Tofacitinib as Monotherapy Following Mesalamine Withdrawal in Ulcerative Colitis Patients in Sustained Remission: TOMO Phase 4 Randomised Study

Presenter: Behl N.

This phase 4, open-label randomized study evaluated whether mesalamine could be safely discontinued in patients with ulcerative colitis (UC) who were in sustained remission on tofacitinib 5 mg twice daily. A total of 69 patients with UC in clinical remission for at least 24 months on stable tofacitinib and mesalamine therapy were randomized to either tofacitinib monotherapy (n=35) or continued tofacitinib plus mesalamine (n=34) for 12 months. Clinical remission was maintained at both 6 and 12 months in most patients in both groups, with no clinically meaningful differences between treatment strategies. Only one patient in the monotherapy group experienced a mild symptomatic flare, while no relapses were reported in the combination therapy group.

C-reactive protein (CRP), fecal calprotectin, and Physician Global Assessment remained stable and comparable between groups throughout the study. Safety outcomes and adverse event rates were also similar, with no new safety signals observed.

These findings suggest that mesalamine withdrawal may be feasible in patients with UC who are in sustained remission on tofacitinib without compromising remission maintenance.

Comparative Effectiveness of Tofacitinib and Upadacitinib for Patients with Acute Severe Ulcerative Colitis: A Multi-Center United States Experience

Presenter: Wilcox S.

This retrospective multicentre cohort study compared colectomy outcomes in patients with acute severe ulcerative colitis (ASUC) treated with intravenous corticosteroids plus either tofacitinib or upadacitinib. The study included 208 patients admitted with ASUC, including 99 treated with tofacitinib and 109 treated with upadacitinib. Standard dosing was used in 60% of patients, while 40% received high-intensity dosing regimens. At 90 days, colectomy rates were similar between the tofacitinib and upadacitinib groups (22% vs 19%). Colectomy rates were also comparable between standard-dose and high-intensity treatment groups (23% vs 19%).

Inverse probability weighting analysis showed no significant difference in 90-day colectomy risk between tofacitinib and upadacitinib (adjusted hazard ratio [aHR]: 1.36; 95% confidence interval [CI]: 0.7–2.64; p=0.354). Similarly, no significant difference was observed between standard and high-intensity dosing strategies (aHR: 1.0; 95% CI: 0.45–2.21; p=0.942).

Overall, both JAK inhibitors demonstrated comparable short-term colectomy outcomes, although residual confounding cannot be excluded.

Real-World Comparative Effectiveness and Safety of Upadacitinib Versus Risankizumab for Ulcerative Colitis

Presenter: Dalal R.

This retrospective cohort study compared the real-world effectiveness and safety of upadacitinib (UPA) and risankizumab (RISA) in patients with active ulcerative colitis (UC). A total of 161 patients were included, with 100 receiving UPA and 61 receiving RISA. Baseline characteristics were generally similar, although patients treated with UPA had more prior anti-tumor necrosis factor (anti-TNF) exposure and higher baseline disease activity scores. After inverse probability of treatment weighting adjustment, UPA was associated with significantly higher odds of steroid-free clinical remission (SFCR) compared with RISA at both 12 weeks (odds ratio [OR]: 4.4; 95% confidence interval [CI]: 2.1–8.9) and 52 weeks (OR: 4.7; 95% CI: 2.0–10.6). Sensitivity analyses showed similar findings.

No significant differences were observed between UPA and RISA for endoscopic response (OR: 1.9; 95% CI: 0.6–5.8), endoscopic remission (OR: 1.5; 95% CI: 0.5–4.3), or treatment persistence through 52 weeks. Adverse events were reported more frequently with UPA than with RISA. The most common adverse events with UPA included infections, dermatologic conditions such as acneiform reactions, and metabolic abnormalities including dyslipidemia. One death occurred in each treatment group during follow-up.

Overall, UPA was associated with higher rates of steroid-free clinical remission compared with RISA, although adverse events were more common with UPA treatment.

Comparison of Effectiveness between Ustekinumab and Upadacitinib in Patients with Ulcerative Colitis Previously Exposed to at least One Anti-TNF Agent: Results from the Real-World Evidence Multicenter Uppercut Study.

Presenter: Buisson A.

This multicentre retrospective study compared the effectiveness of ustekinumab (UST) and upadacitinib (UPA) in patients with ulcerative colitis (UC) previously exposed to at least one anti-tumor necrosis factor (anti-TNF) therapy. A total of 226 patients were included, with 165 receiving UST and 61 receiving UPA. Patients in the UPA group had higher prior exposure to more than two biologics compared with the UST group (82.0% vs 46.6%). After propensity score adjustment, corticosteroid-free symptomatic remission at week 16 was similar between UST and UPA (35.1% vs 37.2%; p=0.91). Clinical remission, histological and endoscopic improvement, treatment discontinuation, UC-related hospitalization, and colectomy rates were also comparable between groups. However, subgroup analyses showed that UPA was significantly more effective than UST in patients previously exposed to at least two advanced therapies (OR=6.05; p=0.039) and in patients with primary failure to at least two prior biologics (OR=4.25; p=0.035).

Factors associated with lack of corticosteroid-free remission with UST included failure of at least three biologics and primary failure to at least one biologic.

Overall, UST and UPA showed comparable effectiveness in the overall anti-TNF-exposed UC population, although UPA demonstrated greater benefit in more heavily treatment-experienced patients.

Comparative Effectiveness and Safety of Three JAK Inhibitors-Filgotinib, Tofacitinib, and Upadacitinib-In Patients with Ulcerative Colitis: A Multicenter Real-World Study in Japan

Presenter: Sakatani A.

This multicentre retrospective study from Japan compared the real-world effectiveness and safety of the Janus kinase (JAK) inhibitors filgotinib, tofacitinib, and upadacitinib in patients with ulcerative colitis (UC). The study included 115 patients treated with filgotinib, 95 with tofacitinib, and 90 with upadacitinib. Patients receiving tofacitinib and upadacitinib had more active disease and greater prior exposure to biologics or JAK inhibitors compared with the filgotinib group. At week 8, clinical remission rates were significantly higher with upadacitinib (65.8%) compared with filgotinib (44.4%) and tofacitinib (37.9%) (p=0.00093). After adjustment for baseline differences, upadacitinib remained associated with significantly higher odds of remission versus filgotinib (adjusted OR: 2.94; 95% CI: 1.47–5.88) and tofacitinib (adjusted OR: 3.23; 95% CI: 1.67–6.25).

Similar trends were observed at week 24, although remission rates at week 52 were comparable between groups. Adverse events, including infections such as herpes zoster, hematologic abnormalities, liver enzyme elevations, and increases in creatine phosphokinase or cholesterol levels, were generally similar across all three treatments, with no new safety signals identified.

Overall, upadacitinib demonstrated higher short-term remission rates, while long-term effectiveness and safety were similar among the three JAK inhibitors.

Elevation of Liver Enzymes in Patients with Inflammatory Bowel Disease Treated with Upadacitinib is Associated with BMI

Presenter: Klein J.

This retrospective real-world study evaluated liver enzyme changes and metabolic risk factors in 200 patients with inflammatory bowel disease (IBD) treated with upadacitinib (UPA) between 2021 and 2024. The cohort included patients with ulcerative colitis (55%) and Crohn’s disease (36%), with a median age of 37 years and 47.5% female patients. Metabolic comorbidities included hypertension (20%), dyslipidemia (25%), metabolic dysfunction-associated steatotic liver disease (MASLD) (15.5%), and type 2 diabetes (6%). New alanine aminotransferase (ALT) elevation within 12 weeks of UPA initiation occurred in 16.3% of patients. Longitudinal analysis showed significant changes over time in ALT, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin levels.

In univariable analysis, ALT elevation was associated with higher body mass index (BMI), diabetes, and hypertension. In multivariable analysis, BMI remained an independent predictor of ALT elevation, with each 1 kg/m² increase associated with a 7% increase in risk (adjusted OR: 1.07; 95% CI: 1.00–1.14; p=0.04). Diabetes showed a borderline association, while MASLD, age, sex, alcohol use, and hypertension were not significant predictors.

Overall, early ALT elevation during UPA therapy was relatively common and appeared to be associated more strongly with BMI than with underlying liver disease or IBD type.

Real-World Effectiveness and Safety of Etrasimod in Ulcerative Colitis: Interim Analysis of the Effect-UC Study

Presenter: Irving P.

This interim analysis from the ongoing prospective EFFECT-UC study evaluated the real-world effectiveness and safety of etrasimod in patients with moderately to severely active ulcerative colitis (UC). A total of 121 patients from the United Kingdom, Germany, and Canada were included. The mean age was 40.2 years, and 60.3% of patients were biologic or Janus kinase inhibitor (JAKI)-naïve. Among patients with available week 12 data (N=63), symptomatic remission was achieved in 49.2%, while 77.8% achieved patient-reported outcome 2 (PRO2) response. Improvements in stool frequency, rectal bleeding, and bowel urgency were observed as early as week 2. In the safety analysis (N=122), treatment-emergent adverse events occurred in 46.7% of patients. Serious adverse events were reported in 4.1% and included ulcerative colitis flare, proctocolectomy, syncope, and gastrointestinal infections. All serious adverse events were considered unrelated to etrasimod by treating physicians.

Overall, etrasimod demonstrated clinically meaningful effectiveness up to 24 weeks in this interim analysis with no new safety signals identified.

Therapeutic Drug Monitoring of Upadacitinib for Inflammatory Bowel Disease Patients: A Real-World Prospective Observational Study

Presenter: Chen Y.

This prospective real-world study evaluated serum upadacitinib concentrations and the utility of therapeutic drug monitoring (TDM) in patients with inflammatory bowel disease (IBD). Eighteen patients contributed 75 serum measurements over 18 months. Most patients had ulcerative colitis (15/18), and 72.2% had prior biologic failure. Upadacitinib was used as monotherapy in 58.7% of assessments. Clinical remission was observed in 58 of 61 ulcerative colitis assessments and 10 of 14 Crohn’s disease assessments. The median serum upadacitinib concentration was 0.35 ng/mL, and concentrations increased significantly with higher doses. Drug levels were negatively correlated with dosing-to-sampling interval, indicating dose- and time-dependent pharmacokinetics (p<0.05).

Serum concentrations were not associated with albumin, age, sex, body mass index (BMI), prior biologic exposure, disease phenotype, or combination therapy. Two patients developed undetectable drug levels after previously detectable levels, suggesting poor adherence. Drug levels became detectable again after adherence counseling, and one patient regained biochemical and endoscopic remission after adherence improved.

Overall, the study suggests that therapeutic drug monitoring may help assess adherence and support maintenance of treatment efficacy with upadacitinib in clinical practice.

Efficacy and Safety of Upadacitinib after 5 Years of Treatment in Patients with Moderately to Severely Active Ulcerative Colitis: Interim Analysis from the Phase 3 U-Activate Open-Label Extension Study

Presenter: Panaccione R.

This interim analysis from the phase 3 U-ACTIVATE long-term extension study evaluated the long-term efficacy and safety of upadacitinib (UPA) in patients with moderately to severely active ulcerative colitis (UC) over approximately 5 years. Patients who responded to 8 weeks of UPA 45 mg induction therapy received maintenance treatment with placebo, UPA 15 mg, or UPA 30 mg daily before entering the long-term extension phase. At long-term extension week 192, more than 69% of patients receiving either UPA dose achieved clinical remission based on adapted Mayo score and partial Mayo score analyses. Among patients already in clinical remission at long-term extension baseline, more than 80% maintained remission through week 192 with both UPA doses.

More than 80% of patients achieved and maintained endoscopic improvement, while endoscopic remission was achieved in over 50% of patients at week 192. Among patients with endoscopic remission at baseline, remission was maintained through week 192 in 54% of patients receiving UPA 15 mg and 80% receiving UPA 30 mg. Treatment-emergent adverse event rates, serious adverse events, and discontinuations due to adverse events were similar between the two dose groups and remained consistent with previous safety analyses.

Overall, upadacitinib demonstrated sustained long-term clinical and endoscopic efficacy with a stable safety profile over 5 years in patients with UC.

Real-World Effectiveness of Upadacitinib in Patients with Moderate-to-Severe Ulcerative Colitis: Interim Findings on Treatment Patterns from the Profundus Study

Presenter: Parkes G.

This interim analysis from the prospective real-world PROFUNDUS study evaluated treatment patterns with upadacitinib (UPA) in patients with moderate-to-severe ulcerative colitis (UC) across 16 countries. The analysis included 494 patients with a mean age of 39.4 years; 54.6% were advanced therapy-experienced, and 14.2% had previously failed at least one Janus kinase inhibitor (JAKi). At baseline, 21.5% of patients were receiving corticosteroids (CS). At week 26, 82.8% of patients remained on UPA treatment, including 79.6% of advanced therapy-experienced patients and 86.6% of advanced therapy-naïve patients. The most common reasons for discontinuation were adverse events (6.3%), lack of efficacy (2.8%), and patient withdrawal (2.6%).

Most patients initiated and continued maintenance treatment with UPA 30 mg. By week 26, 80.6% remained on UPA30, while 14.1% were receiving UPA15. Advanced therapy-experienced patients were more likely to remain on UPA30 or escalate to UPA45 compared with advanced therapy-naïve patients. Among patients receiving corticosteroids at baseline, 52.2% remained on corticosteroids at the end of induction, decreasing to 33.9% by week 26.

Overall, the study demonstrated high treatment persistence with UPA in real-world practice and suggested a reduction in corticosteroid use over time.

Rifaximin Improves Global Symptoms in IBS-D: Meta-Analysis of Randomized Trials

Presenter: Ahmed Z.

This systematic review and meta-analysis evaluated the efficacy and safety of rifaximin in adults with diarrhoea-predominant irritable bowel syndrome (IBS-D) or irritable bowel syndrome without constipation. Six randomized double-blind trials involving approximately 1,400 participants were included. Most evidence came from three phase 3 trials and one retreatment trial. Rifaximin improved global IBS symptom response compared with placebo, with an absolute benefit of approximately 8–10% and a number-needed-to-treat of 10–12. Improvements were more consistent for bloating and abdominal distension than for abdominal pain alone. Stool consistency and stool frequency also showed modest benefit.

Safety outcomes were comparable between rifaximin and placebo. Rifaximin did not increase overall adverse events, serious adverse events, infection-related events, or Clostridioides difficile infection. Repeat treatment in the retreatment trial was also well tolerated with no new safety concerns.

Overall, short-course rifaximin provided modest but clinically meaningful symptom improvement in IBS-D with a favourable safety profile.

Efficacy and Safety up to 3 Years of Risankizumab Maintenance Treatment in Patients with Moderately to Severely Active Ulcerative Colitis: Interim Results from Phase 3 Command Open-Label Extension Study

Presenter: Atreya R.

This interim analysis from the ongoing COMMAND open-label extension (OLE) study evaluated the long-term efficacy and safety of Risankizumab (RZB) in patients with ulcerative colitis (UC) through OLE week 96, corresponding to approximately 3 years of maintenance treatment. The OLE included patients who completed the 52-week maintenance sub-study or responded to induction therapy. Most patients received subcutaneous RZB 180 mg, while patients who previously required rescue therapy received intravenous RZB 1200 mg followed by RZB 360 mg every 8 weeks.

At OLE week 0, approximately 90% of patients (N=1003) completed the study visit. Patients receiving RZB360 had more severe disease characteristics at baseline, including a higher proportion with inadequate response to advanced therapy (AT-IR) (76.8% vs 63.1%) and endoscopic score ≥3 (31.1% vs 12.1%) compared with the RZB180 group. Clinical remission per Adapted Mayo Score (AMS) at OLE week 0 was lower in the RZB360 group (25.2%) than in the RZB180 group (54.8%). A higher proportion of RZB360-treated patients also required OLE rescue therapy (34.5% vs 22.1%). Efficacy outcomes, including clinical remission, corticosteroid-free clinical remission, clinical response, endoscopic improvement, and endoscopic remission, remained stable from OLE week 0 through week 96. Sustained efficacy was observed in both AT-IR and non-AT-IR subgroups, although efficacy rates were numerically lower in AT-IR patients at week 96.

Safety findings were similar between the RZB180 and RZB360 groups for adverse events, severe adverse events, and serious adverse events. No new safety risks were identified during long-term treatment.

Overall, long-term RZB maintenance therapy demonstrated sustained clinical and endoscopic benefit through 3 years in patients with UC, with a consistent safety profile supporting long-term use.

DDW 2026, May 2-5, Chicago, IL