Introduction

The risk of postoperative recurrence (POR) within 1 year after ileocecal resection (ICR) for Crohn’s disease (CD) remains high. Currently, there is no consensus on how to optimally reduce the risk of endoscopic (e)POR, clinical (c)POR or surgical (s)POR.

Aims & Methods

The PORCSE study aims to evaluate the impact of two strategies: early medical prophylaxis (proactive strategy) versus treatment driven by findings at elective endoscopy 6-12 months after ICR (reactive strategy).
A retrospective, observational, multicentric, superiority study was performed including CD patients undergoing first ICR between 2008-2019. Patients were assigned to cohort 1 if prophylactic biological or immunomodulator therapy was administered early after ICR, or to cohort 2 if no postoperative prophylaxis was started and medical treatment was driven by endoscopic findings 6-12 months after ICR. The primary endpoint was the rate of ePOR evaluated at ileocolonoscopy 6-12 months post ICR and was defined as Rutgeerts score >i1. Secondary endpoints were colonic disease activity at first endoscopy, severe ePOR (Rutgeerts i3-i4), cPOR (symptoms leading to restart of therapy), sPOR (repeated surgery or endoscopic balloon dilatation) and differences between participating centres.
Statistical analyses were performed with SPSS v28. Propensity score matching was used for regression analyses.

Results

In total 346 patients were included from 26 centres in 9 European countries. Of these, 47.4% received prophylactic postoperative treatment before postoperative endoscopy (cohort 1) and 52.6% did not (cohort 2). Strategy selection differed significantly between countries (P=0.024). The proactive strategy was preferred in Spain and Portugal whereas the reactive strategy in Belgium, France and Ireland. Although not statistically significant (P=0.143), the same trend was noticed in postoperative metronidazole use.
Patients in cohort 1 had more refractory disease with more upper GI disease, more bio-experienced patients, more penetrating disease phenotype and longer disease duration prior to surgery. Furthermore, metronidazole was more frequently started postoperatively in the proactive cohort (31.7%vs14.3%, P<0.001).
Bivariate logistic regression analyses showed significantly higher odds for ePOR in the reactive treatment group (OR 1.809, 95%CI 1.03-3.18, P=0.039). Furthermore, univariate analyses showed higher rates of colonic disease activity in the reactive group at elective endoscopy 6-12 months after surgery. No significant difference in severe ePOR was found at first endoscopy (OR 1.285, 95%CI 0.60-2.74, P=0.517). After first endoscopy until end of follow-up, patients in the reactive group had significantly higher odds of clinical POR (OR 3.047, 95%CI 1.53-6.08, P=0.002). Surgical recurrence rates were numerically higher in the reactive group (OR 2.586, 95%CI 0.995-6.72, P=0.051) and Cox proportional hazards regression analysis showed a trend towards protective effect of the proactive approach (HR 2.497, 95%CI 0.97-6,40, P=0.057).

Table 1: Demographics and POR

Conclusion

The retrospective PORCSE study provides evidence to support a proactive approach over a reactive approach in terms of prevention of not only endoscopic but also clinical and surgical postoperative recurrence after first ileocecal resection for Crohn’s disease.

Disclosure

Authors have nothing to disclose related to this project

Introduction

The phase 2b GALAXI 1 and phase 3 GALAXI 2&3 studies evaluated guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in participants (pts) with moderately to severely active CD.¹ Pts treated with ustekinumab (UST) who met inadequate response criteria during the long-term extension (LTE) could cross over to GUS 200 mg SC q4w. Here, we present efficacy and safety results in pts who received GUS after experiencing an inadequate response to UST in the pooled GALAXI LTE.

Aims & Methods

Individuals with prior inadequate response or intolerance to UST were excluded from GALAXI; however, during the LTE, pts treated with UST 90 mg SC q8w who met inadequate treatment response criteria (not in clinical response [≥100-point reduction in CDAI score from baseline or CDAI<150] and CDAI ≥220) between Wks 52-80 of LTE were eligible for a treatment switch to GUS 200 mg SC q4w, without IV induction. Clinical response and clinical remission (CDAI<150) were both assessed 16 weeks after treatment switch. Endoscopic response (≥50% improvement from baseline SES-CD or SES-CD≤2) and endoscopic remission (SES-CD≤4 and ≥2-point reduction from baseline and no subscore >1 in any individual component) were assessed at Wk 96. Safety was assessed through Wk 96.

Results

In total, 80 pts treated with UST underwent treatment switch to GUS 200 mg SC q4w maintenance therapy due to meeting inadequate treatment response criteria between Wks 52-80 of the LTE. Of these 80 pts, 75 were included in the efficacy analyses (baseline mean age, 35.2yrs; male, 64.0%; mean CD disease duration, 8.21yrs; mean CDAI, 291.5; mean SES-CD, 12.8; history of inadequate response/intolerance to biologics [BIO-IR], 60.0%).
The proportions of pts achieving clinical response and clinical remission 16 weeks after treatment switch from UST to GUS 200 mg SC q4w were 61.3% and 52.0%, respectively. These results were comparable to the proportions of pts treated with GUS 200 mg IV q4w induction in the BIO-IR subgroup of the total LTE population who achieved clinical response and clinical remission at Wk 12 (61.7% and 46.7%, respectively).
The proportions of pts achieving endoscopic response and endoscopic remission at Wk 96 (ie, ~1 year after treatment switch from UST to GUS 200 mg SC q4w) were 49.3% and 30.7%, respectively. These results were similar to the proportions of pts in the BIO-IR subgroup receiving GUS 200 mg SC q4w maintenance who achieved endoscopic response and endoscopic remission at Wk 48 (57.2% and 35.5%, respectively).
Safety results are summarized in the Table.

Table. Safety Summary From Treatment Switch Through Week 96

Conclusion

Among pts who experienced inadequate response to UST in the LTE, more than half achieved clinical remission 16 weeks after treatment switch to GUS 200 mg SC q4w, and approximately 50% were in endoscopic response ~1 year after treatment switch. These data suggest pts with an inadequate treatment response to UST may benefit from GUS treatment. Results should be interpreted considering that pts received GUS SC maintenance therapy directly without IV induction. Key safety event rates were consistent with the known safety profile of GUS in approved indications.

References

1) Sachen K, Hammaker D, Sarabia I, et al. Frontiers in Immunology. 2025; doi:10.3389/fimmu.2025.1532852.

Disclosure

AA reports potential conflicts of interest with AbbVie, Bristol Myers Squibb/Celgene, DiaSorin, Eli Lilly, Gilead, IBD Horizons, Janssen, Pfizer, Takeda, and TLL Pharmaceuticals
DW reports consulting fees from AbbVie, Bristol Myers Squibb, Janssen, Lilly, Pfizer, Takeda
RL reports having received advisory board fees from AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, and Takeda; received research grants from Celltrion, Shire, Janssen, Takeda, Joanna Tiddy grant from University of Sydney, McCusker Charitable Trust, Gastroenterological Society of Australia, NHMRC, Gutsy Group, and Pfizer
RVR, WvD, and CB are employees of Johnson & Johnson and own company stock/stock options.
TH received grant support from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd., consulting fees from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer Inc., Nichi-Iko Pharmaceutical Co. Ltd., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, and lecture fee from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc. Kissei Pharmaceutical Co. Ltd.
JP reports consultancy fees/honorarium from AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman, and has served on a data safety monitoring board for Alimentiv, Mirum, Sorriso, Sanofi, and Surrozen.

Introduction

Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The safety of tofacitinib was evaluated in the Overall Cohort, which consisted of 6 studies: 4 randomised, placebo-controlled Phase (P)2/3 studies (NCT00787202; NCT01465763; NCT01458951; NCT01458574), an open-label, long‑term extension study (NCT01470612) and a randomised P3b/4 study (NCT03281304). We report final safety analyses from the tofacitinib UC clinical programme of ≤9.2 years of tofacitinib exposure (cut off date: 18 April 2022).

Aims & Methods

This analysis included 1157 patients (pts) receiving tofacitinib 5 or 10 mg twice daily (BID; predominant dose [PD]) in the Overall Cohort and a previously reported 52-week Maintenance Cohort.^1,2 Proportions and incidence rates (IRs; unique pts with events/100 pt-years of exposure) were evaluated for deaths and adverse events of special interest (AESI): serious infections; herpes zoster (HZ); opportunistic infections (OIs); malignancies (excluding non‑melanoma skin cancer [NMSC]); NMSC; major adverse cardiovascular events (MACE); deep vein thrombosis (DVT); pulmonary embolism (PE); and gastrointestinal (GI) perforations.

Results

In the Overall Cohort, 1157 pts received ≥1 dose of tofacitinib 5 or 10 mg BID; 938 (81.1%) received a PD of 10 mg BID; 552 (47.7%) pts had received tofacitinib for ≥2 years. Median treatment duration was 1.7 years (mean 2.8; range 0.0–9.2). IRs (95% CI) for all tofacitinib in the Overall Cohort (Table): deaths 0.24 (0.10, 0.48); serious infections 1.80 (1.37, 2.32); HZ (non-serious and serious) 3.24 (2.63, 3.94); serious HZ 0.24 (0.10, 0.48); OIs 0.96 (0.65, 1.36); malignancies (excluding NMSC) 0.88 (0.59, 1.26); NMSC 0.71 (0.45, 1.07); MACE 0.27 (0.12, 0.52); DVT 0.06 (0.01, 0.22); PE 0.18 (0.07, 0.40); and GI perforations 0.09 (0.02, 0.27).

Conclusion

IRs for AESI remained stable over an extended period of time (≤9.2 years) with the inclusion of the P3b/4 final data and were consistent with prior Overall Cohort analyses (≤7.8 years).^1,2 The safety profile of tofacitinib in the UC clinical programme was consistent with that observed in other indications.^3,4

References

1. Sandborn WJ et al. Clin Gastroenterol Hepatol 2019;17:1541–50.
2. Sandborn WJ et al. J Crohns Colitis 2023;17:338–51.
3. Cohen SB et al. RMD Open 2020;6:e001395.
4. Burmester GR et al. Drug Saf 2020;43:379–92.

Disclosure

Julian Panés has received grants and/or research support from AbbVie and Pfizer Inc, is a member of the speakers’ bureau for Abbott, Ferring, Janssen, Pfizer Inc and Takeda, has been an advisory board member for AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celsius, Celltrion, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer Inc, Progenity, Prometheus, Protagonist, Revolo, Robarts, Sanofi, Takeda, Theravance and Wasserman, and has developed educational presentations for AbbVie, Janssen, Pfizer Inc, Roche and Takeda. Geert R. D’Haens has received speaker fees from AbbVie, Boehringer Ingelheim, Celltrion, Johnson & Johnson, Pfizer Inc, Takeda and Tillotts, and has been an advisory board member for AbbVie, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Cosmo, Eli Lilly, Galapagos, GlaxoSmithKline, Johnson & Johnson, Takeda, Pfizer Inc, Polpharma, Prometheus, Tillotts and Ventyx. Bruce E. Sands has acted as a consultant for, or received speaker fees from, AbbVie, Abivax, Adiso Therapeutics, Alimentiv, Amgen, Arena, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly, Entera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead Sciences, Genentech, GlaxoSmithKline, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kallyope, Merck, MiroBio, Morphic, MRM Health, OSE Immunotherapeutics, Pfizer Inc, Progenity, Prometheus, Protagonist, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic Operating Company, Takeda, Target RWE, Theravance, TLL Pharmaceutical, USWM Enterprises, Ventyx and Viela Bio, and is a shareholder of Ventyx. Siew C. Ng has received grants and/or research support from AbbVie, Ferring, Janssen and Olympus, has received speaker fees from AbbVie, Ferring, Janssen, Menarini, Pfizer Inc, Takeda and Tillotts, has been an advisory board member for AbbVie, Ferring, Janssen and Pfizer Inc, holds a Directorship with Microbiota I Center, and is the scientific co-founder and a shareholder of GenieBiome Limited. Nervin Lawendy is an employee and shareholder of Pfizer Inc. Nicole Kulisek is an employee and shareholder of Pfizer Inc. Xiang Guo is an employee and shareholder of Pfizer Inc. Joseph Wu is an employee and shareholder of Pfizer Inc. Ivana Vranic is an employee and shareholder of Pfizer Inc. Remo Panaccione has received grants and/or research support from AbbVie, Janssen, Pfizer Inc, and Takeda, and has acted as a consultant for and/or received speaker fees from Abbott, AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos, Eisai, Elan, Eli Lily, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion, Pendopharm, Pfizer Inc, Progenity, Prometheus, Protagonist, Roche, Sandoz, Satisfai Health, Shire, Sublimity, Takeda, Theravance, Trellus, Viatris and Ventyx. Séverine Vermeire has received grants from AbbVie, Galapagos, MSD, Pfizer Inc, and Takeda, has acted as a consultant for AbbVie, AbolerIS Pharma, Alimentiv, Arena, AstraZeneca, Avaxia, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CVasThera, Dr Falk Pharma, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead Sciences, Hospira, IMIdomics, Janssen, Johnson & Johnson, Materia Prima, MiroBio, Morphic, MRM Health, MSD, Mundipharma, Pfizer Inc, ProDigest, Progenity, Prometheus, Robarts, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts and Zealand, and has received speaker fees from AbbVie, Dr Falk Pharma, Ferring, Hospira, MSD, Takeda and Tillotts.

Introduction

The Epi-IBD cohort is a prospective European population-based cohort of 1,390 patients diagnosed in 2010 and 2011 with inflammatory bowel disease (IBD) according to Copenhagen criteria in centres from Eastern and Western European countries.

Aims & Methods

The study aims at describing differences in incidence, treatment strategies, disease course and prognosis of Crohn’s disease (CD) across Eastern and Western Europe. CD patients were followed prospectively from the time of diagnosis until December 31^st, 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment, were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org. Associations between surgery and covariates were analysed by multivariate Cox regression analyses.

Results

In total, 482 CD patients aged ≥15 years from 21 centres in 5 Eastern and 11 Western European countries were included. At 10-years follow-up, 101 (21%) patients underwent first intestinal resection and 11 out of these 101 patients (11%) underwent additional resections. Furthermore, 176 (37%) patients had at least one CD related hospitalization. Cancer was diagnosed in 21 (4%) patients, including 4 gastrointestinal cancers. The use of IBD medication was comparable between Eastern and Western European centres apart from 5-aminosalicylic acid agents (Table 1).
During follow-up, 60 out of 360 patients (17%) progressed from non-stricturing-non-penetrating disease (B1) at diagnosis to stricturing or penetrating disease (B2 or B3) while 13 out of 83 patients (16%) with stricturing disease (B2) progressed to penetrating disease (B3). The median time to progression was 28 (IQR: 9-64) months from diagnosis. No patients from Eastern Europe were exposed to biological therapy prior to change in behaviour, compared to 23 out of 66 patients (35%) from Western Europe.
Multivariate Cox regression analysis showed no difference in risk of surgery according to European region (Eastern vs. Western Europe, HR: 0.54, 95%CI: 0.24-1.21). Early intervention with biological therapy (within 6 months) did not influence the risk of surgery (HR:0.75, 95%CI: 0.31-1.83), however early introduction of immunomodulators reduced the risk significantly (HR:0.54, 95%CI: 0.30-0.98). Progression in behaviour from B1 was associated with higher risk of surgery (HR:7.62, 95%CI: 3.91-14.87).

Conclusion

After 10 years of follow-up, 21% underwent intestinal resection and 10% required additional resections. Despite the widespread use of immunomodulators and biological therapy, 16% of the patients had disease behavioural progression, which was associated with higher risk of surgery. Early introduction of immunomodulators was found to be beneficial.