BACKGROUND AND AIMS:Vedolizumab has become the preferred first-line advanced therapy in ulcerative colitis (UC). However, the optimal second-line treatment following vedolizumab failure remains unclear. We aimed to evaluate the effectiveness and safety of second-line therapies after first-line vedolizumab. METHODS:We conducted a multicenter retrospective study including UC patients from 31 centers who received infliximab (IFX), subcutaneous (SC) anti-TNFs, or ustekinumab after vedolizumab failure. The primary endpoint was steroid-free clinical remission (SFCR) at week 14. Predictors of remission were identified using multivariate logistic regression. RESULTS:Among 196 patients, 99 received IFX, 27 anti-TNF SC, and 70 ustekinumab. At week 14, SFCR was achieved in 78 patients (39.8%): 38 (38.4%) with IFX, 8 (29.6%) with anti-TNF SC, and 32 (45.7%) with ustekinumab, with no significant difference between groups (p = 0.32). Median treatment persistence ranged from 8 to 9.2 months. Baseline corticosteroid use was associated with lower odds of SFCR (OR = 0.37, 95% CI [0.18-0.73]). Adverse events occurred in 15.8% of patients, including 12.2% serious events. Overall adverse events were less frequent with ustekinumab than with IFX (10.0% vs. 24.2%, p = 0.02), while serious events were comparable (5.7% vs. 16.1%, p = 0.08). Discontinuation due to adverse events was more frequent with IFX (12.1%) and anti-TNF SC (14.8%) than with ustekinumab (2.9%, p = 0.045 and 0.049). CONCLUSION:In UC patients failing vedolizumab, second-line IFX, anti-TNF SC, and ustekinumab showed similar effectiveness and persistence. Infliximab remains a robust option for rapid control in high inflammatory burden, whereas ustekinumab may be preferred for its superior safety profile in high-risk patients.

INTRODUCTION:Chronic intestinal pseudo-obstruction (CIPO) is a rare, heterogeneous disorder associated with severe morbidity. Genetic variants and histopathological lesions have been described, but their combined evaluation has rarely been assessed in adult CIPO cohorts. This study aimed to evaluate the contribution of integrated genetic and histological analyses in adults with CIPO. METHODS:We conducted a retrospective observational study of adults with CIPO followed at a national tertiary referral center. Patients with CIPO underwent genomic profiling, including next-generation sequencing (NGS) panel, long-range polymerase chain reaction (PCR), whole-exome, and whole-genome sequencing. Centralized histological analysis of full-thickness bowel biopsies and resections was integrated with genomic data to assess their combined impact on disease outcomes. RESULTS:The cohort included 130 patients (75 females, 55 males, aged 19-74 years), followed for up to 64 years. Genetic and histological analyses characterized 82% of the patients (genetic diagnosis: n = 65/112, 58%; histological diagnosis: n = 73/96, 76%), allowing the classification of patients into 6 groups: monogenic myopathy (n = 42), mitochondriopathy (n = 19), unspecified myopathy (n = 26), autoimmune myopathy (n = 8), neuropathy (n = 9), and others (n = 26). Survival and postoperative outcomes differed across groups. In this cohort, patients with monogenic myopathy had the most favorable long-term survival (adjusted hazard ratio: 0.06, 95% CI: 0.01-0.42; P = 0.004) and higher rates of improvement after bowel resection compared with other patients. DISCUSSION:Integrated genetic and histological evaluation informed etiological classification in adults with CIPO and may aid clinical decision-making.

INTRODUCTION:Upadacitinib (UPA) is effective for treating luminal Crohn's disease (CD), but data on perianal CD (pCD) remain limited. METHODS:All consecutive patients with active pCD (primary and/or secondary lesions) treated with UPA across 13 French centres between September 2022 and August 2025 were included in a retrospective cohort study. Clinical remission was defined as absence of fistula drainage (spontaneous or on gentle pressure) and healing of anal ulcerations without initiation of new therapy. Clinical response was defined as ≥ 50% improvement in fistulas and/or ulcerations based on physician assessment. Clinical outcomes were analysed using non-responder imputation, and magnetic resonance imaging (MRI) outcomes as observed. RESULTS:Among the 59 patients included, 43 (73%) had fistulizing pCD and 16 (27%) isolated anal ulcerations. All patients were previously exposed to at least one biologic and 79% of those with fistulizing pCD underwent prior perianal surgery. In patients with fistulizing pCD, clinical remission was achieved in 11/43 (26%) and 11/43 (26%) patients at 6 and 12 months, respectively, clinical response in 21/43 (49%) and 13/43 (30%) patients. At 12 months, MRI response was documented in 9/13 (69%) and MRI remission in 1/13 (8%) patients with fistulizing pCD. Among patients with fistulizing pCD, no factors predicted clinical remission. Among patients with isolated anal ulcerations, complete healing occurred in 5/16 (31%) at 3 months, 4/16 (25%) at 6 months and 4/16 (25%) at 12 months. CONCLUSION:In this real-world cohort of refractory pCD, UPA achieved clinical remission in one-quarter of patients at 1 year.

Upadacitinib has demonstrated efficacy for induction and maintenance therapy in luminal Crohn’s disease (CD) (1). According to a post-hoc analysis of a phase 3 randomized controlled trial, upadacitinib also showed benefit in the treatment of fistulizing perianal CD (2). However, its real-world effectiveness in this specific phenotype has not yet been evaluated. All consecutive patients with active perianal CD (primary and/or secondary lesions) treated with upadacitinib across 13 French centres between September 2022 and August 2025 were included in a retrospective cohort study. Clinical remission was defined as the absence of draining pus including with pressure and healing of anal ulcers and/or fissures, without the addition of new dedicated treatment for perianal lesions (antibiotics and/or topics). Clinical response was defined as improvement of at least 50% of fistulas and/or ulcers by physician’s assessment. MRI-based response and remission were also assessed. Treatment failure was defined as upadacitinib discontinuation, initiation of a new advanced therapy, or need for additional perianal surgery. Patients lost to follow-up were considered as treatment failures. Fifty-nine patients were included: 43/59 (73%) with fistulizing perianal CD and 16/59 (27%) with isolated primary anal ulcerations. Median age was 38 years (interquartile range [29–47]); 29 (49%) were male and 11 (19%) were active smokers. All patients had previously been exposed to at least two biologics (median 4 [3–5]), and 40 (68%) had a history of perianal surgery, including 34/43 (79%) in the fistulizing subgroup. Among patients with fistulizing perianal CD, clinical remission was achieved in 5/43 (12%), 11/43 (26%), and 11/43 (26%) patients at 3, 6, and 12 months, respectively, while clinical response was observed in 27/43 (63%), 21/43 (49%), and 13/43 (30%) patients (Figure 1). At 12 months, MRI response was documented in 9/14 (64%) and MRI remission in 1/14 (7%) patients with fistulizing perianal CD. Among those with isolated anal ulcerations, complete ulcer healing was observed in 4/16 (25%) at 12 months (Figure 1). No clinical or demographic factors were associated with clinical remission at 12 months in univariate analysis. Sixteen adverse events (AEs) were reported in 14 patients (27%), including three (5%) serious AEs corresponding to CD exacerbations. At 12 months, 10 patients (17%) underwent perianal drainage surgery, and 16 (27%) discontinued upadacitinib, all due to lack of efficacy. In this real-world multicentre cohort of patients with refractory perianal CD, treatment with upadacitinib achieved clinical remission in approximately one-quarter of patients at one year. References: (1) Loftus EV, Panés J, Lacerda AP, et al. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med. 2023;388(21):1966-1980. (2) Colombel JF, Lacerda AP, Irving PM, et al. Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn’s Disease: A Post Hoc Analysis of 3 Phase 3 Trials. Clin Gastroenterol Hepatol. 2024;0(0). Conflict of interest: Dr. Richard, Nicolas: Lecture/consultant fees from AbbVie, Amgen, Celltrion, Ferring, Janssen, Lilly, Sandoz and Takeda. Seksik, Philippe: I received personal fees from Takeda, Janssen, Merck MSD, Biocodex, Ferring, Fresenius Kabi, Astellas, Amgen, Pfizer, Pilege and Abbvie Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Laharie, David: Personal Fees: Board, consulting and lecture fees from Abbvie, Alfasigma, Amgen, Biocon, Celltrion, Ferring, Fresenius-Kabi, Johnson & Johnson, Lilly, MSD, Pfizer, Sandoz and Takeda Nancey, Stéphane: board membership and lecturing fees from Abbvie, Takeda, Celltrion Healthcare, Pfizer, Galapagos, Johnson & Jonshon, Lilly, Fresenius, Amgen, Medac, MSD. Coffin, Benoît: No conflict of interest Pelletier, Anne-Laure: •ALP has received lecture/consultant fees from Janssen, Pfizer, and Novartis. Uzzan, Mathieu: Grant: ECCO-IOIBD, Fondation pour la Recherche Medicale (FRM), SNFGE Personal Fees: Abbvie, Takeda, Celltrion, Janssen, Amgen, Alfasigma, Pfizer Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Amil, Morgane: No conflict of interest Vuitton, Lucine: •LV has received fees for lectures and/or consulting fees from Abbvie, Amgen, Johnson & Johnson, Celltrion, Takeda, Pfizer, Lilly, Ferring, MSD, Dr Falk Pharma, Nordic Pharma, Alpha sigma. Fumery, Mathurin: •M.F. has received lecture/consultant fees from AbbVie, Ferring, Tillotts, MSD, Biogen, Amgen, Fresenius, Hospira, Sandoz, Pfizer, Celgene, Gilead, Boehringer, Galapagos, Janssen, and Takeda. N.R. has received lecture/consultant fees from AbbVie, Janssen and Takeda. Bozon, Anne: No conflict of interest

Importance:T-type calcium channels, particularly the Cav3.2 subtype, are involved in pain transduction. Experimental studies and human data suggested that increased T-type channels activity or expression contributes to visceral hypersensitivity in irritable bowel syndrome (IBS), and that their inhibition alleviates pain. Objective:To evaluate the therapeutic potential of ethosuximide, a T-type calcium channel blocker, for IBS-related abdominal pain. Design, Setting, and Participants:This proof-of-concept, multicenter, double-blinded, placebo-controlled randomized clinical trial started in February 2018 and completed in February 2022, with analyses performed between October 2023 and December 2024. Participants were adults meeting Rome IV criteria for IBS, treated in 10 gastroenterology departments in French university hospitals, with abdominal pain intensity rated at least 4 out of 10 during a 7-day run-in period. Interventions:Patients were randomized to receive ethosuximide or placebo daily for 12 weeks. Main Outcomes and Measures:The primary end point was the responder rate, defined as at least 30% reduction in mean abdominal pain intensity associated with a Subject Global Assessment of relief score at least 4 (ie, considerably or completely relieved). Secondary outcomes included safety, IBS symptom severity, and quality of life. Results:Of 161 enrolled patients, 124 were randomized (64 ethosuximide; 60 placebo). The mean (SD) age was 43.7 (14.9) years, 72 (58.1%) were women, the median (IQR) IBS duration was 5.0 (1.4-10.6) years, and the mean (SD) abdominal pain intensity was 6.0 (1.0). In the intent-to-treat analysis, responder rates did not differ significantly between groups (17 of 64 patients [26.6%] for ethosuximide vs 14 of 60 patients [23.3%] for placebo; relative risk, 1.14; 95% CI, 0.61-2.11). Ethosuximide was less well tolerated, with higher discontinuation rates (30 patients [46.9%] vs 13 patients [21.7%]; P = .003) and more adverse events (261 of 463 adverse events reported overall [56.4%] were determined to be caused by ethosuximide; P < .001), most commonly headaches, sleep disturbances, and nausea, compared with placebo. Conclusions and Relevance:In this randomized clinical trial, ethosuximide did not demonstrate efficacy over placebo for the treatment of IBS-related abdominal pain, and was associated with reduced tolerability. These findings do not support the use of ethosuximide for IBS pain management but highlight the need for development of more selective and better-tolerated T-type calcium channel modulators. Trial Registration:ClinicalTrials.gov Identifier: NCT02973542.

T-type calcium channels, particularly the Cav3.2 subtype, are involved in pain transduction. Experimental studies and human data suggested that increased T-type channels activity or expression contributes to visceral hypersensitivity in irritable bowel syndrome (IBS), and that their inhibition alleviates pain. To evaluate the therapeutic potential of ethosuximide, a T-type calcium channel blocker, for IBS-related abdominal pain. This proof-of-concept, multicenter, double-blinded, placebo-controlled randomized clinical trial started in February 2018 and completed in February 2022, with analyses performed between October 2023 and December 2024. Participants were adults meeting Rome IV criteria for IBS, treated in 10 gastroenterology departments in French university hospitals, with abdominal pain intensity rated at least 4 out of 10 during a 7-day run-in period. Patients were randomized to receive ethosuximide or placebo daily for 12 weeks. The primary end point was the responder rate, defined as at least 30% reduction in mean abdominal pain intensity associated with a Subject Global Assessment of relief score at least 4 (ie, considerably or completely relieved). Secondary outcomes included safety, IBS symptom severity, and quality of life. Of 161 enrolled patients, 124 were randomized (64 ethosuximide; 60 placebo). The mean (SD) age was 43.7 (14.9) years, 72 (58.1%) were women, the median (IQR) IBS duration was 5.0 (1.4-10.6) years, and the mean (SD) abdominal pain intensity was 6.0 (1.0). In the intent-to-treat analysis, responder rates did not differ significantly between groups (17 of 64 patients [26.6%] for ethosuximide vs 14 of 60 patients [23.3%] for placebo; relative risk, 1.14; 95% CI, 0.61-2.11). Ethosuximide was less well tolerated, with higher discontinuation rates (30 patients [46.9%] vs 13 patients [21.7%]; P = .003) and more adverse events (261 of 463 adverse events reported overall [56.4%] were determined to be caused by ethosuximide; P < .001), most commonly headaches, sleep disturbances, and nausea, compared with placebo. In this randomized clinical trial, ethosuximide did not demonstrate efficacy over placebo for the treatment of IBS-related abdominal pain, and was associated with reduced tolerability. These findings do not support the use of ethosuximide for IBS pain management but highlight the need for development of more selective and better-tolerated T-type calcium channel modulators. ClinicalTrials.gov Identifier: NCT02973542

IntroductionTechniques for measuring digestive motility are becoming increasingly precise and enable therapeutic interventions. However, while most of these interventions require general anesthesia, there is limited data on the impact of anesthetic agents on these measurements, and no standardized anesthesia protocol currently exists to guide such procedures. Our working group carried out two Delphi processes involving experts in neurogastroenterology and anesthesiology to reach a consensus on which drugs affect these measurements and to establish an anesthesia protocol.MethodTwo expert groups were formed, comprising 13 neurogastroenterology experts from the French Neuro-Gastroenterology Group (GFNG) and 15 full- or associate professors in anesthesia and intensive care. The first Delphi process involved the neurogastroenterologists and aimed to identify which anesthetic drugs influenced digestive pressure measurements. The second Delphi process, involving anesthetists, sought to develop an anesthesia protocol. Each expert indicated their level of agreement with each statement using a 6-point Likert scale. A statement was endorsed when at least 80% of experts agreed with it. The strength of evidence for each statement was evaluated using the GRADE system.ResultsThe Delphi process with neurogastroenterologists was conducted over three rounds and ultimately resulted in 91 amendments. The second Delphi process with anesthetists took place over two rounds and included 28 amendments, leading to the development of an anesthesia protocol.ConclusionTo our knowledge, this work is the first to establish an expert consensus on anesthetic agents that can affect digestive motility measurements and to propose an anesthesia protocol that accounts for the needs of neurogastroenterologists.

Abstract Background While upadacitinib has demonstrated its efficacy as an induction treatment for Crohn’s disease (CD) in two phase 3 randomized, placebo-controlled trials1, real-world data remain limited. Methods From September 2022 to September 2024, all consecutive patients with refractory CD treated with once-daily upadacitinib 45 mg in 30 French and Belgian GETAID centres were retrospectively included. The primary endpoint was steroid-free clinical remission (SFCR) at week 12, defined as a Harvey-Bradshaw Index (HBI) score of < 4. Secondary endpoints included clinical response (decrease of ≥ 3 points in the HBI score and/or an HBI score < 4), clinical remission, biological remission (calprotectin ≤ 250 µg/g, or CRP ≤ 5 if calprotectin was unavailable), endoscopic or radiological (IUS and/or MRI) response, and adverse events (AEs). Results 234 patients were included, all of whom had been previously exposed to at least one biologic (median 4, IQR[3-4]), and 125 (53.9%) had undergone prior intestinal resection (Table 1). At week 12, SFCR was observed in 107 patients (n=107/197, 54%), clinical response in 120 (n=120/190, 63%) and clinical remission in 111 (n=111/197, 56%). Ninety-two (n=92/179, 51%) achieved biological remission and endoscopic or radiological response was observed in 19 (n=19/40, 48%) patients (Figure 1). Respectively 28 (n=28/37, 76%) and 20 (n=20/37, 54%) of patients with articular EIMs achieved clinical response and remission. For cutaneous EIM, clinical response was achieved in 10 patients (n=10/11, 91%), and clinical remission was achieved in nine patients (n=9/11, 82%). In multivariate analysis, body mass index < 18.5 kg/m2 (OR=0.09, 95%CI: 0.01-0.33, p=0.002) and HBI > 7 (OR=0.24, 95%CI: 0.12-0.47, p<0.0001) were associated with lower rates of SFCR at W12 while the number of prior biologics did not influence SFCR (OR = 0.72, 95% CI: 0.35-1.48; p = 0.36). At week 12, 35 (15%) patients discontinued upadacitinib (lack of effectiveness, n=31; AEs, n=2 and other, n=2). CD-related hospitalization was needed in 18 (7.7%) patients, and 4 (1.7%) underwent intestinal resection. Sixty-eight AEs occurred in 61 patients (26%), including 19 serious AEs, corresponding to 18 cases of CD exacerbation and one case of colonic EBV-associated lymphoproliferative disorder. Acne was observed in 25 (10.7%), justifying treatment discontinuation in one (0.4%). Conclusion In this real-world cohort of highly refractory CD patients, upadacitinib induction resulted in a clinical response in about two-thirds of patients and SFCR in half of patients. References 1.Loftus EV, Panés J, Lacerda AP, et al. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med. 2023;388(21):1966-1980.

Abstract Background Subcutaneous (SC) infliximab is efficient and safe in inflammatory bowel diseases (IBD), but no guidelines exist regarding practical modalities of switching from IV to SC infliximab. This study aimed to describe current practice in France, assess patients’ experience, and identify factors associated with higher satisfaction levels. Methods Two questionnaires were created for this nationwide cross-sectional study. Each practitioner completed a physician questionnaire and provided a patient questionnaire to all consecutive patients receiving infliximab (IV or SC) over an 8-weeks period. Factors associated with a higher satisfaction following switch, assessed using a 10 points numerical scale (10=completely satisfied) were explored using a multivariate analysis. Results Among 48 responding physicians, the switch was proposed more readily for patients in deep remission (97.9%), after infusion-related reactions (91.7%), or for cost-saving reasons (52%). Perianal lesions did not discourage the switch (83.3%), contrary to concerns about reduced infusion unit activity (68.9%) and poor adherence (52.1%). The first SC injection was mainly performed instead of the next IV infusion (77.3%). Immunosuppressive therapy was maintained (87.5%) for patients treated with combination therapy, generally for 6 months. Among 241 enrolled patients, 33.6% had switched to SC infliximab including 14 (17.3%) receiving an intensified SC dose immediately after the switch. Most of these patients (13/14) were on IV infliximab ≥ 10mg/kg/8-weekly prior to switch, had Crohn’s disease (13/14), had received IV infliximab for more than 5 years (10/14) and did not receive concomitant immunosuppressive therapy at the time of switch (10/14). Patients who did not switch cited absence of information regarding the SC option (22.0%), concern over altered medical follow-up (15.2%), and fear of disease relapse (11.4%) as most frequent reasons. Among those who switched, the median satisfaction score was 10/10 [8.0-10.0], even in patients immediately switched to optimized SC infliximab (10/10 [9.0-10.0]). The switch was felt as improving disease activity in 43/77 (55.8%) of patients. 60.5% reported no apprehension before SC injection, whereas 16.0% rated their apprehension above 4/10. No serious adverse events were reported; local injection site reactions (erythema or oedema) were reported only in 7.4% of cases. Multivariate analysis showed that patients’ satisfaction was correlated with the duration of prior IV infliximab treatment (p=0.040). Conclusion This nationwide study provides an overview of current physicians’ practices for switching from IV to SC infliximab that could help for editing guidelines and demonstrates high level of patients’ satisfaction after switch.

Abstract Background Upadacitinib has demonstrated efficacy as an induction treatment for Crohn’s disease (CD)1, and a post hoc analysis of phase 3 randomized, placebo-controlled trials has shown its efficacy in perianal fistulizing CD (pCD)2. However, real-world data in this setting remain limited. Methods From September 2022 to September 2024, all consecutive patients with CD treated with once-daily upadacitinib 45 mg in 32 French and Belgian GETAID centres were retrospectively included. Clinical remission (absence of draining pus including with pressure for fistulas and no anal ulcers for primary lesions, as per local physician’s judgement, with no need for new dedicated medical treatment for perianal lesions (antibiotics and/or topics), or surgical treatment) and clinical response (an improvement of at least 50% of ulcers or fistulas by physician’s assessment) were assessed at week 12. Univariate and multivariable analyses were performed to identify predictors of clinical response. Results Among the 243 patients treated, 54 (22.2%) had active perianal Crohn’s disease (pCD) at the time of induction. This group included 43 patients (81.0%) with fistulizing disease and 11 (19.0%) with isolated anal ulcers. Median age was 38 (IQR, 29.0-45.8) years, 28 (51.9%) were men, and 9 (17.0%) were active smokers. All had been previously exposed to at least one advanced therapy (median number: 4, IQR [3-5]), and 25 (47.2%) had undergone prior perianal surgery (Table 1). By week 12, clinical response was achieved in 37 patients (68.5%, n=37/54), and clinical remission in 10 patients (n=10/54, 18.5%). Among patients with fistulizing pCD, 29 patients (67.4%, n=29/43) achieved clinical response, while 6 (14.0%, n=6/43) achieved remission. Among patients with primary perianal CD, complete remission of ulcers was observed in 4 (n=4/11, 36.4%) (Figure 1). In multivariate analysis, penetrating phenotype (OR=14.8, 95%CI: 1.6-381.9, p=0.04) was associated with higher rates of clinical response at W12 while the number of prior biologics did not influence clinical response (OR = 1.63, 95% CI: 0.47-5.79; p = 0.47). Fifteen adverse events (AEs) occurred in 13 (24.1%) patients, including 5 (9.3%) serious AEs, all 5 cases corresponding to CD exacerbation. At week 12, 7 (13%) patients discontinued upadacitinib, all due to lack of efficacy. Conclusion In this real-world cohort of highly refractory CD patients, upadacitinib induction resulted in a clinical response of perianal CD in two-third of patients. References 1.Loftus EV, Panés J, Lacerda AP, et al. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med. 2023;388(21):1966-1980. doi:10.1056/NEJMoa2212728 2. Colombel JF, Lacerda AP, Irving PM, et al. Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn’s Disease: A Post Hoc Analysis of 3 Phase 3 Trials. Clin Gastroenterol Hepatol. 2024;0(0). doi:10.1016/j.cgh.2024.08.032

BACKGROUND:Real-world effectiveness and safety of upadacitinib in patients with Crohn's disease (CD) remain unclear. AIMS:This study aimed to evaluate the effectiveness and safety of upadacitinib in a real-world cohort. METHODS:From September 2022 to June 2024, all consecutive patients with refractory luminal CD treated with once daily upadacitinib 45 mg in 29 French GETAID centres were retrospectively included. The primary outcome was steroid-free clinical remission (SFCR) at week 12, defined as a Harvey-Bradshaw Index (HBI) of < 4. Clinical response (decrease of ≥ 3 points in HBI and/or HBI < 4), clinical remission, biomarker remission, endoscopic and/or radiologic response and safety were also assessed. RESULTS:Among the 223 patients included, all were previously exposed to at least one biologic (median 4, IQR [3, 4]) and 119 (53.8%) had prior intestinal resection. At week 12, SFCR was achieved in 107/197 (54%), clinical response in 129/197 (65%) and clinical remission in 111/197 (56%). A total of, 90 out of 173 (52%) achieved biomarker remission. Endoscopic and/or radiologic response was observed in 18/38 (47%) patients. Clinical response of extraintestinal manifestations was observed in 37/47 (79%) patients and clinical remission in 29/47 (62%). A total of, 65 adverse events (AEs) occurred in 58 patients (26%), including 17 serious AEs, 16 disease exacerbation and one case of colonic EBV-associated lymphoproliferative disorder. Acne was reported in 24/223 (11%) patients. CONCLUSION:In this real-world cohort of highly refractory CD patients, upadacitinib induction resulted in a clinical response in about two-thirds of patients and in SFCR in half of the patients, with an acceptable safety profile.

Les opioïdes sont efficaces pour la douleur aiguë et chronique, ce qui en fait une option thérapeutique importante en cancérologie pour les soins de support. Ils induisent souvent des effets indésirables digestifs, notamment la constipation induite par les opioïdes (CIO), en raison de leur action sur les récepteurs μ du tube digestif, qui régulent la motricité et les sécrétions. La CIO est le symptôme digestif le plus courant et, bien que longtemps négligée, elle peut sérieusement altérer le confort des patients, au point de compromettre leur adhésion au traitement. La définition consensuelle de la CIO date de 2016 et le développement de traitements ciblés, les antagonistes périphériques des récepteurs opioïdes (PAMORA) permettent désormais une gestion spécifique de la CIO sans nuire au soulagement de la douleur. Dans cette revue, nous explorerons la définition, la physiopathologie et les critères diagnostiques de la CIO ainsi que son épidémiologie. Nous verrons également les facteurs de risque et les examens cliniques et paracliniques nécessaires devant une CIO. L’impact de la CIO sur le traitement opioïde sera revu et les traitements existants, que ce soit les traitements non médicamenteux, ou les traitements médicamenteux de première et de seconde intention seront détaillés. Enfin, nous proposerons une synthèse des recommandations thérapeutiques actuelles proposées par les sociétés savantes.

INTRODUCTION:Despite the emergence of drugs to treat irritable bowel syndrome (IBS), improving abdominal pain can still be challenging. α2δ ligands, such as gabapentin and pregabalin, are sometimes used off-label to tackle this problem. However, evidence for efficacy is limited, and no large-scale studies have been published. AIM:To study the efficacy of the α2δ ligand PD-217,014 in IBS. METHODS:This multi-centre, double-blind, randomised, placebo-controlled, parallel group study randomised participants with Rome II-defined IBS to 150 or 300 mg b.d. of PD-217,014 or placebo b.d. for 4 weeks. The primary efficacy endpoint was responder, defined as having adequate relief of abdominal pain/discomfort for ≥ 50% of the active treatment period. Key secondary endpoints were change from baseline in abdominal pain, bloating, stool frequency/consistency, and global assessment of IBS symptoms. RESULTS:We randomised 330 participants [aged 19-73 years; 209 (65%) female] satisfying Rome II criteria, 322 (98%) were treated, and of whom 271 (84%) completed the study. In this study, 321 satisfied Rome IV criteria. Neither dose of PD-217,014 improved the percentage of participants reporting adequate relief of abdominal pain/discomfort compared with placebo, either using the Rome II-defined total cohort or Rome II and IV IBS bowel habit sub-types. There were similar observations for secondary endpoints, and no association between abdominal pain or anxiety levels at baseline with participant improvement. PD-217,014 was generally well tolerated. CONCLUSION:This first large, dose-ranging trial examining the efficacy of PD-217,014 showed no significant efficacy in participants with IBS or bowel habit sub-types, irrespective of their pain and anxiety levels.

Opioids are effective for acute and chronic pain management and are therefore an important treatment option for supportive care, especially in patients with cancer. They often induce digestive adverse effects, the most frequent being opioid-induced constipation (OIC), which is related to their action on m receptors in the gastro-intestinal tract. These receptors play a role in the regulation of the gut motility and secretions. OIC has frequently been overlooked, although it can impair patients' comfort and compromise their compliance with opioid treatment. The consensus definition of OIC was established in 2016, and targeted therapies, the peripherally acting m-m-opioid receptor antagonist (PAMORA) can yet specifically treat OIC without compromising pain relief. This review aims to explore the definition, pathophysiology, epidemiology, and diagnostic criteria of OIC. Risk factors and the necessary testing for the diagnostic work-up will be detailed. Finally, the impact of OIC on opioid treatment will be explained, and the treatment options, including non-pharmacological treatments, and pharmacological fi first-line and second-line therapies will be developed. A summary of the current therapeutic recommendations will be provided.

Abstract Background Vedolizumab is often used as the first-line advanced therapy for patients with moderate to severe ulcerative colitis (UC). There is currently no data reporting the efficacy and safety of second-line treatments after initial vedolizumab failure. The objective of our study was to compare the efficacy of anti-TNF, ustekinumab, and tofacitinib as 2nd line treatment of UC after vedolizumab exposure. Methods We conducted a retrospective multicenter study in 27 French and Belgian centers. All consecutive UC patients treated with vedolizumab between January 2019 and June 2023 as the first line and who received a 2nd line of anti-TNF, ustekinumab or tofacitinib were retrospectively included. The primary outcome was clinical remission at induction (week 14) defined by a clinical partial Mayo score ≤ 2 with no subscore > 1 without investigated treatment withdrawal. Clinical response was defined as a decrease in partial Mayo score of at least 30%. Results Among the 163 patients included, 94 (57.7%) were treated with anti-TNF (infliximab=71 (75.5%), adalimumab=21 (22.3%), and golimumab=2 (2.1%)), 56 (34.4%) with ustekinumab and 13 (7.9%) with tofacitinib. The median duration of the disease prior to second-line initiation was 9.5 months (IQR 16.0-146.0). The median duration of treatment with vedolizumab was 6 months (IQR 3.0-12.0). At week 14, 25/66 (37.9%) patients on infliximab, 7/23 (30.5%) on SQ anti-TNF (adalimumab and golimumab), 25/57 (43.9%) on ustekinumab and 7/13 (53.8%) treated with tofacitinib were in remission (p=0.49, Chi2 test). Response rates were 52.8%, 34.8%, 50.9%, and 53.8%, respectively, for the infliximab, antiTNF SC, ustekinumab, and tofacitinib groups. The survival without treatment discontinuation att 12 months was estimated at 51.6 (95% CI [39.6%-67.2%]) for infliximab, 45.7% (95% CI [28.5%-73.1%]) for SQ anti-TNF, 40.6% (95% CI [27.2%-60.6%]) for ustekinumab and 31.2% (95% CI [12.3%-79.2%]) for tofacitinib (p=0.95, log-rank test). Second-line treatment was discontinued in 41 patients (25.3%) for primary failure, 25 (15.4%) for secondary failure. Colectomy was required in 4 patients (2.5%) during follow-up. Infliximab was discontinued in 12 patients (12.8%) due to adverse reactions, including 6 allergic reactions. Among the 23 patients on SQ anti-TNF (adalimumab and golimumab), 2 required discontinuation (8.7%) due to adverse reactions. One side effect leading to discontinuation occurred with tofacitinib (7.7%) and none with ustekinumab. Conclusion After the failure of vedolizumab as a first-line biologic treatment for UC, the induction efficacy, persistence, and safety of the different second-line treatments seem similar. Current efforts to increase the sample size and strengthen the analysis is ongoing.

A 71-year-old patient was admitted after the accidental dislodgement of a computed tomography (CT)-guided percutaneous gastrostomy, placed 1 year prior. The initial procedure was uneventful and facilitated rapid weight gain. A percutaneous MIC-KEY tube (Avanos, Alpharetta, Georgia, USA) was rapidly placed along the previous route. As soon as nutrition was restarted, "on and off" profuse diarrhea occurred, ceasing as the nutrition was stopped and resuming immediately upon resumption. Opacification of the MIC-KEY tube revealed a fistulous tract between the transverse colon and the skin ([Video 1]). Conservative treatment was decided, involving the endoscopic closure of the residual colocutaneous fistula, achieved by placing an Ovesco clip (Ovesco Endoscopy, Tübingen, Germany) during a colonoscopy [1].

Abstract Background In patients admitted for acute severe ulcerative colitis (ASUC) responding to intravenous (IV) steroids, the most effective treatment is unknown. In thiopurine-naive patients, thiopurines are appropriate to maintain remission according to current guidelines while the benefit of early infliximab (IFX) therapy remains to be established. Methods In this multicentre, parallel group, open-label randomised controlled trial, thiopurine and biologics-naïve adults admitted for ASUC defined by a Lichtiger score >10 were included between 2016 and 2021 if they responded to IV steroids. They were randomly assigned to receive either combination therapy with IFX and azathioprine (AZA) with a quick steroid discontinuation (IFX+AZA arm), or AZA and standardized steroid tapering regimen (AZA arm). The primary endpoint was treatment failure at W52, defined as absence of steroid-free clinical remission (MCS≤2 with no individual subscore >1), absence of endoscopic response (Endoscopic subscore ≤1), use of a prohibited treatment, adverse event leading to interruption of allocated treatment, colectomy or death. A sample size of 73 patients per group was initially calculated. Due to challenges in recruiting patient, the steering committee decided to prematurely terminate the study blindly of any study results, after including 64 patients. Results 64 were randomised (32 males, age of 34.5 [26.3-50.3] years, Lichtiger score of 13.0 [12-14], CRP of 29.0 [12.8-96.8] mg/L and serum albumin of 31.2 [27.7-35.6] g/L at baseline): 32 were assigned to IFX+AZA arm and 32 to AZA arm. In ITT population, treatment failure at w52 was observed in 81.5% in the AZA arm versus 53.3% in the IFX+AZA arm (OR 3.85 [1.15-12.88], p=0.03). Components of the composite primary endpoint are given in table 1. In PP population, treatment failure at week 52 was observed in 81.5% (22/27) in the AZA arm versus 50.0% (13/26) in the IFX+AZA arm (OR 4.40 [1.28-15.18], p=0.02). In total 121 adverse events (AE) were reported in 40 patients including 23 serious AE in 18 patients (11 in the IFX + AZA arm and 7 in the AZA arm, p=0.24) and 8 leading to treatment interruption (5 in the IFX+AZA arm and 3 in the AZA arm, p=0.39). Serious AE included infectious AE in 6 cases (1 in the AZA arm and 5 in the IFX+AZA arm, p=0.20) and UC relapse in 9 (4 in the AZA arm and 5 in the IFX+AZA arm, p=0.60). No death was reported. Conclusion At w52, combination therapy with IFX + AZA and quick steroids discontinuation was more effective than AZA with standard steroids tapering regimen to prevent treatment failure in patients with ASUC responding to IV steroids. Combination therapy with IFX and AZA should be encouraged in ASUC patients responding to IV steroids (EudraCT 2014-005212-42; study funded by Pfizer).