Hematopoietic Stem Cell Transplant followed by maintenance Vedolizumab

Crohn Disease

Autologous stem cell transplant

Days 1 and 2: Cyclophosphamide 2gm/m2/day x 2 days (total dose 4gm/m2) Day 3 until leukapheresis: G-CSF 10μg/kg/day to CD34+ >20x104/ml then leukapheresis daily to collection goal

Cyclophosphamide

Day -5 to -2: Cyclophosphamide 50 mg/kg/day (200 mg/kg total dose)

Day -3 to -1: 2.5 mg/kg/day (7.5 mg/kg total dose)

Thymoglobulin

Day -3 to -1: 1mg/kg prior to each ATG dose

Methylprednisolone

Starting first day after discharge from transplant admission, then 2 weeks after 1st infusion, 4 weeks after 2nd infusion, followed by every 8 weeks for 52 weeks (8 doses)

Vedolizumab

Icahn School of Medicine at Mount Sinai

Autologous Stem Cell Transplant for Crohn's Disease

Maintenance in Autologous Stem Cell Transplant for Crohn's Disease (MASCT - CD)

The proportion of patients in clinical remission, defined as a CDAI < 150, one year after autologous HCT from 45% to 65% as compared to baseline.

The change in endoscopic activity indices (SES CD) following autologous HCT and vedolizumab maintenance as compared to baseline.The maximal score for the SES-CD is 56. Each of 5 segments of intestine (rectum, colon - descending, colon - ascending, colon - transverse, ileum) is scored from 0-3 on four parameters - ulceration, extent of ulceration, extent of disease and stenosis. A maximal score of 45 is possible for the first three parameters and 11 for stenosis as a score of 3 implies a stricture that cannot be traversed prohibiting evaluation of later segments. An SES score of 0-2 would be defined as mucosal healing as the presence of a single ulcer in one bowel segment would necessitate a minimal score of 3. A decrease of SES of 50% from baseline is felt to represent an endoscopic response.

The change in overall burden of intestinal disease (Magnetic resonance enterography ((MRE)+SES-CD) following autologous HCT and vedolizumab maintenance as compared to baseline.

The change in quality of life indices as evaluated via the IBDQ following autologous HCT and vedolizumab maintenance as compared to baseline. An increase in the IBD-Q of 16-32 points is generally considered meaningful.

Amir Steinberg

Assistant Professor

Capsule endoscopy was ingested.The purpose was to detect patients with Crohn's Disease. Patients subsequently had standard ileocolonoscopy and small bowel follow through as comparison.

SB Capsule Then Standard Ileocolonoscopy

Sex: Female, Male

Region of Enrollment

To evaluate whether capsule endoscopy (CE) prior to ileocolonoscopy (IC) improves the diagnostic yield in patients with suspected Crohn's disease when compared to IC and SBFT. McNemar test was preformed in order to evaluate the diagnostic yield of IC combined with CE as compared to the diagnostic yield of IC combined with SBFT.

Ingestible capsule equipped with an endoscope with one imagers, before ileo-colonoscopy.

PillCam SB Followed by Ileo Colonoscopy

Following ingestible capsule, same patients also underwent ileo-colonoscopy (IC) and small bowel follow through (SBFT).

Small Bowel Follow Through (SBFT) and Ileo-colonoscopy

Diagnostic Yield in Suspected Crohn's Patients (CE Prior to IC vs. IC and SBFT)

McNemar test was preformed in order to evaluate the diagnostic yield of PillCam SB (CE) as compared to the diagnostic yield of small bowel follow through (SBFT).

Capsule endoscopy was ingested. The purpose was to detect patients with crohn's disease. Patients subsequently had standard ileocolonoscopy and small bowel follow through as comparison.

Pill Cam SB Capsule (CE)

Small Bowel Follow Through (SBFT)

Diagnostic Yield (CE vs. SBFT)

McNemar test was preformed in order to evaluate the diagnostic yield of PillCam SB (CE) as compared to the diagnostic yield of ileocolonoscopy (IC).

Capsule endoscopy was ingested.The purpose was to detect patients with crohn's disease. Patients subsequently had standard ileocolonoscopy and small bowel follow through as comparison.

PillCam SB Capsule

Standard Ileocolonoscopy (IC)

Diagnostic Yield (CE vs. IC)

Capsule endoscopy was ingested .The purpose was to detect patients with crohn Patients subsequently had standard ileocolonoscopy and small bowel follow through as comparison.

Overall Study

Director, Clinical Affairs

All subjects received both the capsule endoscopy procedure and the ileocolonoscopy procedure

Adverse Events

Crohn's Disease

Pillcam Platform with RAPID5 software and supporting SB2 capsules

Capsule Endoscopy

Mayo Clinic Arizona

Atlanta Gastroenterology

Stan Cohen

John Hopkins - Department of Medicine

UMass Memorial Medical Center

Minnesota Gastroenterology Associates

Private Practice

Thomas Jefferson University

McGill University Health Center

Rambam Medical Center

Malmo University Hospital UMAS

Evaluation of Capsule Endoscopy in Patients With Suspected Crohn's Disease

Medtronic - MITG

Subjects received double-blind (DB) 40 mg adalimumab subcutaneously (SC) every other week (eow) during the DB treatment period lasting 52 weeks.

Subjects received placebo subcutaneously (SC) every other week (eow) during the double-blind treatment period lasting 52 weeks.

Subjects received open-label (OL) 40 mg adalimumab subcutaneously (SC) every other week (eow) during the double-blind treatment period lasting 52 weeks.

Double-blind adalimumab 40 mg every other week

DB Adalimumab 40 mg Eow

Double-blind adalimumab placebo every other week

Placebo Eow

Open-label adalimumab 40 mg every other week

OL Adalimumab 40 mg Eow

Total

Clinical remission=Crohn's Disease (CD) Activity Index (CDAI) <150; number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI total score is >= 0 and without upper limit. Low score=less severe CD activity. Decrease indicates improvement.

Number of Participants Who Had Clinical Remission at Week 52 of Double-blind Treatment

Crohn's Disease Activity Index (CDAI) documents number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss during a 1-week assessment period. CDAI has a total score >= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.

Number of Participants Who Had Clinical Response-70 (CR-70; a Decrease in Crohn's Disease Activity Index of at Least 70 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment

Number of Participants Who Had Clinical Response-100 (CR-100; a Decrease in Crohn's Disease Activity Index of at Least 100 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 52 of Double-blind Treatment

Crohn's Disease Activity Index (CDAI) is a measure of disease severity. Number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI has a total score >= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.

Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment

Clinical remission=Crohn's Disease (CD) Activity Index (CDAI) <150; number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI total score is >= 0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.

Number of Participants Who Had Clinical Remission at Week 52 of Open-label Treatment

The International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score is an indicator of the activity of Crohn's disease. It measures absence (score of 0) or presence (score of 1) of abdominal pain, diarrhea or bloody stools more than 6 times per day, anal lesion, anal fistula, other complication, abdominal mass, weight loss, fever above 38 degrees Centigrade, abdominal tenderness, and blood pigment below 10 g/dL. Total possible score=0 to 10; low score=less disease activity. Decrease in score indicates alleviation of the disease; increase indicates aggravation of disease.

Change in International Organization for the Study of Inflammatory Bowel Disease (IOIBD) Score From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment

IBDQ is a validated disease-specific instrument that assesses the impact of IBD on patient quality of life during a 2-week recall period. It has 32 questions about bowel function and related symptoms, and their social and emotional impact. For each item, participants select 1 of 7 responses. 1=poor quality of life (e.g., feeling of fatigue "all of the time") and 7=good quality (e.g., feeling of fatigue "none of the time"). Scoring range = 32 to 224. Higher scores indicate better quality of life; increases in IBDQ = improved overall quality of life.

Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment

The Short-Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation of disease. The physical component reflects activity level, activity limitations, pain, and rating of one's health. Score on the physical component ranges from 0 (Poorest Health) to 100 (Best Health).

Change in Physical Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment

The Short-Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation. The mental component reflects energy/vitality, social functioning, limitations, and ratings of one's mental health. Score on mental component ranges from 0 (worst score) to 100 (best score).

Change in Mental Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 52 of Double-blind Treatment

Clinical remission = Crohn's Disease (CD) Activity Index (CDAI) <150; number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/aphthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI total score is >= 0 and without upper limit. Low score=less severe CD activity. Decrease indicates improvement.

All participants in this study who received at least 1 dose of adalimumab 40 mg every other week (double-blind or open-label).

Any Adalimumab

Number of Participants Who Had Clinical Remission at Week 148

Number of Participants Who Had Clinical Response-70 (CR-70; a Decrease in Crohn's Disease Activity Index of at Least 70 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 148

Number of Participants Who Had Clinical Response-100 (CR-100; a Decrease in Crohn's Disease Activity Index of at Least 100 Points From Lead-in Study [NCT00445939] Baseline Score) at Week 148

Crohn's Disease Activity Index (CDAI) is a measure of disease severity. Number of soft stools, abdominal pain, general well-being, presence of 6 signs (arthritis/arthralgia; iritis/uveitis; erythema nodosum/pyoderma gangrenosum/apthous stomatitis; fissure, abscess, anal fistula; other cutaneous fistula; fever over 100 degrees), taking medication for diarrhea, abdominal mass, hematocrit, and weight loss are documented during 1-week assessment period. CDAI has a total score >=0 and without upper limit. Low score=less severe CD activity. Decrease in score indicates improvement.

Change in Crohn's Disease Activity Index From Baseline of Lead-in Study (NCT00445939) to Week 148

Change in International Organization for the Study of Inflammatory Bowel Disease (IOIBD) Score From Baseline of Lead-in Study (NCT00445939) to Week 148

IBDQ is a validated disease-specific instrument that assesses the impact of IBD on patient quality of life during a 2-week recall period with 32 questions about bowel function and related symptoms & their social/emotional impact. Per item, participants select 1 of 7 responses (1=poor quality of life [e.g., feeling of fatigue "all of the time"]; 7=good quality [e.g., feeling of fatigue "none of the time"]). Scoring range=32 to 224. Higher scores indicate better quality of life; increases in IBDQ=improved overall quality of life.

Change in Inflammatory Bowel Disease Questionnaire (IBDQ) From Baseline of Lead-in Study (NCT00445939) to Week 148

The Short Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation of disease. The physical component reflects activity level, activity limitations, pain, and rating of one's health. Score on the physical component ranges from 0 to 100, with 0=Poorest Health and 100=Best Health.

Change in Physical Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 148

The Short Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 indicates alleviation of the disease and a decrease in score indicates aggravation. The mental component reflects energy/vitality, social functioning, limitations, and ratings of one's mental health. Score on mental component ranges from 0 (worst score) to 100 (best score).

Change in Mental Component of the Short Form-36 Health Survey From Baseline of the Lead-in Study (NCT00445939) to Week 148

All participants in NCT00445432 (Study M06-837) who received at least 1 dose of adalimumab 40 mg every other week (double-blind or open-label).

Through Week 52 of NCT00445432 (M06-837)

148 Weeks of Adalimumab Treatment

Global Medical Services

Subcutaneous injection of 40 mg adalimumab (0.8 mL/injection) every other week (eow)

adalimumab

Subcutaneous injection of placebo (0.8 mL/injection) every other week (eow)

Placebo

Site Ref # / Investigator 46965

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A Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn's Disease

A Multi-Center, Randomized, Double-blind, Placebo-controlled Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn's Disease

erythema nodosum/diarrhea

Autologous Stem Cell Transplant for Crohn's Disease

Evaluation of Capsule Endoscopy in Patients With Suspected Crohn's Disease

A Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn's Disease

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