This is a Phase 3b, multicenter, open-label study to evaluate transmural healing and the disease modifying effect of guselkumab in participants aged 18 years or older, with active Crohn's disease. Eligible participants must be diagnosed with luminal Crohn's disease (confirmed by radiography, histology, and/or endoscopy) for a minimum of 3 months, have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or Advanced therapy (for example, biologic or jak inhibitor), or have medical contraindications to such therapies. Participants with active moderate‐to‐severe Crohn's disease will be enrolled in this study. About 112 participants will take part in this study worldwide at approximately 90 study sites. Participants will be in the study for about 104 weeks and will need to visit the study site approximately 28 times, this number may also vary depending on the study treatment group and whether the option of self-administration of the study drug at home at certain timepoints.

The goal is to see how well mirikizumab works for people with ulcerative colitis. This involves looking at its effects in their everyday lives. Understanding its real-world benefits helps determine how effective the medicine is outside of controlled clinical trials.

IBD affects over 1.5 million individuals in the US with an estimated direct cost of $6.1 billion. Recently, there has been an increased understanding of the importance of sleep and sleep disruption in IBD as a potential modifiable risk factor. The hypothesis is that intervening with morning bright light therapy (BLT) in IBD patients with CM will decrease intestinal permeability and pro-inflammatory cytokines, positively impact intestinal microbiota, and improve quality of life (QoL). A Re-Timer device will be used to administer BLT efficiently and safely to test this hypothesis. Prior to treatment subjects will be screened for subclinical inflammation using a validated questionnaire and fecal calprotectin level. They will also complete questionnaires about their dietary habits, fatigue, sleep habits, quality of life, and severity of their underlying disease. The subjects will be randomized and given BLT or the placebo non -BLT device for 4 weeks. The proposed studies will assess whether BLT has an impact on IBD patients' inflammation, intestinal permeability, and intestinal microbiota.

5-aminosalicylic acid (5-ASA) medications are first line treatment for mild to moderate Ulcerative Colitis (UC), comprise 81% of all UC prescriptions, and have a market share of 1.5 billion. However, despite 5-ASA frequency and optimization, 35% of patients fail induction therapy and 52% of patients fail to maintain remission at 12 months, requiring step up therapy to immunomodulators or biologics which have increased side effects and cost. This highlights a key challenge in UC which is to address the large inter- and intrapatient variabilities in both disease progression and variability in response to treatment. Chronotherapy is the timing of medical interventions according to the host circadian rhythms in order to optimize drug response and minimize toxicity, and is one explanation for the large variability in response to medications. The long-term objective of our research is to establish the hypothesis that is that appropriate time of day of administration of oral, once daily 5-ASA therapy in alignment with the host circadian rhythms will improve subclinical inflammation and microbial structure/function and increase mucosal 5-ASA levels. To test this hypothesis, In
response to the small R01 for pilot and feasibility clinical trials (PAS-20-160) and to test our hypothesis, we propose to conduct a six month, single center, randomized crossover pilot trial involving 60 subjects with inactive UC [Mayo score ≤2, endoscopic score 0-1] but subclinical inflammation [stool calprotectin > 50 mcg/g] on a stable dose of once daily 5-ASA medication. All subjects will be randomized to once daily 5-ASA medications two different times of the day: either between 06:00 – 10:00 h or 18:00 – 22:00 h. Three disease assessments will performed at: 1) enrollment just before randomization; 2) month 3, at the completion of first arm (condition 1), and 3) month 6, after completion of the second arm (condition 2). We will assess time impact of our chronotherapy protocol on: 1) subclinical inflammation (Aim 1): a) stool calprotectin; b) intestinal barrier integrity; and c) endoscopic/histology scores; 2) Microbiota: mucosal and stool microbiota structure and function (Aim 2); and 3) 5-ASA metabolism: a) increase mucosal levels of 5-ASA and b) mucosal NAT activity (Aim 3). In addition, optimal 5-ASA treatment (i.e., Aims 1-3) will depend upon host chronotype which will be monitored by validated questionnaires, rest-wake actigraphy, and urinary melatonin. The results of this innovative proposal will establish a key role for chronotherapy in the treatment of UC and provide pilot data for the future larger multicenter clinical trials. Chronotherapy will allow for a personalized medicine approach that incorporates circadian biology to improve efficacy and minimize intolerance in treatment of UC.

This research study is being conducted to gather information about patients with inflammatory bowel disease (IBD) to better understand their knowledge and preferences about self-help resources and learn how to help patients better manage their disease. Participation in this study will involve signing a research consent form, completing questionnaires, and the opportunity to participate in self-help resources. Some participants may be offered the opportunity to participate in a virtual focus group, as well. Participation in the study will last approximately 3 months.

The goal of this study is to collect health information from adults with IBD to better understand the disease and ultimately improve care for participants and other adults living with IBD. Participation in this study is voluntary. If a subject agrees to be in this study, we will collect information electronically (through a web-based platform called IBD Qorus) from the subject and the subject's IBD health care provider about their IBD health information.

Approximately 50 sites across the U.S. are currently participated in this study. The study is sponsored by the non-profit Crohn's and Colitis Foundation.

With the collected medical data, the study will focus on the strategy of identifying goals (or targets) of IBD care, developing a strategy to reach these goals, and then continuously evaluating progress of achieving these targets and modifying the treatment plan.