Clinical trial NCT02503514: Autoimmune Paradoxical Reactions in IBD Longitudinal Cohort
Official title: Autoimmune Paradoxical Reactions in IBD Longitudinal Cohort - APRIL Cohort
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inflammatory Bowel Diseases
Crohns Disease
Ulcerative Colitis
Colitis
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Crohn's and Colitis Foundation
First posted: 2015-07-21
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults with confirmed IBD on a biologic agent or with plans to initiate this within 1 month.

Brief summary: Purpose: Inflammatory bowel disease patients undergoing treatment with varying biologic agents will be evaluated for incidences of paradoxical immune reactions, the risk factors associated with those paradoxical immune reactions, and whether the paradoxical immune reactions and their associated risk factors differ based on formulation of biologic agent.

Participants: All adults (≥18 year) with confirmed IBD on a biologic agent or with plans to initiate treatment in 1 month

Procedures (methods): Subjects undergoing treatment with a biologic agent will be followed indefinitely for paradoxical immune reactions. Data will be collected at baseline as well as serum and plasma for banking. Subjects will be followed at 6 month intervals either via email, telephone interviews or at the time of clinic follow-up visits. In the event of a de-novo paradoxical reaction, specific information will be collected from sites in an event capture form, with data abstracted from routine clinical care for the paradoxical reaction. Subjects will continue to be followed every 3 months after the event via email, telephone contact to determine whether resolution and/or recurrence occurred, and to determine any changes in medical therapy. Serum and plasma will be re-collected at the time of first event for comparison to baseline samples and to samples from controls (those on biologics without study documented paradoxical immune reactions). At resolution of the event, patient will return to 6 month follow up schedule. Subjects can discontinue and/or fail a particular biologic treatment; therefore they will also be followed for paradoxical immune reactions, on any new biologic treatment they undergo while in the study.

Detailed description: Inclusion/Exclusion Criteria: All adults (≥18 year) with confirmed IBD on a biologic agent or with plans to initiate this within 1 month (defined as any anti-TNF, natalizumab, vedolizumab or ustekinumab) will be enrolled into a prospective cohort (initially in a pilot setting at 5 sites, later with full funding involving all sites of the CRA). Individuals with current biologic use will be included (i.e. prevalent users), with records collected as to time of initial biologic start, and prior specific formulations. Ideally, new initiators of biologic agents will be recruited at the visit where the decision is made to start a biologic agent. Those with a prior history of one of the 4 described paradoxical outcomes associated with a biologic agent will also be included as prevalent cases in order to increase the sample size, with appropriate clinical information collected per medical record. All data on prevalent cases will be entered historically prospective follow up with still occur to ensure that paradoxical reaction does not recur.

Exposures: Data will be collected at baseline including demographic and disease specific factors, concomitant medications, laboratory data, as well as serum and plasma for banking.

Follow up: Individuals will be followed at 6 month intervals either via email, telephone interviews or at the time of clinic follow-up visits. Data event forms for outcomes occurring at any point during follow up will be collected real-time in clinic, or if triggered by standard follow-up at 6 months.

Outcome of paradoxical immune reaction: Outcomes are defined as a) psoriaform skin lesion, b) drug-induced lupus c) demyelinating disorder or d) vasculitis. In the event of a de-novo paradoxical reaction, specific information will be collected from sites in an event capture form, with data abstracted from routine clinical care for the paradoxical reaction. Medical records will be obtained confirming the response, with copies of pathology (dermatologic biopsy)or radiology (MRI) reports when applicable. For specific event capture forms. Individuals will continue to be followed every 3 months after the outcome via telephone contact to determine whether resolution and/or recurrence occurred and changes in medical therapy. At resolution of the event, patient will return to 6 month follow up. Serum and plasma will also be re-collected at the time of first outcome in cases for exposure to baseline samples and to those of controls (those on biologics without paradoxical immune reaction). Serum and plasma will be collected at the time of event diagnosis, when possible (within 2 months). If not possible, blood draw can be "missed" in circumstances where patient is not seen in clinic in this window.

Timeline for study contacts:

The top timeline is for an individual who does not develop an event, baseline in-person consent and serum collection, contact every 6 months for telephone contact visit or follow up visit during the time of routine clinic follow-up. The bottom line is for someone who does develop an event, with closer follow-up until event resolution, and repeat serum collection. Contacts therefore range from 3-6 months, with the vast majority having follow up at 6 month intervals.

Eligibility criteria: Inclusion Criteria:

* Ability to understand and sign informed consent.
* Adults (male or female) with confirmed IBD diagnosed by routine clinical, radiographic, endoscopic and pathological criteria.
* Adults age 18 or older.
* Adults on a new biologic agent or with plans to initiate a biologic agent, within 1 month for the treatment of their IBD.

Exclusion Criteria:

* Inability to understand and sign informed consent.
* Inability to confirm diagnosis of IBD from medical records
* Inability to confirm time of initial biologic start, and prior specific formulations from medical records.

Primary outcomes:
measure: Number of Participants with specific paradoxical Adverse Events Using Biologic therapies as a part of routine care for the treatment of IBD
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill- CGIBD
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Millie D Long, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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