Comparative Effectiveness of Risankizumab and Upadacitinib in Crohn’s Disease Patients Previously Exposed to Biologics: Real-World Analysis

Presenter: Madabhushi S.

This retrospective cohort study compared real-world outcomes of Upadacitinib (Upa) and Risankizumab (Risa) in biologic-exposed adults with Crohn’s disease using the TriNetX Research Network. After 1:1 propensity score matching, 1,258 patients were included in each treatment group. Compared with Upa, patients receiving Risa had a significantly lower risk of requiring oral corticosteroids within 12 months (Risk ratio (RR) 0.85, 95% Confidence Interval (CI) 0.76–0.95) and a lower hazard of oral steroid use (Hazard ratio (HR) 0.85, 95% CI 0.74–0.98). Time to first oral steroid use also differed significantly between groups (P<0.05). Risa-treated patients had lower risks of inpatient admission (RR 0.70, 95% CI 0.60–0.83) and emergency department visits (RR 0.81, 95% CI 0.70–0.95), with significantly longer times to these events (P<0.05). No significant differences were observed in the need for intravenous steroids (RR 0.88, 95% CI 0.736–1.043; P=0.31) or bowel surgery (RR 0.69, 95% CI 0.47–1.01; P=0.08).

Patients receiving Risa were also 56% less likely to discontinue therapy compared with Upa (RR 0.44, 95% CI 0.37–0.52).

Overall, Risankizumab was associated with lower oral steroid use, reduced healthcare utilization, and lower treatment discontinuation compared with Upadacitinib.

Comparative Effectiveness of Upadacitinib versus Ustekinumab/ Risankizumab for Small Bowel Crohn’s Disease: A Multicenter Propensity Score Matched Study

Presenter: Tome J.

This retrospective cohort study compared real-world outcomes of Upadacitinib (UPA) versus Ustekinumab/Risankizumab (UST/RZA) in adults with isolated small bowel Crohn’s disease (CD) using the U.S. TriNetX database (January 2020–November 2024). After 1:1 propensity score matching, 1,583 patients were included in each cohort. Patients receiving UPA had a higher risk of requiring oral corticosteroids at both 6 months (adjusted hazard ratio [aHR] 1.19, 95% CI 1.03–1.39) and 12 months (aHR 1.22, 95% CI 1.07–1.39) compared with UST/RZA. The UPA cohort also had a higher risk of CD-related hospitalization at 6 months (aHR 1.21, 95% CI 1.02–1.42) and 12 months (aHR 1.21, 95% CI 1.06–1.39).

No statistically significant differences were observed between groups in the risk of switching to another advanced CD therapy or undergoing small bowel surgery at either 6 or 12 months.

Overall, UST/RZA therapy was associated with more favourable clinical outcomes than UPA in isolated small bowel CD.

Tulisokibart in Patients with Moderately to Severely Active Crohn’s Disease: Efficacy and Safety Through Week 146 from the Phase 2 Apollo-CD Study

Presenter: Siegel C.

This phase 2a open-label extension (OLE) study evaluated the long-term efficacy and safety of Tulisokibart, an anti-TL1A (Tumor necrosis factor-like ligand 1A) monoclonal antibody, in adults with moderately to severely active Crohn’s disease (CD) who responded to induction therapy in the APOLLO-CD study. A total of 37 induction responders were randomized to Tulisokibart 100 mg (n=19) or 250 mg (n=18) intravenously every 4 weeks. Median treatment duration in the OLE was 1.3 years for the 100-mg group and 2.6 years for the 250-mg group. Clinical remission based on Crohn’s Disease Activity Index (CDAI), patient-reported outcomes, endoscopic response, and endoscopic remission were maintained through week 146, with higher efficacy observed in the 250-mg group. Treatment-emergent adverse events (AEs) were reported in 94.4% of participants in the 250-mg group and 84.2% in the 100-mg group. Serious AEs occurred in 22.2% and 21.2% of participants, respectively, but none were considered related to Tulisokibart, and most were associated with underlying CD. No deaths were reported.

Six participants discontinued treatment because of AEs (4 in the 100-mg group and 2 in the 250-mg group). Exposure-adjusted incidence rates of AEs were generally lower with the 250-mg dose. No acute infusion reactions, serious hypersensitivity reactions, anaphylaxis, opportunistic infections, malignancies excluding nonmelanoma skin cancer, venous thrombosis, or suicidal ideation/behavior were reported. Infection rates were similar between groups (72.2% for 250 mg and 68.4% for 100 mg), with upper respiratory tract infection being the most common infection. Only one serious infection (infectious diarrhea) was reported.

Overall, Tulisokibart, particularly the 250-mg dose, demonstrated sustained efficacy and was generally well tolerated through 3 years of treatment, with no new safety signals identified.

Upadacitinib: Personalized Goals for Remission and Disease Evaluation in Patients with Crohn's Disease (Upgrade-CD) - A Multicentre Prospective Study from the Italian Group for the Study of Inflammatory Bowel Diseases (IG-IBD)

Presenter: Barberio B.

The UPGRADE-CD study is a prospective, multicentre, observational study evaluating the real-world effectiveness and safety of Upadacitinib (UPA) in adults with refractory Crohn’s disease (CD) treated at Italian referral centres. A total of 309 patients were included in this preliminary analysis. Clinical response rates remained high at both 3 months (58.3%) and 6 months (62.1%; p<0.001). Clinical remission rates were 54.7% at 3 months and 57.5% at 6 months (p<0.001). Steroid-free clinical response was achieved in 52.5% of patients at 3 months and 51.1% at 6 months. Steroid-free clinical remission rates were 47.9% and 46.6% at 3 and 6 months, respectively.

Endoscopic outcomes improved over time. Endoscopic improvement increased from 20.0% at 3 months to 43.5% at 6 months (p<0.001), while endoscopic remission was achieved in 40.1% of patients at 6 months (p<0.01). Mean faecal calprotectin levels decreased from 986.7 ± 1619.9 at baseline to 362.0 ± 743.3 at 6 months (p<0.001). Mean C-reactive protein (CRP) levels also declined significantly, from 62.3 ± 197.4 mg/L at baseline to 17.1 ± 37.2 mg/L at 6 months (p<0.001). UPA discontinuation occurred in 18 patients by month 3 and 21 patients by month 6 due to lack of efficacy or adverse events. Adverse events accounted for 6 of 18 discontinuations at 3 months and 7 of 21 discontinuations at 6 months.

Overall, this preliminary real-world analysis showed that UPA achieved high clinical and steroid-free remission rates, improved endoscopic outcomes, and had a favourable safety profile over 6 months in patients with refractory CD.

Durable Efficacy of Risankizumab Through Week 148 in Patients with Moderate-to-Severe Crohn’s Disease: A Post Hoc Analysis of Part 2 of the Sequence Study

Presenter: Atreya R.

This post hoc analysis from the ongoing SEQUENCE study evaluated the long-term durability of Risankizumab (RZB) efficacy over 148 weeks in patients with moderate-to-severe Crohn’s disease (CD) and prior anti-tumor necrosis factor (anti-TNF) treatment failure. A total of 224 patients who completed the initial 48-week head-to-head phase versus ustekinumab entered Part 2 and received open-label maintenance RZB 360 mg subcutaneously every 8 weeks. Among patients who achieved clinical remission at week 8, most maintained remission through later timepoints. At week 148, clinical remission was maintained in 98.5% of patients based on the Crohn’s Disease Activity Index (CDAI) and in 88.1% based on stool frequency/abdominal pain score (SF/APS). Durable clinical remission was also observed in patients who achieved remission at week 48.

Among patients who achieved endoscopic response, endoscopic remission, or mucosal healing at week 24, corresponding outcomes were maintained at week 148 in 84.7%, 78.2%, and 67.3% of patients, respectively. Similar durability was observed among patients who achieved these endpoints at week 48. Analyses using modified nonresponder imputation showed results similar to the as-observed analysis.

Overall, patients with moderate-to-severe CD and prior anti-TNF failure demonstrated sustained clinical and endoscopic benefits with RZB treatment through nearly 3 years.

Long-Term Efficacy of Upadacitinib in Patients with Moderate-to-Severe Crohn’s Disease and Prior Biologic Use

Presenter: Atreya R.

This post hoc analysis from the ongoing U-ENDURE long-term extension (LTE) study evaluated the long-term efficacy of upadacitinib (UPA) in patients with moderate-to-severe Crohn’s disease (CD) through 96 weeks of LTE treatment, corresponding to 3 years of total maintenance therapy. Outcomes were assessed according to prior inadequate response or intolerance to biologic therapy (Bio-IR). Patients who completed 52 weeks of maintenance treatment in U-ENDURE continued their assigned treatment with UPA 15 mg (UPA15) or UPA 30 mg (UPA30) once daily during the LTE. The Bio-IR subgroup included 70 patients receiving UPA15 and 119 receiving UPA30, while the non-Bio-IR subgroup included 37 patients on UPA15 and 54 on UPA30. From LTE week 0 to week 96, at least 63.0% of patients achieved and maintained clinical remission based on stool frequency/abdominal pain score (SF/APS), and at least 59.1% achieved and maintained endoscopic response across both Bio-IR and non-Bio-IR subgroups, regardless of UPA dose.

Clinical remission based on Crohn’s Disease Activity Index (CDAI) was achieved and sustained in at least 71.0% of patients throughout the LTE in both subgroups and treatment groups. Rates of endoscopic remission, ulcer-free endoscopy, and deep remission were either maintained or numerically higher at week 96 compared with week 0, irrespective of Bio-IR status or treatment dose.

Overall, sustained clinical and endoscopic efficacy was observed with upadacitinib through 3 years of maintenance treatment in patients with CD, regardless of prior inadequate response or intolerance to biologic therapy.

One-Year Efficacy of Upadacitinib in Perianal Crohn’s Disease: A Multicenter Cohort Study

Presenter: Richard N.

This retrospective multicentre cohort study evaluated the real-world effectiveness and safety of upadacitinib in patients with active refractory perianal Crohn’s disease (CD) treated across 13 French centres between September 2022 and August 2025. A total of 59 patients were included, of whom 43 (73%) had fistulizing perianal CD and 16 (27%) had isolated primary anal ulcerations. The median age was 38 years (interquartile range: 29–47 years), 49% were male, and 19% were active smokers. All patients had prior exposure to at least two biologic therapies, with a median of four prior biologics (range: 3–5). Previous perianal surgery had been performed in 68% of patients overall and in 79% of patients with fistulizing disease. Among patients with fistulizing perianal CD, clinical remission rates with upadacitinib were 12% at 3 months, 26% at 6 months, and 26% at 12 months. Clinical response rates were 63%, 49%, and 30% at 3, 6, and 12 months, respectively.

Magnetic resonance imaging (MRI)-based outcomes at 12 months showed an MRI response in 64% (9/14) of evaluated patients and MRI remission in 7% (1/14) of patients with fistulizing perianal CD. In patients with isolated anal ulcerations, complete ulcer healing was observed in 25% (4/16) at 12 months. Univariate analysis did not identify any clinical or demographic factors associated with clinical remission at 12 months. A total of 16 adverse events were reported in 14 patients (27%). Serious adverse events occurred in 3 patients (5%) and were related to CD exacerbations. At 12 months, 17% of patients required perianal drainage surgery, while 27% discontinued upadacitinib because of lack of efficacy.

Overall, this real-world study showed that upadacitinib achieved clinical remission in approximately one-quarter of patients with refractory perianal CD after 1 year of treatment.

Real-World Effectiveness and Safety of Upadacitinib in Difficult-to-Treat Crohn’s Disease: A National Multicenter Study from China

Presenter: Zhang Z.

This ambi-directional, national, multicentre study evaluated the real-world efficacy and safety of upadacitinib (UPA) in patients with difficult-to-treat Crohn’s disease (DTT-CD) across eight inflammatory bowel disease (IBD) centres in China between January 2023 and January 2025. Patients meeting the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) criteria for DTT-CD received UPA 45 mg once daily during a 12-week induction phase, followed by 15 mg once daily for maintenance. Efficacy and safety were assessed at weeks 12 and 24. A total of 151 patients were enrolled in the study, and endoscopic evaluation at week 24 was completed in 89 patients. At week 24, the clinical remission rate was 63.2%, while endoscopic remission was achieved in 28.9% of patients. Clinical response was observed in 82.9% of patients, and endoscopic response was reported in 42.2% at week 24.

Safety analysis showed that 42 adverse events (AEs) were reported by week 12, with no serious adverse events (SAEs) observed during this period. By week 24, 32 AEs had been reported. These included acne (n=10), anemia (n=7), fever (n=3), blue semen in male patients (n=2), fatigue (n=1), herpes zoster (n=1), vaginitis (n=1), hematuria (n=1), rash (n=1), leukopenia (n=1), and mild elevation of creatine kinase (n=1). Serious adverse events reported at week 24 included lower limb venous thrombosis (n=1), intestinal perforation (n=1), and massive hemorrhage (n=1). The study noted blue semen as a newly observed adverse event in this setting.

A total of 9 patients discontinued UPA treatment by week 24. Among these, 3 patients discontinued because of serious adverse events requiring hospitalization. Other reasons for discontinuation included fever (n=2), anemia (n=1), and lack of endoscopic response (n=3).

Overall, this study, described as the largest cohort of Asian patients with DTT-CD to date, demonstrated that UPA provided sustained clinical and endoscopic efficacy in a real-world Chinese population with a manageable safety profile.

Insights from Real-World Dosing Patterns and Outcomes of High Dose Upadacitinib in Severely Refractory Crohn’s Disease

Presenter: Proksell S.

This retrospective cohort study evaluated the long-term effectiveness of extended high-dose upadacitinib (45 mg) in patients with difficult-to-treat Crohn’s disease (CD) who required prolonged high-dose therapy or dose re-escalation after relapse on maintenance treatment. The study included 51 patients, with a mean age of 40.2 years; 52.9% were male. The average duration of high-dose upadacitinib treatment was 67.6 weeks. Baseline mean C-reactive protein (CRP) and fecal calprotectin (FCal) levels were 12.37 and 1367.00, respectively. Both inflammatory markers showed sustained reductions over time. At more than 12 months of therapy, mean CRP decreased to 5.45 and mean FCal decreased to 320.28.

From baseline to beyond 12 months, both CRP and FCal reductions were statistically significant (CRP reduction: -8.96, p=0.0036; FCal reduction: -1074.32, p=0.0040). Between 6–12 months and >12 months, FCal continued to significantly decrease (p=0.049), while CRP showed a non-significant decline.

Overall, extended high-dose upadacitinib was associated with sustained biochemical remission beyond 12 months in patients with severe, refractory CD.

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