Introduction

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease (IBD), with mucosal inflammation affecting the rectum (proctitis, E1), left side of the colon (E2), or whole colon (pancolitis, E3). Proctitis is considered a mild disease, and often excluded from clinical trials due to heterogeneity in accessing the affected area of the colon. Proximal extension of the disease is associated with a more severe clinical course. We compared the disease burden of patients with UC according to disease extent.

Aims & Methods

THEFAR is a cross-sectional, observational, multicentre study, including adult patients with UC treated with advanced therapy (AT; biologics or Janus kinase inhibitors). Gastroenterologists across 41 centres included consecutive patients during routine clinic visits. They completed medical and therapeutic management data, including disease activity (partial Mayo score) using an electronic case report form (eCRF). Patients completed self-reported quality of life (EQ-5D-5L), disability (IBD-Disk), incontinence (Wexner score), bowel urgency (Urgency Numeric Rating Scale, UNRS), and Work Productivity and Activity Impairment UC (WPAI:UC) questionnaires.

Results

293 patients with UC (mean age 44 ± 16 years; 50% [147/293] male) were enrolled, with 292 self-reported questionnaires returned for analysis; 45 (15%) patients had proctitis (E1), 117 (40%) left-side colitis (E2), and 131 (45%) extensive colitis (E3). Former smokers were more common in E2 (25%) and E3 (28%) than E1 (11%) subgroups (p=0.01). Comorbidities, including chronic rheumatological disease and cardiovascular diseases, were similar across all subgroups (p>0.05). Disease duration was related to the extent of disease: mean duration of 5.3 years (E1) to 8.8 years (E3) (p=0.02). Age at diagnosis was lowest in E3 (33 years) compared to E1 and E2 (38 years each) subgroups (p=0.02). Regardless of subgroup, there was a similar incidence of flares over the past year, presence of extra-intestinal manifestations, and disease activity per partial Mayo score (all p>0.05). There was no proof of difference in current treatment allocation, duration or lines of advanced therapies, or corticosteroid use (p>0.05 for all [except golimumab]) between subgroups. The proportions of hospitalized patients were significantly different in subgroups: E1 (11%), E2 (21%), and E3 (46%) (p<0.0001).
There was no between-group difference for EQ-5D-5L, IBD-Disk, or WPAI:UC scores (all p>0.05). UC-related patient-reported outcomes were similar across subgroups according to both the Wexner score (p>0.05) and UNRS (p>0.05; Table).

Conclusion

In this cohort of patients with UC treated with AT, there was no association between the extent of disease and quality of life, disability, treatment allocation, work impairment, incontinence, or bowel urgency. However, the extent of disease was associated with hospitalizations. Patients with proctitis treated with AT experience similar disease burden and require a comparable level of treatment as those with left-sided colitis and pancolitis.
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Disclosure

M.F. has received lecture/consultant/travel support fees from Abbvie, MSD, Ferring, Tillots, Takeda, Sandoz, Fresenius, Arena, Pfizer, Amgen, Biogen, Gilead, Galapagos, Janssen
V.G., I.R., and I.J. are employees and minor shareholders of Eli Lilly and Company Ltd.
N.E. is an employee and minor shareholder of Eli Lilly and Company Ltd and reports previous employment and minor shareholdings with AbbVie and Gliead Science.
R.A. has no conflicting interests to declare.

Introduction

Upadacitinib, a selective JAK inhibitor, is approved for moderate-to-severe Crohn’s disease (CD). However, real-world data on its effectiveness and safety, particularly in highly refractory populations, remain scarce. The UPITA-Crohn registry was established to evaluate the outcomes of upadacitinib in clinical practice across multiple centers in Andalusia, Spain.

Aims & Methods

This ambispective, multicenter registry included 142 patients with refractory CD treated with upadacitinib in 12 Andalusian hospitals. Clinical and biochemical data were collected at baseline, weeks 12 and 16, and at 6 months. Clinical remission (CR) was defined as a Harvey-Bradshaw Index (HBI) <5; clinical-biochemical remission (CBR) as HBI <5, CRP <5 mg/L, and fecal calprotectin <250 μg/g; and steroid-free remission (SFR) as HBI <5 without corticosteroids from week 12. Outcomes were also analyzed overall and according to prior exposure to advanced therapies.

Results

The UPITA-Crohn registry cohort included 142 patients with refractory Crohn’s disease. The mean age was 40.8 years (range 18–76), with 40% male. The mean disease duration at the time of upadacitinib initiation was 13.3 years (range 1–42), with a mean of 2.7 failed advanced therapies, highlighting a population with longstanding and complex disease. Most patients had ileocolonic involvement (50%), 22% had perianal disease, and 32% had previously undergone resective surgery.
The majority (74.4%) received induction with upadacitinib 45 mg for 12 weeks. At week 12, clinical remission was achieved by 54% of patients, with 15% reaching clinical-biochemical remission. At 6 months, among those still on treatment, 48.3% maintained clinical remission, 16.1% achieved clinical-biochemical remission, and 18.4% achieved steroid-free remission (Table 1).
When stratified by prior therapy, 6-month clinical remission was similar between patients with ≥2 prior advanced therapies (48.5%) and those with only 1 prior therapy (47.4%), with no significant difference. Steroid-free and clinical-biochemical remission rates were also slightly higher among less refractory patients, but differences were modest.
A total of 31 patients (21.8%) discontinued upadacitinib before 6 months, mainly due to primary non-response (70.9%). Adverse events were reported in 21.1% of patients, most commonly infections (9 cases), acne (7), transient transaminase elevation (5), and herpes zoster (2). Seven discontinuations were due to serious adverse events, including thrombosis, stroke, myocardial infarction, fever, and severe infections.

Table 1: Effectiveness Outcomes

Conclusion

Upadacitinib demonstrated meaningful effectiveness and a manageable safety profile in a real-world cohort of refractory Crohn’s disease patients. Notably, clinical remission rates remained stable even in those with multiple prior advanced therapies, suggesting upadacitinib may be a valuable option for patients with limited alternatives.

Introduction

Upadacitinib (UPA) is an oral, reversible Janus kinase inhibitor (JAKi) approved for the treatment of patients with moderate-to-severe ulcerative colitis (UC).^1-2 Despite substantial evidence from clinical trials supporting the use of UPA for treating UC, real-world (RW) data on its effectiveness and safety remain limited.³ The Prospective Real-World Study of UPA in UC (PROFUNDUS) is an ongoing multi-country, open-label, noninterventional, observational study aimed to evaluate the effectiveness and safety of UPA in patients with moderate-to-severe UC in RW practice (initiated 15 Aug 2022).

Aims & Methods

PROFUNDUS recruited 785 adult patients (18 to 75 years [yrs] of age) with moderate-to-severe UC initiating UPA in 16 countries worldwide. UPA was administered in accordance with the terms of the local marketing authorization, with patient treatment determined by the investigator, and patients followed for up to 3 yrs (156 weeks [wk]). This analysis represents data available after the first 500 patients completed 6 months of treatment or discontinued before 6 months, with a data cut-off of 28 Feb 2025. Of the first 500 patients who provided informed consent and met the inclusion criteria, the full analysis set (FAS) included 490 patients who initiated a once-daily UPA dosing regimen. This analysis reported baseline demographics and disease characteristics among FAS; the time to achievement of first clinical response per daily Partial Adapted Mayo Score (pAMS) and the percentage of patients achieving clinical response per pAMS at the end of UPA induction (wk 8) or extended induction (wk 16) were reported among evaluable patients who took at least 1 dose of UPA and had available scores to define the outcomes, a subset of FAS. Safety outcomes were analysed through week 26 (6 months), with treatment-emergent adverse events (TEAEs) presented as patient numbers and percentages.

Results

Among FAS, the patient age range was 18 to 79 yrs; 43.3% were female. At baseline (defined as the last available assessment on or before the first dose date of UPA), pAMS were as follows: < 2: 26.5%; 2-4: 48.1%; > 4-5: 18.8%; > 5-6: 6.6%; with score 0 indicative of inactive disease, while a score of 6 indicates active disease and spontaneous bleeding.⁴ At baseline, 51.3% of patients had a history of intolerance or inadequate response (IR) to advanced therapies (AT-IR), with 13.1% of patients who failed ≥ 1 JAKi. Among evaluable patients, the median (IQR) time to achieve the first clinical response per daily pAMS was 4 (3.0-8.0) days (N = 373; Table). By the end of induction treatment (wk 8 or 16), 79.6% (258/324) of the evaluable UPA-treated patients achieved clinical response per pAMS (Table). Among UPA-treated patients, the occurrence rates of any treatment-emergent adverse events (TEAEs) and TEAEs possibly related to the study treatment were as follows: any adverse event (AE) (51.2%; 34.9%), serious AEs (5.5%; 2.2%), and severe AEs (5.1%; 2.2%) (Table).

Conclusion

In this interim analysis of the PROFUNDUS study, UPA demonstrated rapid effectiveness in achieving clinical response in patients with moderate-to-severe UC in RW practice, in a wide variety of age ranges, consistent with the efficacy observed in the UPA UC clinical trials.¹ Overall, UPA was well-tolerated, with few serious AEs reported, and most of these were assessed as unrelated to UPA by the investigator.

References

1. AbbVie Inc. RINVOQ (Upadacitinib) [package insert] U.S. Food and Drug Administration website. https://www.rxabbvie.com/pdf/rinvoq_pi.pdf. Revised May 2023. Accessed 25 Feb 2025.
2. AbbVie DG& CoK. RINVOQ. Summary of Product Characteristics. European Medicine Agency website. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf. Revised Feb 2025. Accessed 25 Feb 2025.
3. Seidelin J, et al. J Crohn’s Colitis. 2025;19(1):i1260-i1262. [Abstract].
4. Louis E, et al. JAMA. 2024;332(11):881-897.

Disclosure

Funding: AbbVie funded this study (PROFUNDUS; NCT05494606) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.
Acknowledgments: AbbVie and the authors thank the participants, study sites, and investigators who participated in this clinical trial. Paulette A. Krishack, PhD, of AbbVie, provided medical writing support.
Disclosures: Remo Panaccione has received consulting fees, speaker fees, and research support from Abbott, AbbVie, Abbivax, Alimentiv Amgen, AnaptysBio, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen Pharmaceuticals, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Sanofi, Satisfai Health, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB.
Gareth Parkesreports personal payments, honoraria, speaker fees, travel grants and/or fellowships from AbbVie, Allergan, Bristol Myers Squibb, Celltrion, Ferring, Galapagos, Janssen, Napp, Takeda, and Tillotts, and directorship and shareholding with Ampersand Health. TR reports personal grants from AbbVie; personal consulting fees from AbbVie, Arena, Aslan, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, MonteRosa, Mylan, MSD, Novartis, Numab, Pfizer, Roche, Sandoz, Takeda, UCB and XAP; membership of the ECCO Scientific Committee, and membership in the UEG Scientific Committee; director of Endoread.
Mathurin Fumery has received lecture and consulting fees from AbbVie, Amgen, Biogen, BI, BMS, Celgene, Celltrion, CTMA, Ferring, Fresenius, Galapagos, Gilead, Janssen, Pfizer, Lilly, MSD, Sandoz, Takeda, Tillots, and Viatris.
Dominik Bettenworth is on the advisory board or consultant for Amgen, AbbVie, Dr. Falk Foundation, Ferring, MSD, Pfizer, Pharmacosmos, Roche, Takeda, Tillotts Pharma, and Vifor. Silvio Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grünenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor.
Pierre A Morisset, Madhuja Mallick, Shirley H. Chen, and Smitha Suravaram are employees of AbbVie and may own stock options.

Introduction

Inflammatory Bowel Diseases (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC), pose significant global health challenges. Nutrient deficiencies and malnutrition are common in both forms of the disease. Dietary supplementation with TGF-β has been suggested to enhance patients’ nutritional status, quality of life, and improvement of the symptoms. However, comprehensive evaluations of its clinical impact are needed.

Aims & Methods

This study aims to assess the efficacy of nutritional supplementation in improving clinical outcomes, nutritional status, quality of life, fatigue, disability, and body image among IBD patients.
Methods: Multicenter longitudinal study, enrolling 42 IBD patients in clinical activity and/or at nutritional risk. Patients received the nutritional supplement enriched with TGF-β and underwent assessments before supplementation (M0), at 30 days (M30), and at 60 days (M60) of supplement use. Clinical parameters, disease activity (Harvey-Bradshaw score for CD and partial Mayo score for UC), nutritional evaluation, body composition, presence of fatigue, anxiety and depression, disability, and body image were evaluated. Statistical analyses included descriptive statistics and ANOVA (p<0.05).

Results

42 patients were included: 30 (71%) with CD and 12 (29%) with UC; 48% women, age of 35.1 ± 15.65 years. Among CD patients, 30% were in remission, 16.67% had mild, 43.33% moderate, and 10% severe activity. According to Montreal classification, 36.67% presented ileocolonic disease, 36.67% fistulizing behavior, 26.67% stenosing behavior, 33.33% perianal disease. For UC patients, 41.67% had mild and 58.33% moderate activity; 41.67% presented pancolitis. All patients presented malnutrition or nutritional risk at enrollment. Significant improvements were observed in HBI score comparing M0 (7.97±5.70) vs M30 (4.61±3.16) vs M60 (3.27±1.75), p=0.0055. There was also an improvement of the number of bowel movements (5.45±4.65 vs 2.90±2.02 vs 2.65±1.55). Nutritional assessment revealed a significant increase in brachial circumference (24.23±3.68 vs 25.37±3.51 vs 26.03±4.10, p=0.0182). Fatigue decreased (40.58±14.07 vs 33.12±15.72 vs 30.38±14.88, p=0.0293), as well as disability (51.14±25.34 vs 36±20.89 vs 30.33±22.64, p=0.0032). It was observed an improvement of IBD score (135.08±38.88 vs 145.20±48.27 vs 152.71±58.96; p=0.3737) and body image (10.78±7.37 vs 9.68±8.42 vs 5.57±6.04; p=0.1395), with no significance.

Conclusion

Nutritional supplementation demonstrated notable improvements in clinical and nutritional parameters, as well as reduction in fatigue and disability, underscoring its potential as an adjunctive therapy for IBD management

Introduction

Features and management of post operative recurrence (POR) of Crohn’s Disease (CD) after ileocecal resection (ICR) are well defined, but POR after colectomy is scarcely described.

Aims & Methods

Multicenter, nationwide, retrospective study promoted by the Spanish Working Group on Crohn's and Colitis (GETECCU). CD patients who underwent segmental colectomy (SC) or subtotal colectomy (STC) between 2012 and 2023 were included. Primary endpoint was clinical POR, defined as CD-related symptoms requiring salvage therapy despite POR prophylaxis. Secondary endpoints included endoscopic POR (anastomotic and/or perianastomotic CD-associated lesions at endoscopy), association between clinical and endoscopic POR, comparison of clinical and endoscopic POR-free survival among different types of colectomy, surgical recurrence (need for reoperation) depending on colectomy subtypes; and identification of factors associated with post-colectomy POR.

Results

224 patients were included: 157 (70%) underwent SC and 67 (30%) underwent STC. In the SC group, patients were older [44 (SD 15) vs 39 (SD 14) years old, p=0.01] and B3 phenotype was more frequent [68/157 (43%) vs 14/67 (21%), p = 0.003]. POR prophylaxis was prescribed in 119/157 (76%) SC patients and in 47/67 (70%) STC patients, with no significant differences regarding the choice of agent (main baseline characteristics of the study population are described in Table 1). The main indication for surgery was stenosing disease [both in SC group (83/157, 53%) and STC group (34/67, (51%)]. Median follow-up was 19.5 [3.7–67.9] months to clinical POR and 14.0 [5.9–54.1] months to endoscopic POR. Clinical POR developed in 60/157 (38%) in the SC group and 42/67 (63%) in the STC group (p = 0.001). Endoscopic evaluation was available in 190/224 patients (85%) [131/157 SC (83%) and 59/67 (88%) STC]; endoscopic POR was detected in 66/131 (50%) SC patients and 42/59 (71%) STC patients (p=0.012). Among patients with endoscopic POR, 76/108 (70%) also presented clinical POR: 43/66 (65%) patients in the SC group and 33/42 (79%) in the STC group (p=0.203). Clinical and endoscopic POR-free survival was higher for SC than for STC (p log-rank <0.05). Surgical recurrence occurred in 17/157 patients (11%) in the SC group and in 8/67 patients (12%) in the STC group (p=0.992). Multivariate stepwise Cox proportional hazards regression showed significant association of STC, smoking and myenteric plexitis with both clinical POR (HR 2.36, 95%CI [1.45 - 3.82]; HR 1.34, 95%CI [1.03 - 1,75] and HR 1.71, 95%CI [1.01 - 2.91] respectively) and endoscopic POR (HR 2.47, 95%CI [1.49 - 4.10], HR 1.36, 95%CI [1.03 - 1.79] and HR 1.83, 95% CI [1.01 - 3.29], respectively); and immunomodulator prophylaxis with endoscopic POR (HR 1.72, 95%CI [1.02 - 2.90]) (all p-values <.05).

Conclusion

POR remains common after colectomy in patients with CD. Clinical and endoscopic POR rates are higher following STC compared to SC in patients under similar prophylactic regimes. Although prospective research is still warranted, our data support favoring segmental resection of colonic CD when feasible.

Disclosure

J.L.R.G. has received financial support for traveling and educational activities or has received fees as a speaker from Abbvie, Kern Pharma, Janssen, Takeda, Pfizer, Lilly, Galapagos, Adacyte, Ferring, Tillotts Pharma, Faes Farma, Norgine and Casen. C.S.F. has received financial support for traveling and educational activities or has received fees as a speaker or consultant from Abbvie, Kern Pharma, Lilly, Ferring, MSD, Janssen, Takeda and Tillotts Pharma. YZ has received financial support for travelling and educational activities from or has served as an advisory board member for AbbVie, Adacyte, Alfasigma, Almirall, Amgen, Boehringer Ingelheim, Dr Falk Pharma, Faes Pharma, Fresenius Kabi, Ferring, Galapagos, Janssen, Johnson&Johnson, Kern, Lilly, MSD, Otsuka, Pfizer, Sanofi, Shire, Takeda, and Tillotts Pharma. The rest of the authors have no conflicts of interest to declare regarding this study.