Clinical Outcomes of Medications Post Anti-TNF: Researching Effectiveness in Pediatric IBD
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,100
- 试验地点
- 4
- 主要终点
- Change in Pediatric Ulcerative Colitis Activity Index (PUCAI) Score
研究概览
简要总结
The purpose of the study is to compare the clinical effectiveness and safety of newer inflammatory bowel disease (IBD) medications in anti-tumor necrosis factor (TNF) refractory patients with pediatric IBD (PIBD). Refractory means that there was no clinical response to anti-tumor necrosis factor (TNF) drugs or that the if there was a response, it is no longer present. The main question this study aims to answer is:
Are the newer medications used to treat IBD just as safe and effective for treating IBD in children.
Participants will already be taking these newer medications as assigned by their regular health care provider.Participants' care will be managed by their regular healthcare provider as part of usual (standard) care for those with PIBD. While taking these medications, participants will be asked to answer questions about their symptoms and health periodically over the course of the study.
详细描述
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). 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Children with Ulcerative Colitis (UC)
Pediatric UC patients initiating non-anti-TNF biologics and small molecules that are FDA-approved for adult populations
Children with Crohn's disease (CD)
Pediatric CD patients initiating non-anti-TNF biologics and small molecules that are FDA-approved for adult populations
Retrospective Safety Analysis
Retrospective cohort focused on the long-term safety of non-anti-TNF biologics and small molecules that are FDA-approved for adult populations in for CD and or UC. Electronic health record (EHR) data (retrospective cohort) will be collected from medical charts and EHRs at participating institutions.
结局指标
主要结局
Change in Pediatric Ulcerative Colitis Activity Index (PUCAI) Score
时间窗: Each clinic visit (baseline through follow-up, up to 3 years)
The Pediatric Ulcerative Colitis Index (PUCAI) is a patient-centered, 6-item measure assessing abdominal pain, stool characteristics, and patient functioning. Scores ranging from 0 - 85 with higher scores indicate more disease activity. A cut-point of \<10 indicates remission, ≥10 to 34 mild disease, ≥35-65 moderate disease, and ≥65 severe disease. Response is defined as a reduction of ≥ 20 points.
Measure of Crohn's disease (CD) impact on patients' daily lives (TUMMY CD)
时间窗: Baseline, months 2, 4, 6, 8, 10, 12, 18, 24, 30, 36
The TUMMY CD patient reported outcome (PRO) has been developed and is undergoing validation. For our CD cohort, we will collect data on both the TUMMY-CD and the PROMIS IBD PROs. If TUMMY-CD is proven to be a reliable and valid PRO by the time of our data analysis, we will utilize this as our primary PRO. Otherwise, we will rely on PROMIS IBD PROs. Change will be calculated as the difference between baseline and post-baseline scores, with higher scores reflecting greater symptom severity.
Measures of ulcerative colitis (UC) impact on patients' daily lives (TUMMY UC)
时间窗: Baseline, months 2, 4, 6, 8, 10, 12, 18, 24, 30, 36
Description: The TUMMY UC patient reported outcome (PRO) is a validated patient-reported outcome tool designed to assess gastrointestinal symptom burden in children and adolescents with ulcerative colitis (UC). Change will be calculated as the difference between baseline and post-baseline scores, with higher scores reflecting greater symptom severity. Scores range from 0 to 114 with higher values indicating greater symptom burden.
PROMIS Symptom Measure of Irritable Bowel Disease (IBD)
时间窗: Baseline, months 2, 4, 6, 8, 10, 12, 18, 24, 30, 36
NIH Patient Reported Outcome Measurement Information System (PROMIS) symptoms scale is a disease-specific PRO. Prior validation of the PROMIS IBD measure has demonstrated acceptable internal consistency (Cronbach's alpha of 0.74), as well as discriminative and known groups validity. The PROMIS IBD symptom score has been standardized such that a T score of 50 represents the median score in the reference pediatric IBD population. T scores range from 40 to 80 with higher scores indicating higher symptom burden and a minimal clinically important difference (MCID) of 5. We will not use the PROMIS IBD for measure of UC
Change in Pediatric PROMIS® Patient-Reported Outcome (PRO) Pain Interference Score for Crohn's Disease and Ulcerative Colitis (CD and UC)
时间窗: Baseline, months 6, 12, 18, 24, 30, 36
Pediatric Patient Reported Outcome Measurement Information System (PROMIS) assesses domains relevant to children and adolescents with CD and UC and their reported pain score. PROMIS Pediatric PROs domains have been standardized such that a T score of 50 represents the median score in the reference pediatric IBD population with higher scores indicating higher symptom burden and minimal clinically important difference (MCID) of 5.
Change in Pediatric PROMIS® Fatigue Score for Crohn's Disease and Ulcerative Colitis (CD and UC)
时间窗: Baseline, months 6, 12, 18, 24, 30, 36
Pediatric Patient Reported Outcome Measurement Information System (PROMIS) assesses domains relevant to children and adolescents with CD and UC and their reported fatigue score. PROMIS Pediatric PROs domains have been standardized such that a T score of 50 represents the median score in the reference pediatric IBD population with higher scores indicating higher symptom burden and minimal clinically important difference (MCID) of 5.
Change in Pediatric PROMIS® Anxiety Score for Crohn's Disease and Ulcerative Colitis (CD and UC)
时间窗: Baseline, months 6, 12, 18, 24, 30, 36
Pediatric Patient Reported Outcome Measurement Information System (PROMIS) assesses domains relevant to children and adolescents with CD and UC and their reported anxiety score. PROMIS Pediatric PROs domains have been standardized such that a T score of 50 represents the median score in the reference pediatric IBD population with higher scores indicating higher symptom burden and minimal clinically important difference (MCID) of 5.
Change in Pediatric PROMIS® Depression Score for Crohn's Disease and Ulcerative Colitis (CD and UC)
时间窗: Baseline, months 6, 12, 18, 24, 30, 36
Pediatric Patient Reported Outcome Measurement Information System (PROMIS) assesses domains relevant to children and adolescents with CD and UC and their reported depression score. PROMIS Pediatric PROs domains have been standardized such that a T score of 50 represents the median score in the reference pediatric IBD population with higher scores indicating higher symptom burden and minimal clinically important difference (MCID) of 5.
Change in sPCDAI Score for Crohn's Disease
时间窗: Each clinic visit (baseline through follow-up, up to 3 years)
The short Pediatric Crohn's Disease Activity Index (sPCDAI) is a validated tool to assess disease activity in children with Crohn's disease. It is based on clinical symptoms, physical examination findings, and laboratory values. Scores range from 0 to 90, with higher scores indicating greater disease activity. The outcome will be measured as the mean change in sPCDAI score from baseline to follow-up. T Scores ≤15 indicate remission, \> 15-29 mild disease and ≥30 indicate moderate to severe disease
次要结局
- Change in Fecal Calprotectin Concentration (CD and UC)(12 months after after taking prescribed medication for CD or UC)
- Number of Participants Experiencing Adverse Events (CD and UC)(After medication administration and every 3 months, up to 3 years)
- Proportion of Participants Experiencing Adverse Events (CD and UC)(After medication administration and every 3 months, up to 3 years)
- Exploration of Heterogeneity of Treatment Effects (HTE) Across Clinical Subgroups (CD and UC)(Baseline through follow -up for up to 3 years)