Crohn's disease and ulcerative colitis affect about 1.6 to 3 million people in the United States with many of those being young children and adolescents. Physicians need better ways to inform decisions on therapy selection and recognize ongoing intestinal injury while on treatment. The main reason for this research study is to see if a blood test or stool test, which measures specific proteins, taken just before starting a new treatment for Crohn's disease can predict a patient's ability to achieve complete intestinal healing. The investigators also want to see if the intensity of gut inflammation can be detected by measuring a separate set of proteins in the blood.
Despite the heterogeneity of CD phenotypes and a potentially aggressive course of inadequately treated CD, treatment selection for newly diagnosed patients is currently based on clinical factors which do not define CD sub-types. Now, with additional biologic therapies for CD, there is a critical need for individual biochemical analysis both pre-treatment, and following induction to assess the probability of durable remission. These data will inform decisions on continued dosing of the current biologic, or whether addition of combination therapy or switching to a therapy with an alternative mechanism of action will be more beneficial. The Food \& Drug Administration (FDA) defines a companion diagnostic as a device that can identify patients most likely to benefit from a therapy or a device to monitor response with the purpose to adjust the treatment to achieve improved effectiveness.Our global aim is to develop a companion diagnostic (peripheral blood panel) that accurately predicts the probability of deep remission (clinical remission with MH) to anti-TNF and a protein (blood) biomarker panel that reproducibly distinguishes endoscopic MH from active (ulcerated) intestinal inflammation in patients with CD. The long-term strategy is to utilize the "low-risk" anti-TNF specific module (protein panel) to personalize CD therapy. With the addition of new biologics for CD, patients with a low-risk inflammatory profile would not only be expected to achieve MH but also predicted to respond to treatment escalation strategies while avoiding or stopping the drug (if drug exposure is optimized) sooner in patients in which the protein profile predicts a low probability of deep remission with anti-TNF. As additional therapies are approved for pediatric CD, the priority would be to avoid anti-TNF in patients with a "high-risk" protein profile and specifically select therapies that target the patient's individual inflammatory signature. Additionally, the investigators expect the protein profile of patients failing to achieve deep remission to provide further insight into molecular mechanisms contributing to the continued inflammation and thereby directing the next therapeutic option.
Study Type
OBSERVATIONAL
Enrollment
239
No standard dosing regimen will be used and the dose will be determined by the treating physician
No standard dosing regimen will be used and the dose will be determined by the treating physician
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Sustained Deep Remission
Sustained Deep Remission, defined as meeting all of the following at 1 year (check all that apply): * no wPCDAI score of ≥12.5 on two consecutive visits between week 30-52 * wPCDAI at week 52 is \<12.5 * off prednisone between weeks 30-52 * endoscopic remission (SES-CD\<3)
Time frame: 1 year
End of Induction Outcomes: Clinical Response
Improvement of \>17.5 points from baseline wPCDAI and/or Week 16 wPCDAI= \<12.5 points
Time frame: Week 16
End of Induction Outcomes: Clinical Remission
wPCDAI \<12.5 at Week 16
Time frame: Week 16
End of Induction Outcomes: Steroid Free Clinical Remission
wPCDAI \<12.5 and off prednisone by Week 16
Time frame: Week 16
End of Induction Outcomes: Fecal Biochemical Response
Fecal calprotectin improved \>50% from baseline stool (+/- 30 days from Week 16)
Time frame: Week 16
End of Induction Outcomes: Fecal Biochemical Remission
Fecal calprotectin \<250µg/g at Week 16 (+/- 30 days)
Time frame: Week 16
End of Induction Outcomes: Blood CRP Biochemical Remission
CRP \<0.5 mg/dL at Week 16
Time frame: Week 16
End of Induction Outcomes: Blood CD64 Biochemical Remission
nCD64 \<4.5 at Week 16
Time frame: Week 16
Week 52 Outcomes: Endoscopic Response
50% reduction in SES-CD score from baseline SES-CD (if performed)
Time frame: 1 year
Week 52 Outcomes: Endoscopic Remission
SES-CD \<3
Time frame: 1 year
Week 52 Outcomes: Minimal Endoscopic Activity
SES-CD \<6 with no individual SES-CD subscore \>1
Time frame: 1 year
Week 52 Outcomes: Complete Intestinal Healing
SES-CD = 0
Time frame: 1 year
Week 52 Outcomes: Sustained, Steroid-free Clinical Remission
wPCDAI \<12.5 for all visits from weeks 30-52, off prednisone
Time frame: 1 year
Week 52 Outcomes: Clinical Remission
wPCDAI \<12.5 and off prednisone at last study visit
Time frame: 1 year
Week 52 Outcomes: Clinical Remission and Endoscopic Response
wPCDAI \<12.5 at week 52 and SES-CD\>50% reduction from baseline
Time frame: 1 year
Week 52 Outcomes: Clinical Remission and Minimal Endoscopic Activity
wPCDAI \<12.5 at week 52 and SES-CD\<6 with no individual SES-CD subscore \>1
Time frame: 1 year
Week 52 Outcomes: Treatment Response
continues on anti-TNF without surgery, hospitalization and off prednisone by week 16
Time frame: 1 year
Week 52 Outcomes: Transmural ileal healing
ileum subscore stage 0 (score = 0) or stage 1 (score 1-3)
Time frame: 1 year
Week 52 Outcomes: Transmural colonic healing
all segments of colon subscore stage 0 (score=0) or stage 1 (score 1-3)
Time frame: 1 year
Week 52 Outcomes: Total Bowel Transmural healing
total ileum and colonic subscore is not greater than stage 1 on either individual score
Time frame: 1 year
Week 52 Outcomes: Fecal Biochemical Remission
fecal calprotectin \<250 µg/g at week 52
Time frame: 1 year
Week 52 Outcomes: Deep Fecal Biochemical Remission
fecal calprotectin \<150 µg/g at week 52
Time frame: 1 year
Week 52 Outcomes: CRP Biochemical Remission
CRP \<0.5 mg/dL at week 52
Time frame: 1 year
Week 52 Outcomes: CD64 Biochemical Remission
nCD64 \<4.5 at week 52
Time frame: 1 year
Week 52 Outcomes: PGA Remission
physician-rated PGA is quiescent and subject is off prednisone
Time frame: 1 year
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