2 months

Report
FMT in Pediatric IBD
Michael Docktor, MD
Boston Children’s Hospital
August 16, 2014
Disclosures
• I have no relevant disclosures or financial
obligations
2
Outline
I. Brief background
II. Anecdotal experience at Boston
Children’s
III. Oh and by the way, they have IBD
IV. Pediatric FMT in ulcerative colitis
V. Pediatric FMT in Crohn’s disease
VI. Future directions
3
Kostic, et al. Gastro. 2014; 146(5): 1489-149
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
Docktor
et al. Unpublished data 2011-201
– 15% (1/7) recommended addition
of a M,
biologic
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
Docktor M, et al. Unpublished data 2011-201
tolerated up to 2.5 years out.
Microbial analysis of FMT
Firmicutes
Post-FMT
(48 Days)
Post-FMT
(3 Days)
Donor
Pre-FMT
OTU Log Abundance
(Fraction of all reads)
0
1
2
3
4
5
Shannon Diversity
(Log-Scale)
Docktor M, et al. Unpublished data 2011-201
• 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
Russell GH, et al. JPGN. 2014; 58(5): 5888
Russell GH, et al. JPGN. 2014; 58(5): 588-
•
•
•
11 y/o M with CD
Counted as failure
Redeveloped CDI after readmission 2 months
Russell GH, et al. JPGN. 2014; 58(5): 58810
•
•
•
•
•
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?
Russell GH, et al. JPGN. 2014; 58(5): 58811
Fecal Microbiota Transplantation in Children with
Recurrent Clostridium difficile Infection
Anne Pierog, MD, Ali Mencin, MD, and Norelle Rizkalla Reilly, MD
Columbia 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 therapyPierog A, et al. Peds Infec Dis Journ. Accepted for publi
12
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
Kunde S, et al. JPGN 2013 Jun;56(6):597with limited side effects.
601
Kunde S, et al. JPGN 2013 Jun;56(6):597601
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
Suskind D, et al. JPGN. Accepted for publicat
16
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
Suskind DL, et al. Seattle Children’s Hospital. Data in submission for
18
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
Suskind DL, et al. Seattle Children’s Hospital. Data in submission for
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
Fecal Microbial Transplant Effect on Clinical Outcomes
and Fecal Microbiome in Active Crohn’s disease
Recipient Similarity to donor %
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)
Suskind DL, et al. Seattle Children’s Hospital. Data in submission for
21
Fecal Microbial Transplant Effect on Clinical Outcomes
and Fecal Microbiome in Active Crohn’s disease
Engraftment score (% )
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)
Suskind DL, et al. Seattle Children’s Hospital. Data in submission for
22
Fecal microbial transplantation in a one-yearold 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.
Vandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
Every 2 weeks FMT
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.
FMT
From older brother
FMT
FMT
Vandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
FMT
Remission 1 month
FMT
From older brother
FMT
Vandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
FMT
2 months
Remission 1 month
FMT
From older brother
Remission 2 month
FMT
Vandenplas Y, et al. JPGN. 10.1097/MPG.0000000000000281.
2 months
FMT
Remission 1 month
FMT
From older brother
FMT
2 months
Remission 2 month
Remission 6 month
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 ?
32
The road ahead
33

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