Originally published by our sister publication Gastroenterology & Endoscopy News
Chief of the Digestive
Disease Institute
Cleveland Clinic, Cleveland
By Miguel Regueiro, MD, with Marcus A. Banks
This month’s The Regueiro Report looks at two distinct issues: the viability of using fecal microbiota transplantation to treat active ulcerative colitis and evidence of additional benefits of upadacitinib (Rinvoq, AbbVie) for people with Crohn’s disease beyond the traditional outcomes of clinical response, remission and endoscopic improvement.
The etiology of UC is unknown but may stem from an alteration in the microbiome of the GI tract. This dysbiosis may lead to an immune-mediated response resulting in UC. Given the great benefit of FMT for treating Clostridioides difficile infection, it’s natural to explore whether this same approach can help in other conditions that affect the GI tract, such as UC.
However, the first article shows that FMT does not lead to steroid-free remission in people with moderate to severe UC. This was the primary end point of the study, and due to lack of efficacy, the study was ended. Based on these results, I would not recommend using FMT to treat people with UC.
I commend the authors for publishing this study, despite its negative result. It may seem easier to publish positive findings, but I think it is equally important to publish negative results. When researchers share negative results, the rest of us can learn from the experience, and the research informs future science.
The second study shows that upadacitinib can reduce fatigue while improving quality of life and work productivity in people with moderate to severe CD. All participants achieved a clinical response to once-daily 45-mg doses of upadacitinib during induction. In the maintenance phase, these other aspects of their lives also improved.
Our typical outcomes for medication efficacy are clinical response (as in this case), clinical remission and endoscopic improvement. It is my opinion that although these will remain primary outcomes, including patient-centered secondary outcomes such as fatigue and work productivity is important. I am hoping to see more and more studies include these outcomes.
Negative Results of FMT in UC
Clin Gastroenterol Hepatol 2024 May 23. doi:10.1016/j.cgh.2024.05.017
The RESTORE-UC study enrolled 72 people with moderate to severe UC (total Mayo score, 4-10), of whom 66 received either allogeneic FMT (n=30) or autologous FMT (n=36). There were no significant differences in baseline microbiome composition between the treatment arms. At week 8, only three participants in the allogeneic transplant arm and five in the autologous transplant arm reached the primary end point of steroid-free remission (P=0.72). At this point, after a pre-planned futility analysis, the researchers halted the study for futility.
Upadacitinib Improves Quality of Life in CD
J Crohns Colitis 2024 Jun 5. doi:10.1093/ecco-jcc/jjae083
In this study, patients who had a clinical response to 45 mg of upadacitinib taken once daily during the 12-week induction phase of the U-EXCEL and U-EXCEED trials went on to the 52-week maintenance U-ENDURE trial, in which they were randomized to receive daily upadacitinib doses of 30 or 15 mg, or placebo. All patients enrolled in the maintenance trial (n=502) had moderate to severe CD, and clinical response was defined as a reduction in stool frequency, abdominal pain or both.
The results of U-ENDURE showed that all gains in quality of life, fatigue and work productivity were sustained for 52 weeks in the clinical responders who continued to take upadacitinib. Compared with the clinical responders who began to receive a placebo during U-ENDURE, those in the treatment arms saw greater benefit in quality of life, fatigue and work productivity.