Upadacitinib Treatment Outcomes in Crohn’s Disease: A Retrospective Analysis of Clinical Response and Perianal Fistula Resolution

Background Intestinal and perianal fistulas and fissures are associated with significant morbidity and decreased quality of life in patients with Crohn’s disease (CD). We evaluated rates of fistula and fissure improvements with upadacitinib (UPA), an oral selective Janus kinase inhibitor, in patients with CD who had fistulas or fissures at baseline in phase 3 induction and maintenance trials. Methods In the U-EXCEL (NCT03345849) and U-EXCEED (NCT03345836) phase 3 induction trials, patients with moderate-to-severe CD were randomized to UPA 45 mg once daily (QD) or placebo (PBO) for 12 weeks. Patients who achieved clinical response after 12 weeks of induction were eligible for U-ENDURE (NCT03345823) and rerandomized to UPA 30 mg QD, UPA 15 mg QD, or PBO for an additional 52 weeks of maintenance treatment. Fistula activity was assessed by presence of external openings and draining upon gentle compression. Presence of perianal fissures was also assessed. The proportion of patients with external closure of fistula openings, complete resolution of draining, and ≥ 50% reduction in draining was recorded at weeks 12 and 52. Endpoints were analyzed using non-responder imputation. Results Of 1021 enrolled patients, 143 patients had fistulas (124 [86.7%] perianal; 19 [13.3%] enterocutaneous) and 54 patients had perianal fissures at baseline. The proportion of patients who achieved external closure of fistula openings was higher with UPA vs PBO at week 12 (Fig 1A) and at week 52 (Fig 2A). The proportion of patients who achieved complete resolution of draining and ≥ 50% reduction in draining was higher with UPA vs PBO at week 12 (Fig 1B and 1C) and at week 52 (Fig 2B and 2C). A higher proportion of patients achieved complete resolution of fissures with UPA vs PBO at week 12 (Fig 1D) and at week 52 (Fig 2D). At weeks 12 and 52, a higher proportion of patients with fistulas treated with UPA vs PBO achieved clinical remission and endoscopic response (Fig 1E and 2E). Rates of adverse events (AEs), serious AEs, or AEs leading to study drug discontinuation were similar in UPA groups compared with PBO during the induction and maintenance periods. Rates of abscess formation were 1.8% with UPA 45 mg and 6.8% with PBO at week 12, and 3.0% with UPA 30 mg, 6.4% with UPA 15 mg, and 2.5% with PBO at week 52. Conclusion Among patients with CD complicated with fistulas and/or fissures at baseline, UPA treatment led to higher rates of external closure of fistula openings, resolution of draining, and healing of fissures, along with clinical remission and improvements in luminal disease compared with PBO. No new safety concerns were identified.

Upadacitinib (UPA) has demonstrated efficacy in clinical trials and was approved in 2023 for treating adults with moderately to severely active Crohn’s disease (CD) in the United States (US). Understanding real-world patient characteristics and treatment patterns is important to support clinical decision-making. This study evaluated the characteristics and early treatment patterns in patients with CD initiating treatment with UPA using real-world evidence. This retrospective cohort study was conducted from May 2023 to December 2024 using US healthcare claims data from the Merative™ MarketScan Research database. Patients ≥18 years initiating UPA 45 mg once daily induction treatment were included if they had ≥1 inpatient or 2 outpatient claims with a CD diagnosis (≥1 claim in the baseline period) and were continuously enrolled for ≥6 months before and ≥6 months after the index date. Patient demographics and baseline characteristics were summarized using descriptive analyses. Treatment patterns such as adherence (proportion of days covered [PDC], defined by percentage of available UPA days’ supply in the follow-up period), persistence (time on UPA [days] until a gap of 60 days was observed in the follow-up period), dose escalation and de-escalation were evaluated. Outcomes were described at 6 months and were stratified by prior line of advanced therapy (LOT). A total of 704 patients were identified with ≥6 months of follow-up data. Mean age was 41 years, 48% were female, 70% were tumor-necrosis factor inhibitor (TNFi)-experienced, 23% were non-TNFi biologic-experienced, 61% had prior exposure to 1 or 2 LOT and 32% had prior exposure to 3+ LOT. Overall, 87% (n = 611) of patients moved from UPA 45 mg induction to maintenance. Of these patients, 21% received UPA 15 mg and 79% received UPA 30 mg (Figure). At 6 months, mean (standard deviation [SD]) PDC was 0.81 (0.25) and 82% of patients demonstrated treatment persistence with UPA (Table). In TNFi-experienced versus non-TNFi-biologic experienced patients, mean PDC and the proportion of patients persisting on treatment were similar. Overall, 19% of patients escalated their dose from 15 to 30 mg and 2% de-escalated from 30 to 15 mg (Table). Patients who used UPA in earlier LOT (1 or 2) compared with later LOT (3+) had higher adherence (0.83 [0.23] or 0.84 [0.23] vs 0.78 [0.27]), higher persistence (85% or 86% vs 77%), and lower dose escalation (17% or 22% vs 25%). This real-world US claims analysis showed approximately 85% of patients remained on UPA from induction to maintenance. Overall, the outcome journeys of patients were better when UPA was used in earlier lines of therapy. Findings were consistent with the observations in the UPA clinical trials in patients with CD. Future analyses will evaluate outcomes with a longer follow-up period. Figure 1:Table 1:

Background Corticosteroids (CS) may be used for induction of remission in Crohn’s disease (CD); however, side effects, toxicities, and low rates of mucosal healing may limit their long-term use. Safety and efficacy of upadacitinib (UPA), an oral selective Janus kinase inhibitor, were evaluated among patients with CD receiving UPA with CS at baseline in phase 3 clinical trials. Methods In 2 phase 3 studies (U-EXCEL, NCT03345849; U-EXCEED, NCT03345836), patients with moderate-to-severe CD were randomized to 12-week induction with UPA 45 mg once daily (QD) or placebo (PBO). Patients who achieved clinical response to UPA 45 mg were rerandomized in U-ENDURE (NCT03345823) to UPA 30 mg QD, UPA 15 mg QD, or PBO for a 52-week maintenance period. Patients taking CS at baseline or week 0 of maintenance (end of induction) were included. A CS taper began at induction week 4 and continued during maintenance. Endpoints included the proportion of patients who discontinued CS use (CS-free) at week 12 or for ≥ 90 days prior to week 52, and achieved clinical remission by stool frequency/abdominal pain score or by Crohn’s Disease Activity Index (CDAI), enhanced clinical response, decrease of at least 100 points in CDAI from baseline, endoscopic remission, and endoscopic response at week 12 and week 52. CS daily dose (in prednisone equivalent doses) was recorded. Safety was assessed through induction and maintenance. Results Of 1021 patients evaluated, 358 (35.1%) were taking CS at baseline (mean daily prednisone equivalent dose, 23.0 mg). Greater changes from baseline in mean CS daily dose were observed with UPA vs PBO at induction week 12 (−17.3 mg vs −10.7 mg); these changes were sustained at maintenance week 52 (UPA 30 mg, −16.4 mg; UPA 15 mg, −17.4 mg; PBO, −14.7 mg). The proportion of patients who achieved a ≥ 50% reduction in CS daily dose was higher with UPA vs PBO at induction week 12 among patients taking CS at baseline (72.6% vs 48.4%) and at week 52 among patients taking CS at baseline or week 0 of maintenance (UPA 30 mg, 49.2%; UPA 15 mg, 44.4%; PBO, 11.1%). A significantly higher proportion of patients taking UPA vs PBO were CS-free and achieved clinical remission, clinical response, endoscopic response, and endoscopic remission at week 12 (Fig 1A) and week 52 (Fig 1B). Rates of adverse events (AEs), serious AEs, and discontinuation were comparable between groups (Table 1). Serious infections, opportunistic infections, and herpes zoster events were numerically higher with UPA vs PBO (Table 1). Conclusion Patients with CD taking CS were able to taper and discontinue their CS regimen and experience clinical and endoscopic improvements with UPA treatment during the induction and maintenance periods.

Background Upadacitinib (UPA) and risankizumab (RSK) are alternatives for Crohn’s disease (CD) patients refractory to conventional therapies or biologics, although their optimal positioning is unclear. Aims to compare the durability and effectiveness of UPA and RSK after biologic failure in CD; to identify risk factors for relapse and for therapy discontinuation; and to explore safety profile of UPA and RSK in this scenario. Methods Adult patients from the prospectively-maintained ENEIDA registry of GETECCU who received UPA or RSK as second- (after 1 anti-TNF) or third-line (after 2 anti-TNFs, after 1 anti-TNF+vedolizumab, or after 1 anti-TNF+ustekinumab) with ≥12 weeks of follow-up, were included. Clinical remission was defined as Harvey-Bradshaw Index (HBI) ≤ 4, and clinical response as a decrease in HBI > 3 points. Biologic remission was considered as faecal calprotectin (FC) ≤ 250 µg/g, and biologic response as a reduction of ≥ 50% in FC levels. Endoscopic activity was graded as quiescent (remission), mild, moderate or severe (as endoscopist’s criteria); and radiologic activity as absence/presence according to radiologist. Outcomes were evaluated at 12, 24, and 48 weeks. Treatment durability was analysed using Kaplan-Meier curves, and factors for therapy discontinuation and relapse were identified by Cox regression. All adverse events (AEs) were recorded. Results A total of 562 patients from 39 centers were included [UPA: n = 242 (43%), RSK: n = 320 (57%)] (Table 1). In second-line, 12 and 24-week durability was 70%/59% for UPA and 72%/72% for RSK; in third-line, 61%/40% for UPA, and 80%/76% for RSK (p < 0.05). Outcomes were included in Table 2. In second-line, predictive factors for therapy discontinuation were stricturing-fistulising behaviour (Hazard Ratio [HR]=1.9, 95% confidence interval [CI]=1.1-3.3), and UPA vs. RSK treatment (HR = 1.8, 95%CI=1.1-3.1). In third-line, UPA treatment was associated with treatment discontinuation (HR = 2.4, 95%CI=1.5-4). The severity of CD at baseline was associated with relapse in second- (HR = 7.1, 95%CI=3.9-12.7) and in third-line (HR = 5.4, 95%CI=3.4-8.7). AEs were reported in 64 (28%) UPA- and 28 (10%) RSK- treated patients (p < 0.05), most commonly acne for UPA, while infections predominated with RSK. Treatment was maintained in 81% of UPA and 91% of RSK patients with AEs (p < 0.05). Conclusion UPA and RSK are effective options after biologic failure in CD patients. Both agents showed high treatment durability with greater persistence observed for RSK in third-line. CD behaviour and UPA treatment (vs. RSK) were predictive factors for therapy discontinuation, while severity of CD at baseline predicted relapse. AEs occurred more frequently with UPA, leading to a higher rate of treatment discontinuation compared with RSK.

Background Upadacitinib (UPA), a selective JAK1 inhibitor, has shown robust efficacy in clinical trials for Crohn’s disease (CD) and ulcerative colitis (UC). However, real-world evidence in Asian populations remains limited. We aimed to evaluate the real-world effectiveness and safety of UPA in Korean patients with CD and UC across multiple centers. Methods We conducted a retrospective study across three Korean academic centers including adults with UC or CD treated with UPA. A total of 79 patients were analyzed (UC 30; CD 49). Clinical, biochemical, and endoscopic outcomes were assessed at week 16 for UC and week 12 for CD, and adverse events (AEs) were evaluated throughout follow-up. Results Among 79 patients, 88.6% (70/79) had prior exposure to at least one biologic therapy. In UC (n = 30), baseline disease activity was moderate to severe (median partial Mayo 8; endoscopic subscore 3). By week 16, substantial improvements were observed, with reductions in the partial Mayo score (to 2), endoscopic subscore (to 0), CRP, and fecal calprotectin (4034.8 → 185.5 μg/g). The UPA continuation rate was 96.7%, with discontinuation due to loss of response (n = 1) or an adverse event (n = 1). (Table 1) In CD (n = 49), baseline CDAI was high (mean 284.8), with a mean SES-CD of 10.4 and a median of two prior advanced therapies. By week 12, CDAI improved to 80.3, accompanied by reductions in CRP and fecal calprotectin (1408.6 → 458.4 μg/g). The UPA continuation rate was 83.6%, with discontinuation due to primary non-response (n = 1), loss of response (n = 5), or adverse events (n = 2). (Table 2) Across the entire cohort, the most frequent AEs were acne (49.4%), lymphopenia (11.4%), anemia (6.3%), herpes zoster (5.1%), and infections (6.3%); no thromboembolic events or malignancies occurred. (Table 3). Conclusion Upadacitinib demonstrated substantial clinical, biochemical, and endoscopic improvements in both UC and CD in this real-world Korean multicenter cohort. High continuation rates, particularly in UC, support its effectiveness even in biologic-experienced patients. The safety profile was consistent with clinical trials, with no thromboembolic events or malignancies observed. These findings support UPA as an effective and well-tolerated therapeutic option for refractory IBD in routine practice.support UPA as an effective and well-tolerated therapeutic option for refractory IBD in routine practice. Conflict of interest: Prof. Dr. Lee, Jun: No conflict of interest Kim, Seong Jung: No conflict of interest Choi, Geunhyuk: No conflict of interest Jung, Yunho: No conflict of interest Baek, Donghoon: No conflict of interest

Cumulative Evidence That Mesenchymal Stem Cells Promote Healing of Perianal Fistulas of Patients With Crohn's Disease–Going From Bench to Bedside

Background Perianal fistulas are common and cause significant quality of life impairment in patients (pts) with Crohn’s disease (CD). In previous phase 2/3 studies, ustekinumab (UST) showed some evidence of efficacy on fistula resolution, with no clear dose-response relationship. Additional studies are needed to evaluate the role of UST in perianal fistula treatment. Here, we report fistula data from two recent studies of UST in CD, SEAVUE and STARDUST. Methods In SEAVUE, biologic-naïve pts with moderate-to-severe CD were randomized to receive blinded UST (⁓6mg/kg IV at baseline then 90mg SC q8w) or adalimumab (ADA; 160/80mg SC at baseline/W2, then 40mg SC q2w). In STARDUST, biologic-naïve and biologic-failure pts with moderate-to-severe CD received open-label UST ⁓6mg/kg IV at baseline and UST 90mg SC at W8. At W16, pts were randomized to maintenance treatment under standard of care (90mg SC q12w or q8w) or treat-to-target (90mg SC q12w or q8w with potential adjustment to q4w) regimens. In both trials, the number of open and draining perianal fistulas was evaluated at baseline and the end of maintenance (SEAVUE W52, STARDUST W48). Fistula resolution was defined as closure of all fistulas. Pts with missing data at W52/W48 were considered to not have been in fistula resolution. In SEAVUE, pts who had a prohibited CD-related surgery, discontinued for lack of efficacy or an adverse event of worsening CD, or had prohibited concomitant medication changes before W52 were considered not to be in fistula resolution. Results In SEAVUE, 7 of 13 pts (53.8%) with active perianal fistulas at baseline in the UST group had complete fistula resolution at W52, and 6 of 16 patients (37.5%) in the ADA group had fistula resolution. In STARDUST, 9 of 19 pts (47.4%) with active perianal fistulas at baseline had complete fistula resolution at W48. Of the 9 pts in fistula resolution, 2 were receiving q12w at W48, 6 were receiving q8w, and 1 was receiving q4w. Of the 10 pts without fistula resolution, 2 were receiving q12w at W48, 3 were receiving q8w, 1 was receiving q4w and 4 discontinued before W48. In both studies, among pts with evaluable samples for pharmacokinetic analysis, fistula closure at W52/48 was not associated with higher serum drug concentrations at either the early time point of W16 or at the end of maintenance (Figure). This result was consistent for UST in both studies as well as ADA in SEAVUE. Conclusion Of pts with perianal fistulas at baseline in SEAVUE and STARDUST who received UST (32 pts in total), half were in fistula resolution after ~1 year of maintenance treatment. No relationship was observed between fistula resolution and serum drug concentrations, but no definite conclusions can be drawn given the relatively small sample size.

AB0255 BASELINE CHARACTERISTICS OF PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH UPADACITINIB IN GERMAN REAL-WORLD PRACTICE: RESULTS FROM THE POST-MARKETING OBSERVATIONAL UPwArds STUDY

Background Upadacitinib (UPA) is the first oral JAK inhibitor approved for the treatment of Crohn's disease (CD). While its effectiveness and safety are well-documented in pivotal clinical trials, real-world data remain limited. Aim: To evaluate the real-world efficacy and safety of UPA in both the short and long term for CD patients. Methods A multicentre, prospective, observational study was conducted on patients receiving UPA since its approval. Epidemiological, clinical and disease-related variables, cardiovascular risk factors (CVRF) and prior treatments, were collected. Disease activity was assessed using the Harvey-Bradshaw Index (HBI), endoscopic/radiological (E/R) evaluations, C-reactive protein (CRP), and faecal calprotectin (FC) levels at baseline, 12, 24, and 52 weeks (W). Adverse events (AEs) hospitalisations, and treatment discontinuations were also recorded. Results A total of 300 CD patients were included (mean follow-up of 42 W (SD 27.4)). Of these, 26 (9%) received UPA in combination with biological therapy, 24 (8%) were treated for extraintestinal manifestations (EIM) without luminal disease, and 250 (83%) for luminal CD. Baseline characteristics are presented in Figure 1. Regarding prior advanced therapies, 15% had received one, 26% two, 29% three and 29% ≥four. At baseline, 70% of patients (210) underwent E/R evaluations, which revealed moderate or severe disease activity in 45% and 37%, respectively. Clinical remission was achieved in 62%, 65% and 67% of patients at W12, 24, 52. FC and CRP levels returned to normal (<250 μg/g and <3 mg/L respectively) in the 50%, 55% and 62%, and 60%, 64% and 65% of the patients at W12, 24 and 52, respectively. Over the follow-up period, HBI, FC, and CRP levels significantly improved (Figure 2) and 113 patients (40%) underwent E/R evaluations of which 16% and 32% showed inactive or mild disease activity, respectively. Patients receiving combination therapy showed significant improvement in HBI though decreases in CRP and FC were not statistically significant. Among those treated for EIM, HBI and FC levels remained normal, while CRP showed a significant reduction. AEs occurred in 68 patients (23%), including 29 discontinuations (43%) without associated mortality. Hospitalisation occurred in 58 patients (19%), and surgery in 26 (9%). Treatment discontinuation occurred in 90 patients (30%) within 52 W due to primary non-response in 51%, loss of response in 13%, AEs in 32%, and other reasons in 4%. Conclusion This study highlights the real-world efficacy and safety profile of UPA in CD, particularly in patients with aggressive disease or EIM. Further research is warranted to optimise treatment strategies and outcomes in more heavily pre-treated populations.

Limited data are available regarding the relationship between anti-tumor necrosis factor (TNF) drug/antibody levels and perianal fistula outcomes in Crohn's disease. The aims of this study were to assess the relationship between maintenance anti-TNF levels and perianal fistula outcomes. This was a retrospective cross-sectional study of patients receiving maintenance adalimumab or infliximab therapy (minimum 24 weeks) for the treatment of Crohn's disease with associated perianal fistulas, who had anti-TNF drug/antibody levels (trough for infliximab) measured within 4 weeks of clinical assessment. The primary outcome was the association of anti-TNF levels with perianal fistula healing defined as the absence of drainage. The secondary outcome was the association of anti-TNF levels with complete perianal fistula closure. A total of 64 patients (adalimumab, n = 35; infliximab, n = 29) were included. Patients with fistula healing had higher levels of anti-TNF vs. those without fistula healing (adalimumab: 12.6 vs. 2.7 μg/mL, P < 0.01; infliximab: 8.1 vs. 3.2 μg/mL, P < 0.01). Patients with fistula closure also had significantly higher anti-TNF levels vs. those without fistula closure (adalimumab: 14.8 vs. 5.7 μg/mL, P < 0.01; infliximab: 8.2 vs. 3.2 μg/mL, P < 0.01). For adalimumab, receiver operator characteristic analysis identified an optimum level of >6.8 μg/mL and >9.8 μg/mL for fistula healing and closure, respectively. For infliximab, receiver operator characteristic analysis identified an optimum trough level of >7.1 μg/mL for both fistula healing and closure. Higher maintenance anti-TNF levels are associated with perianal fistula healing and closure in Crohn's disease.

Background Upadacitinib (UPA), an oral Janus kinase inhibitor (JAKi), is approved for the treatment of moderate-to-severe ulcerative colitis (UC).1,2 The Prospective Real-World Study of UPA in UC (PROFUNDUS) is an open-label, noninterventional study evaluating physician prescribing patterns and clinical endpoints among UPA-treated patients with moderate-to-severe UC in routine clinical practice (initiated 15Aug2022); this interim analysis assesses real-world (RW) clinical effectiveness, symptomatic improvement, and safety.4 Methods Patients, comprising 494 of the first 500 eligible adults (18-79 years [yrs]), in the full analysis set (FAS), with moderate-to-severe UC who initiated once-daily UPA across 16 countries, per investigator discretion and according to the local label; steroid tapering was not mandated and left to investigator discretion. Baseline (BL) demographics and disease characteristics were reported among FAS; endpoints assessed included clinical response per Partial Adapted Mayo score (PAMS), corticosteroid (CS)-free response per PAMS, clinical remission (CR) per Partial Mayo score, absence of abdominal pain, and absence of bowel urgency at week 26 among evaluable FAS pts and by advanced therapy (AT) status (AT-experienced vs AT-naive; cut-off date: 28Feb2025). Safety endpoints were assessed, with treatment-emergent adverse events (TEAEs) reported as counts and percentages. Results Among FAS at BL (last measurement on or before the initial UPA dose), the mean (SD) patient age was 39.4 (13.3) yrs, with 57.1% males, 21.5% on CS; mean (SD) disease duration was 7.8 (7.0) yrs, with 54.6% of patients being AT-experienced, 41.9% failed ≥1 TNF, and 14.2% failed ≥1 JAKi. At week 26, 81.8%, 72.4%, 66.3%, and 71.9% of patients achieved clinical response, CR, no abdominal pain, and no bowel urgency, respectively; among those on BL CS, 64.4% attained CS-free response (Table 1). Similar results were observed for all endpoints regardless of AT status (Table 1). Among patients treated with UPA45/UPA15, UPA45/UPA30, or any UPA dose, TEAEs were as follows: any AE, 66.0%; 50.8%; 51.4%, serious AEs, 3.8%; 4.6%; 5.7%, and severe AEs, 5.7%; 4.0%; 5.5% (Table 2). Within this overall cohort, the subgroup of patients who experienced TEAEs potentially related to UPA exhibited serious and severe AEs at 3.6%, 6.3%, 6.9%, and 7.1%, 5.4%, 6.9%, respectively (Table 2). Conclusion In the PROFUNDUS study, UPA-treated patients with UC achieved high rates of clinical and symptomatic improvement, regardless of AT status within an RW setting. Overall, UPA was well-tolerated, with few serious AEs observed, most of which were unrelated to UPA, as determined by the study investigator.

Background Upadacitinib (UPA) has demonstrated efficacy and safety for Crohn’s disease (CD) and ulcerative colitis (UC) in pivotal trials.1,2 However, real-world data in Asian patients remain limited. Methods We conducted a retrospective multicentre study including patients with CD or UC who initiated UPA across six referral hospitals in Korea between September 2023 and January 2025. Clinical remission/response, endoscopic outcomes (UC), biochemical outcomes, and safety were evaluated (week 12/24/52 in CD; week 16/52 in UC). Clinical remission was defined as CDAI &amp;lt;150 together with clinical response (CD) and partial Mayo score ≤2 with combined rectal bleeding [RB] and stool frequency scores ≤1 (UC). Clinical response was defined as CDAI reduction ≥100 (CD) and reduction in partial Mayo score ≥3 with ≥30% decrease and RB score decrease ≥1 or absolute RB score ≤1 (UC). Endoscopic remission was defined as MES = 0 or UCEIS = 0; endoscopic response as ≥ 1-point MES reduction or ≥ 2-point UCEIS reduction. Biochemical remission (CRP remission and Faecal calprotectin[FC] remission) were defined as CRP &amp;lt;0.6 mg/dL (for those with baseline ≥0.6) and FC &amp;lt; 250 µg/g (for those with baseline ≥250), respectively. Results A total of 187 patients (119 CD, 68 UC) were included. Among patients with CD, the median disease duration was 127 months and 87.4% had prior biologic exposure. Clinical remission was achieved in 50.0% (43/86), 49.4% (42/85), and 29.0% (9/31) at weeks 12, 24, and 52, while clinical response was achieved in 53.5% (46/86), 55.3% (47/85), and 32.3% (10/31), respectively (Figure 1). CRP remission was observed in 63.3% (38/60), 55.0% (33/60), and 37.0% (10/27), and FC remission in 26.2% (28/107), 26.2% (27/103), and 8.8% (3/34) at the corresponding time points. Among patients with UC, 76.5% had prior biologic exposure. Clinical remission was achieved in 83.1% (54/65) and 59.3% (16/27) at weeks 16 and 52, while clinical response was achieved in 83.1% (54/65) and 63.0% (17/27), respectively (Figure 1). Endoscopic remission was observed in 33.8% (23/68) and 31.0% (9/29), and endoscopic response in 69.1% (47/68) and 48.3% (14/29) at weeks 16 and 52. CRP remission achieved in 75.0% (33/44) and 50.0% (9/18), and FC remission in 28.8% (19/66) and 37.0% (10/27) at each time point. In UC, higher baseline serum albumin was associated with week 16 endoscopic remission (OR 4.95; 95% CI 1.59–20.8), and prior biologic exposure was negatively associated (OR 0.23; 95% CI 0.05–0.83). Acne was the most common adverse event (27.3%, 55.25/100 person-years), whereas serious adverse events were rare (Table 1). Conclusion UPA demonstrated favourable effectiveness and safety in Korean patients with IBD, with outcomes comparable to Western real-world data.

Background Upadacitinib (UPA), a janus kinase inhibitor (JAKi) with selectivity for JAK-1, is licensed in ulcerative colitis (UC) and Crohn’s disease (CD). Acne was seen commonly in the CD and UC registration studies of UPA. We sought to investigate the prevalence of acne in a real-world cohort of IBD patients using UPA. Methods We performed a retrospective review of all patients who received UPA for UC, CD or IBD-unclassified (IBD-U) between Sep 2022 and Sep 2024 at a large tertiary referral centre. Data were collated from electronic health records supplemented by telephone calls to individual patients. Demographic data, previous advanced treatments, dose and length of time on UPA were recorded in addition to skin related adverse effects. Self-reported acne was considered acceptable as a diagnosis, given that it is easily recognisable by the general public. Results The patient cohort is described in table 1. Out of 159 eligible subjects, 132 (83%) were reachable by telephone, 50 (38%) of whom were females. The indication for UPA was UC (67, 51%), CD (60, 45%), and IBD-U (5, 4%). 14 patients (11%) reported a history of acne at time of starting UPA and 60 (45%) were aware that acne was a potential side effect prior to starting the medication (Table 1). After a median duration of UPA therapy of 10 months (IQR 4-12), acne was reported by 77 (58%) patients (34 (51%) UC and 39 (65%) CD; 50 (61%) male and 27 (54%) female). Acne was reported to have involved the face (n=30, 41%), body (n=7, 9%) or both (n=37, 50%). The majority of UPA-associated acne was reported during the initial higher dose 45mg daily induction period (70, 91%) although acne persisted in 45 (58%) patients after reduction to 30mg. Notably, 35 (45%) patients with UPA-associated acne consulted their general practitioners, and 15 (19%) required specialist input from dermatologists. Importantly, acne-induced UPA dose reduction occurred in 4 (5%) patients and 3 (4%) patients discontinued UPA because of acne (Table 1). Conclusion The study suggests that self-reported acne is very common amongst patients who are receiving UPA for IBD, although acne-driven dose reduction or discontinuation is infrequent. Nearly half of the affected patients required GP assessments, and one fifth needed specialist dermatology input, suggesting substantial patient inconvenience and considerable impact on healthcare resource utilisation. Specific risk factors for acne, as well as potential benefits of dose reduction, should be further explored amongst upadacitnib users in larger, prospective studies.

Background While upadacitinib (UPA) is an approved selective Janus kinase 1 inhibitor for moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC), its real-world performance in Chinese patients remains underexplored. This prospective study aims to report real-world data on efficacy and safety of UPA in Chinese patients with inflammatory bowel disease (IBD). Methods This is a single-center, prospective cohort study from the IBD center of Sir Run Run Shaw Hospital. Moderate-to-severe patients with CD and UC who initiated UPA treatment between September 1, 2023, and July 31, 2025 were enrolled. Data on patient characteristics, treatment paradigm, efficacy, and adverse events (AEs) were collected. Results This study enrolled 253 patients (203 CD; 50 UC) with median disease durations of 7.9 and 4.4 years, respectively. All patients were biologic-experienced, with 56.2% of CD and 60.0% of UC having failed ≥2 advanced therapy lines. For CD, at week 12/52, clinical remission rates were 70.3% (123/175) and 68.2% (73/107). Endoscopic remission rates were 34.0% (34/100) and 34.8% (23/66) (Figure 1A). Multivariate analysis identified lower body mess index, higher baseline Crohn’s disease activity index, and third-line advanced therapies as independent factors associated with reduced likelihood of clinical remission at week 12. For UC, clinical remission rates increased from 55.3% (21/38) at week 12 to 90.0% (18/20) at week 52. Endoscopic remission was observed in 66.7% (20/30) and 81.3% (13/16), respectively (Figure 1B). Perianal disease resolution was observed in 47.1% (72/153) in CD. Extraintestinal manifestation (EIM) resolution rates were 77.8% (21/27) in CD and 66.7% (2/3) in UC. Treatment discontinuation rates were 22.7% for CD and 36.0% for UC, primarily due to inadequate response (CD: 16.3%; UC: 12.0%), followed by AEs (CD: 5.4%; UC: 14.0%). Regarding safety, AEs possibly related to UPA occurred in 35.0% (71/203) of CD and 30.0% (15/50) of UC, while severe AEs occurred in17.2% and 18.0%, respectively. The most common AEs were cutaneous manifestations, respiratory reactions, and anemia in CD; and cutaneous manifestations, herpes zoster infection, and opportunistic infections in UC. Conclusion This prospective real-world study validates UPA as a highly effective and well-tolerated treatment option for a predominantly biologic-refractory Chinese IBD population. UPA induced high rates of clinical and endoscopic remission and demonstrated meaningful efficacy in resolving perianal disease and EIMs, thereby addressing core unmet needs. Together with a manageable safety profile, these robust data affirm a favorable benefit-risk profile for UPA in this challenging-to-treat cohort. Reference: Not available. Conflict of interest: Dr. Yao, Lingya: No conflict of interest Xu, Yining: No conflict of interest Xia, Wenhao: No conflict of interest Cao, Qian: No conflict of interest

BackgroundPreviously published short‐term results (week 16) of this trial showed a significant improvement in clinical, radiologic and biochemical outcomes in Crohn's disease patients with therapy‐refractory perianal fistulas after treatment with hyperbaric oxygen therapy.ObjectiveTo assess the long‐term (week 60) efficacy, safety and feasibility of hyperbaric oxygen therapy in perianal fistula in Crohn's disease.MethodsCrohn's disease patients with high perianal fistula(s) failing conventional treatment >6 months were included. Exclusion criteria were presence of a stoma, rectovaginal fistula(s) and recent changes in treatment regimens. Patients received 40 hyperbaric oxygen sessions and outcomes were assessed at week 16 and week 60.ResultsTwenty patients were included (median age 34 years). At week 16, median scores of the perianal disease activity index and modified Van Assche index (co‐primary outcomes) decreased from 7.5 (95% CI 6–9) to 4 (95% CI 3–6, p < 0.001) and 9.2 (95% CI 7.3–11.2) to 7.3 (95% CI 6.9–9.7, p = 0.004), respectively. At week 60, the respective scores remained significantly lower than baseline: 4 (95% CI 3–7, p < 0.001) and 7.7 (95% CI 5.2–10.2, p = 0.003). Perianal disease activity index score of 4 or less (representing inactive perianal disease) was observed in 13 patients at week 16 and 12 patients at week 60. Using fistula drainage assessment, 12 and 13 patients showed a clinical response at week 16 and 60, respectively, and clinical remission was achieved in four patients for both time points. At week 16, a statistically significant biochemical improvement (C‐reactive protein and faecal calprotectin levels) was found, but this effect was no longer significant at week 60.ConclusionsThe clinical and radiologic improvement of perianal fistula in Crohn's disease, that was found at week 16 after treatment with hyperbaric oxygen therapy, is maintained at 1‐year follow‐up.