FMT in IBD Walter Reinisch Department of Medicine McMaster University Hamilton, ON.
FMT in Pediatric IBD
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Transcript of FMT in Pediatric IBD
FMT in Pediatric IBD
Michael Docktor, MDBoston Children’s Hospital
August 16, 2014
Disclosures
• I have no relevant disclosures or financial obligations
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Outline
I. Brief backgroundII. Anecdotal experience at Boston
Children’sIII. Oh and by the way, they have IBDIV. Pediatric FMT in ulcerative colitisV. Pediatric FMT in Crohn’s diseaseVI.Future directions
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Kostic, et al. Gastro. 2014; 146(5): 1489-1499
Our experience: FMT for IBD“Innovative Therapy”
• 7 patients with recalcitrant IBD– Ages 12-17 yrs. (average 15 yrs.), 3 M / 4 F– 4 UC, 2 CD, 1 IC– Related donor FMT via colonoscopy and f/u home
enemas
• All seven were recommended escalation of therapy– 85% (6/7) recommended Tacrolimus +/- surgical colectomy
• All 6 were steroid dependent at time of FMT– 15% (1/7) recommended addition of a biologic
Docktor M, et al. Unpublished data 2011-2013
Our experience: FMT for IBD“Innovative Therapy”
• 85% (6/7) stabilized and were weaned from steroids – 57% (4/7) improved but remained stable on previous
therapy– 28% (2/7) discontinued steroids, biologic and 6-MP
• 1 in deep clinical remission on 5-ASA & Vancomycin 2+ years
• 1 with mild activity, de-escalated to 5-ASA– 15% (1/7) continued to slowly worsen, Tac surgical
colectomy 9 months later
• No adverse events reported, all procedures and f/u well tolerated up to 2.5 years out.Docktor M, et al. Unpublished data 2011-2013
Microbial analysis of FMT
Docktor M, et al. Unpublished data 2011-2013
• 10 children with RCDI (1-19 years)
• Open label single, related FMT via NG tube (2) or colonoscope (8)
• 3/10 patients had concomitant IBD
• Overall success rate 90% for curing RCDI– 7/7 (100%) among non-IBD patients– 2/3 (66%) among IBD patients
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Russell GH, et al. JPGN. 2014; 58(5): 588-592.
Russell GH, et al. JPGN. 2014; 58(5): 588-592.
• 11 y/o M with CD • Counted as failure• Redeveloped CDI after re-
admission 2 months
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Russell GH, et al. JPGN. 2014; 58(5): 588-592.
Russell GH, et al. JPGN. 2014; 58(5): 588-592.
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• 19 y/o F with UC• Admitted for severe, acute colitis• 100% better for 5 days then severe
bloody diarrhea• Never redeveloped CDI• Potential fulminant UC flare
secondary to FMT?
Fecal Microbiota Transplantation in Children with Recurrent Clostridium difficile Infection
Anne Pierog, MD, Ali Mencin, MD, and Norelle Rizkalla Reilly, MDColumbia University Medical Center,
Division of Pediatric Gastroenterology, Hepatology and Nutrition
• 6 patients with RCDI – Ages 4-21 yrs., 4 M / 2 F– 1 CD, 1 IC – Related donor FMT via colonoscopy
• 100% cure rate for C. diff• 12 y/o M with CD
– Initial clinical improvement @ 1 week– Acute appendicitis @ 2 weeks post FMT– Clinical “remission” with optimized therapy @ 12 weeks
• Follow up: both IBD patients cured of CDI, required escalation of IBD therapy
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Pierog A, et al. Peds Infec Dis Journ. Accepted for publication.
FMT FOR PEDIATRIC ULCERATIVE COLITIS
• Safety and tolerability of FMT via enema in 9 children w/ UC
• 7 – 21 years, mild-moderate disease (PUCAI 15-65)• Daily enemas x 5 days
– 78% (7/9) showed clinical response within 1 week– 67% (6/9) maintained clinical response at 1 month – 33% (3/9) achieved clinical remission at 1 week
• FMT via enema was feasible and tolerable in children with limited side effects.
Kunde S, et al. JPGN 2013 Jun;56(6):597-601
Kunde S, et al. JPGN 2013 Jun;56(6):597-601
Fecal Microbial Transplant via Nasogastric tube for active
Pediatric Ulcerative Colitis David L. Suskind1 M.D., Namita Singh2 M.D., Heather Nielson,
Ghassan Wahbeh1 M.D.,
• Open label single FMT via NG tube• Four male patients, 14.5 ± 1.7 years• Pretreatment with Rifaximin TID x 3 days• Follow up @ 2, 6, 12 weeks
– Mild symptoms including vomiting and bloating– 2/4 developed C.diff within 4 months (1 recurrence)– No change in PUCAI, CRP, albumin, HCT
• Overall safe but not efficacious
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Suskind D, et al. JPGN. Accepted for publication.
FMT FOR PEDIATRIC CROHN’S DISEASE
Fecal Microbial Transplant Effect on Clinical Outcomes and Fecal Microbiome in Active
Crohn’s disease David L. Suskind MD1, Mitchell J. Brittnacher PhD2, Ghassan Wahbeh MD1, Michele L.
Shaffer PhD1, Hillary S. Hayden2, Namita Singh MD3, Christopher J. Damman MD4, Kyle R. Hager, Heather Nielson, Samuel I. Miller MD2,4,5,6
• Nine pediatric patients– Mild to moderate Crohn’s (PCDAI of 10-29) – 12-19 years– Open label NGT delivery of related donor FMT
• Studied– Clinical response (PCDAI, CRP, calprotectin)– Engraftment & % similarity to donor– Microbial changes
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Suskind DL, et al. Seattle Children’s Hospital. Data in submission for print.
Suskind DL, et al. Seattle Children’s Hospital. Data in submission for print.
Fecal Microbial Transplant Effect on Clinical Outcomes and Fecal Microbiome in Active
Crohn’s disease David L. Suskind MD1, Mitchell J. Brittnacher PhD2, Ghassan Wahbeh MD1, Michele L.
Shaffer PhD1, Hillary S. Hayden2, Namita Singh MD3, Christopher J. Damman MD4, Kyle R. Hager, Heather Nielson, Samuel I. Miller MD2,4,5,6
• 7/9 (78%) Had PCDAI fall < 10 @ 2 weeks– 2 required escalation of Rx
• 5/7 (71%) Remained < 10 @ 12 weeks
• No or modest improvement in patients without engraftment
• More divergent = better engraftment and response
Suskind DL, et al. Seattle Children’s Hospital. Data in submission for print.
Fecal Microbial Transplant Effect on Clinical Outcomes and Fecal Microbiome in Active
Crohn’s disease David L. Suskind MD1, Mitchell J. Brittnacher PhD2, Ghassan Wahbeh MD1, Michele L.
Shaffer PhD1, Hillary S. Hayden2, Namita Singh MD3, Christopher J. Damman MD4, Kyle R. Hager, Heather Nielson, Samuel I. Miller MD2,4,5,6
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Reci
pien
t Sim
ilarit
y to
don
or %
Suskind DL, et al. Seattle Children’s Hospital. Data in submission for print.
Fecal Microbial Transplant Effect on Clinical Outcomes and Fecal Microbiome in Active
Crohn’s disease David L. Suskind MD1, Mitchell J. Brittnacher PhD2, Ghassan Wahbeh MD1, Michele L.
Shaffer PhD1, Hillary S. Hayden2, Namita Singh MD3, Christopher J. Damman MD4, Kyle R. Hager, Heather Nielson, Samuel I. Miller MD2,4,5,6
Time relative to FMT (days)
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Engr
aftm
ent s
core
(% )
Suskind DL, et al. Seattle Children’s Hospital. Data in submission for print.
Time relative to FMT (days)
Fecal Microbial Transplant Effect on Clinical Outcomes and Fecal Microbiome in Active
Crohn’s disease David L. Suskind MD1, Mitchell J. Brittnacher PhD2, Ghassan Wahbeh MD1, Michele L.
Shaffer PhD1, Hillary S. Hayden2, Namita Singh MD3, Christopher J. Damman MD4, Kyle R. Hager, Heather Nielson, Samuel I. Miller MD2,4,5,6
Vandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
Fecal microbial transplantation in a one-year-old girl
with early onset colitis - caution advised
Vandenplas Y, Veereman G, van der Werff ten Bosch J, A. Goossens, Pierard D, Samsom JN, Escher JC
Vandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
Ever
y 2
wee
ks F
MT
From healthy age matched niece
7- 14 days of remission
Vandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
From older brother
Vandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
From older brother
FMT
FMT
FMT
Vandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
From older brother
FMT
FMT
FMT
Remission 1 month
Vandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
From older brother
FMT
FMT
FMT
Remission 1 month
Remission 2 month
2 m
onth
sVandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
From older brother
FMT
FMT
FMT
Remission 1 month
Remission 2 month
Remission 6 month2
mon
ths
2 m
onth
s
Clinical Trials
• NCT01096635 – DBPCT using FMT to treat chronic active UC (Padaramothy, New South Wales)
• NCT02049502 – FMT to treat active UC associated post-IPAA pouchitis (Shaffer, Emory)
• NCT0184717- FMT effect on the IBD microbiome (Moss, Beth Israel)
• NCT01947101 – FMT as a transition off immunosuppression with stable UC (Kellermeyer, Baylor)
Summary
• FMT appears safe and well tolerated in children independent of route
• Efficacious for RCDI• Mixed response in IBD– Best route ?– Pre-FMT antibiotics ?– Donor matching ? – Durability / maintenance ?
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The road ahead
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