outcomes and Measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events.Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group.Conclusions and Relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.Trial Registration: anzctr.org.au Identifier: ACTRN12613000236796.

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