Clinical Outcomes of Medications Post Anti-Tnf: Researching Effectiveness in Pediatric Ibd
Effectiveness of Medications in Children with IBD After Anti-TNF Therapy
Steven Steiner, MD
Primary Investigator
Brief description of study
Over the past 10 years, new medication options have been approved for patients with IBD who did not respond to anti-TNF treatments. However, data is still limited for how these new medications work. This study may provide researchers with valuable information about the continued use of these medications. The purpose of this study is to compare the effectiveness and safety of these newer IBD medications. COMPARE is a multi-center, observational cohort study that includes both prospective and retrospective components and two patient population cohorts-Crohn's disease (CD) and ulcerative colitis (UC).
THIS STUDY IS ENROLLING BY INVITATION ONLY - Potential participants with CD and 550 with UC or IBD-U whose disease is refractory to anti-TNF therapy will be identified and contact by the research team about study participation.
Detailed description of study
The study will recruit pediatric IBD patients initiating non-anti-TNF biologics and small molecules that are FDA-approved for adult populations. The primary analyses in each cohort will compare the two most frequently used classes, with all IL-23 agents analyzed as a single class. Secondary comparisons will be conducted for any classes initiated by at least 50 participants. The investigators will also perform a retrospective cohort study using EHR data extracted from participating sites.
IL-23 agents could be any of the following medications:
- Vedolizumab (trade name Entyvio™)
- Ustekinumab (trade name Stelara™)
- Risankizumab (trade name Skyrizi™)
- Guselkumab (trade name Tremfya™)
- Mirikizumab (trade name Omvoh™)
- Tofacitinib (trade name Xeljanz™)
- Upadacitinib (trade name Rinvoq™)
While taking these medications, participants (or parent/caregiver proxies) will complete patient-reported outcome surveys (PROS) at baseline, every 2 months for the first 12 months, and every 6 months during the 2nd and 3rd years of follow-up. The surveys will collect information about the participants' general health and well-being while taking these medications.
Clinical follow-up will occur in the context of routine care (e.g., clinic visits, telehealth encounters) for a minimum of 1-year and up to 3 years after the index date, regardless of whether the participant remains on the index treatment. The study anticipates relatively standard follow-up for each participant, based on best clinical practice, while allowing for natural variation.
The study will collect data abstracted from the medical charts of enrolled participants. Baseline data, including potential confounders described in the statistical analysis plan, will be collected by sites upon participant enrollment or shortly thereafter. Follow-up data will be collected with each outpatient gastrointestinal (GI) visit, hospitalization, surgery, colonoscopy, imaging test (MRI, CT, intestinal ultrasound), laboratory test (unless electronically captured), IBD medication change, and adverse events.
In addition, structured electronic health record (EHR) data on enrolled participants will be extracted using automated queries utilizing the PCORnet® PCORnet Common Data Model (CDM) to supplement case report forms. EHR data extraction will include laboratory values, anthropometrics, emergency department (ED) visits (and diagnosis codes), hospitalizations (and diagnosis codes), antibiotic/antiviral prescriptions, encounter dates, and diagnosis codes for events of special interest (e.g., infections, malignancy, blood clots).
The study will collect and record adverse events from participants and their caregivers, as well as via regular EHR queries using the PCORnet® CDM.
Prospective enrollment is expected to take approximately 36 months with a minimum follow-up of 12 months for each participant (maximum of 36 months).While participating in this research, participants will continue to receive standard of care as directed by their regular health care provider. In addition, they will be asked to answer questions about symptoms and health periodically over the course of the study. Questions can be completed electronically on a smartphone, tablet, or computer and should take no more than 15 minutes to complete each time.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Inflammatory Bowel Disease, IBD, Crohns' Disease, Ulcerative Colitis, Riley
-
Age: 1 years - 18 years
-
Gender: All
Inclusion Criteria:
- Age < 18 years at study enrollment
- Diagnosis of CD, UC, or IBD-U by standard diagnostic criteria
- Prior non-response or loss of response to one or more anti-TNF agents
- Planning to initiate treatment with any of the following comparator agents: vedolizumab (α4β7 integrin antibody), ustekinumab (anti-IL-12/23 antibody), risankizumab, guselkumab, or mirikizumab, (IL-23 inhibitors), tofacitinib (JAK inhibitor), and upadacitinib (JAK inhibitor). Biosimilars or generic medications for any of the above will also be allowed and handled/analyzed in an identical manner to originators.
- Ability to provide child assent, if required per regulatory or local institutional guidelines, and parental informed consent in English or Spanish
Exclusion Criteria:
- Plans to change care to a different center within 1 year
- Prior use of a comparator agent (i.e., only patients starting their first comparator medication as monotherapy following anti-TNF will be eligible)
- Contraindication to any of the treatments under investigation
- Patients with UC or IBD-U who have undergone colectomy
- Patients with current ostomy
This study investigates the effectiveness and safety of newer medications for pediatric patients with Inflammatory Bowel Disease (IBD) who did not respond to anti-TNF treatments. Inflammatory Bowel Disease includes conditions like Crohn's disease (CD) and ulcerative colitis (UC), where the body's immune system attacks the digestive tract, causing inflammation. The purpose of this study is to observe how these newer medications perform in managing IBD symptoms.
Participants will continue with their regular care and answer questions about their health and symptoms during the study. These questions can be completed on a smartphone, tablet, or computer and take about 15 minutes each time. Participants may also choose to provide samples of stool, saliva, blood, and previously collected tissue during colonoscopies, although this is optional.
- Who can participate: Children diagnosed with Crohn's disease, ulcerative colitis, or IBD-unspecified who did not respond to anti-TNF treatments can participate. They must be starting an investigational medication like vedolizumab or ustekinumab and provide consent in English or Spanish.
- Study details: Participants will continue their usual care and complete health questionnaires electronically. They may provide optional samples like stool and blood. This study is observational, meaning it will not change their current treatment.
- Study timelines: The study will last up to 3 years.
