Miguel Regueiro, MD
Professor of Medicine
Chief of the Digestive Disease Institute
Cleveland Clinic, Ohio
By Miguel Regueiro, MD, with Marcus A. Banks
The first study in The Regueiro Report this month assesses the efficacy and safety of upadacitinib (Rinvoq, AbbVie) for people with perianal fistulizing Crohn’s disease. It’s a post hoc analysis of the phase 3 induction and maintenance trials U-EXCEL, U-EXCEED and U-ENDURE that led to upadacitinib’s approval for treating moderate to severe CD. One of the authors is a colleague of mine at Cleveland Clinic, in Ohio.
The new study focuses on perianal fistulizing disease, which is important given its prevalence rate of approximately 25% of CD patients in the United States (J Manag Care Spec Pharm 2024;30[5]:420-429). While fairly common, that prevalence is low enough to make it difficult to measure the direct impact of advanced therapies on healing perianal fistulas. The study was a post hoc review of clinical trial data including participants with and without fistulas at baseline to inform whether upadacitinib is an effective treatment for this disease.
The evidence is encouraging. Compared with placebo, upadacitinib led to higher resolution of fistula drainage during both induction and maintenance.
In my practice, if a patient with CD presents with perianal fistula and has not received advanced treatment, my preferred first-line therapy is infliximab (Remicade, Johnson & Johnson). To date, the only prospective trial for perianal fistula has been with infliximab, and we have years of experience with this medication.
That said, some people will be intolerant to infliximab or have an inadequate response. For these cases, upadacitinib could be a valuable second-line treatment, and I have had success with it in my own practice.
This month’s other article focuses on the psychological impact of inflammatory bowel disease. When treating IBD, our main focus is controlling inflammation, and most clinical trial end points are related to decreasing bowel inflammation. However, many of our patients have other symptoms that diminish their quality of life.
Sometimes, even after achieving remission, people with IBD report pain, fatigue and urgency, symptoms that can be present in the absence of inflammation and common in irritable bowel syndrome. We are now realizing that there is an overlap of IBD and IBS—both of which cause bowel symptoms and affect quality of life.
One valuable tool for people with IBD and IBS is cognitive behavioral therapy (CBT), in which a behavioral health specialist, such as a psychologist or licensed social worker, helps a patient reframe their thoughts and focus on alleviating bowel symptoms. This study suggests that offering CBT to people with IBD who are facing pain, fatigue and incontinence is valuable.
Patients with both IBS and IBD were more likely to experience depression, anxiety and negative perceptions of their symptoms than those with IBD alone. Practicing CBT may alleviate these psychological challenges in people with IBD who are in clinical remission but have IBS-type symptoms.
Providers at Cleveland Clinic’s IBD Center have found that focusing on the brain–gut connection with CBT and other behavioral healthcare interventions can be an effective part of a whole-person approach to patient care.
Upadacitinib for Perianal Fistulizing CD
Clin Gastroenterol Hepatol 2025;23(6):1019-1029
Of 1,021 participants in the U-EXCEL and U-EXCEED induction trials, 143 (14.0%) had a fistula at baseline and 128 of these fistulas were perianal (56 draining). Compared with placebo, any dose of upadacitinib led to improved clinical outcomes for the participants.
There was a statistically significant greater resolution of drainage of perianal fistulas at the end of induction (placebo, 5.6% [1/18]; upadacitinib 45 mg, 44.7% [17/38]; P=0.003). Resolution of drainage also was seen at the end of maintenance, but the results were not statistically significant: placebo, 0% (0/11); upadacitinib 15 mg, 28.6% (4/14); P=0.105; upadacitinib 30 mg, 23.1% (3/13); P=0.223.
In addition, after induction, closure of perianal fistula openings was achieved in 19 of 86 patients treated with 45 mg of upadacitinib (22.1%) and two of 42 given placebo (4.8%) (P=0.013). After maintenance, closure rates were achieved in six of 32 patients given 15 mg of upadacitinib (18.8%) (P=0.024), four of 25 patients given 30 mg of upadacitinib (16%) (P=0.037) and none of the 30 patients in the placebo group (0%).
Managing Modifiable Psychological Factors Associated With IBS-Type Symptoms in IBD
J Crohns Colitis 2025;19(5):jjae183
This study is an analysis of 780 participants in the IBD-BOOST clinical trial, which offered digital support for managing the psychological and behavioral impact of living with IBD. Many trial participants reported persistent fatigue, pain and fecal urgency/incontinence, all hallmarks of IBS, even when in clinical remission from IBD.
The investigators used multinomial logistic regression to determine contributors to these IBS-like symptoms. Depression, anxiety and negative symptom perception were some of the contributors to fatigue, pain and defecation challenges. All-or-nothing behaviors regarding activities such as eating or exercise, or avoiding social activities altogether, also made the cluster of IBS-like symptoms more likely.
This article is from the August 2025 print issue.