Upadacitinib Is Safe and Effective for Crohn's Disease: Real-World Data from a Tertiary Center.

Upadacitinib is a selective JAK-1 inhibitor approved for the treatment of rheumatoid arthritis and more recently, ulcerative colitis. Phase II trials demonstrated that upadacitinib induces endoscopic remission in patients with moderate-to-severe Crohn's disease. However, real-world data are lacking. We present a short report on our experience with off-label upadacitinib in patients with CD at a tertiary center. In this cohort of medically refractory patients with CD, treatment with upadacitinib resulted in subjective and objective responses in 25 and 42% of patients, respectively. Even at doses that are considered lower than currently being studied for CD, upadacitinib was associated with a favorable benefit-to-risk profile.

Endo-histologic Normalization Is Achievable with Tofacitinib and Is Associated with Improved Clinical Outcomes.

BACKGROUND: Recent real-world effectiveness studies investigating tofacitinib have been encouraging. Questions remain regarding the long-term effectiveness and safety of tofacitinib, effect on endoscopic remission rates, histologic changes, and alterations in fecal calprotectin levels. METHODS: This retrospective study includes consecutive patients with inflammatory bowel disease (IBD) who initiated tofacitinib therapy. We reviewed electronic medical records for demographic and clinical data, as well as all adverse events and hospitalizations. All patients receiving tofacitinib were included in the safety analysis and only patients with ulcerative colitis (UC) were included in the effectiveness analysis. RESULTS: 119 patients with IBD (97 UC, 12 CD, and 10 pouchitis) seen at our center between 2014 and 2020 were included in this study. Median follow-up was 32 weeks (interquartile range (IQR) 3-252). Clinical response and remission were observed in 70% and 21%, 59% and 33%, and 49%, and 37% at weeks 8, 24, and 52, respectively. Endo-histologic healing was achieved by 11%, 25%, and 37.5% of patients at weeks 8, 24, and 52, respectively. Histologic normalization occurred as early as 24 weeks in this cohort and was achieved by 26% of patients in endoscopic remission. Overall, there were 27 (25%) adverse events with 6 (5%) resulting in treatment discontinuation. There were 11 (10%) infections, none required treatment discontinuation. Ten (10.3%) patients underwent colectomy during the follow-up period. There were no cardiovascular adverse events in the cohort during follow-up. CONCLUSION: This study demonstrates the effectiveness and long-term safety of tofacitinib in patients with UC. Importantly, we show that the endpoint of endo-histologic healing is achievable with tofacitinib and can occur as early as week 8 of therapy.

Assessment of Comorbid Depression and Anxiety in Inflammatory Bowel Disease Using Adaptive Testing Technology.

BACKGROUND: Depression and anxiety are comorbidities of inflammatory bowel disease (IBD), and it is now recommended to screen IBD patients for these conditions. We screened patients using a novel computerized adaptive testing technology and compared the screening results to measures of disease activity. METHODS: Consecutive patients at our tertiary IBD clinic were asked to complete the validated CAT-MH™ survey (Adaptive Testing Technologies, Chicago, IL); we then reviewed disease and patient characteristics. Clinical remission status was determined based on clinical, laboratory, endoscopy and imaging results. Statistical methods included Fisher's exact test and Pearson Chi-square tests to assess association. Univariable and multivariable analyses were performed. RESULTS: We included 134 patients, of which 34 (25.3%) screened positive for depression and 18 (13.4%) screened positive for anxiety. We identified 19 (55.9 %) and 10 (55.5%) patients who were previously undiagnosed for depression and anxiety, respectively. Patients in clinical remission were less likely to screen positive for depression (OR 0.19; 95%CI 0.07-0.50) and for anxiety (OR 0.30; 95%CI 0.10-0.91). Compared to patients with negative CRP values, patients with positive CRP were more likely to also screen positive for depression (p=0.025) and anxiety (p=0.15). CONCLUSIONS: We demonstrate the utility of a novel testing technology for screening patients with IBD for depression and anxiety. We found a large number of patients with previously undiagnosed anxiety or depression and a significant positive association between clinically active IBD and these mental health conditions. This work supports and informs recommendations for mental health screening in the IBD population.

Clinical and Translational Considerations for Understanding Depression and Anxiety in Patients with Inflammatory Bowel Disease.

Depression and anxiety are comorbidities of inflammatory bowel disease (IBD). Though previous studies have proposed a relationship between anxiety, depression, and IBD, causality and directionality are largely unknown. Current and future research in these areas is aimed at exploring the biological underpinnings of this relationship, specifically pertaining to small molecule metabolism, such as tryptophan. Tryptophan is acquired through the diet and is the precursor to several vital bioactive metabolites including the hormone melatonin, the neurotransmitter serotonin, and vitamin B3. In this review, we discuss previous findings relating mental health comorbidities with IBD and underline ongoing research of tryptophan catabolite analysis.