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.

BACKGROUND & AIMS:Despite recent advances, refractory celiac disease (RCD) poses challenging questions. In type 2 RCD (RCD2), the lack of response to the gluten-free diet is attributed to an intestinal intraepithelial lymphoma-carrying driver JAK1 or STAT3 mutations. However, it remains unclear whether these can be safely targeted for therapy. In RCD1, pathogenic insights are still lacking. METHODS:Duodenal biopsy specimens and peripheral blood mononuclear cells from patients with RCD1, RCD2, active celiac disease (CeD), CeD in remission, and controls were analyzed. Lymphocyte populations were characterized using single-cell transcriptomic, genomic, and T cell receptor (TCR) repertoire profiling. Functional and exome sequencing analyses were performed on patient-derived RCD2 cell lines exposed to JAK inhibitors. RESULTS:We show that clonal malignant RCD2 lymphocytes exhibit interpatient similarities but substantial intratumoral heterogeneity, and provide in vitro evidence that JAK inhibitors can select drug-resistant tumor cells, arguing against their use as monotherapy. In RCD1, we identified clonal T-cell expansions harboring mutations that enhance the JAK-STAT pathway. The detection of both RCD2 and a CD4+ lymphoproliferation in a patient initially diagnosed with RCD1 further illustrates the diversity of lymphoproliferative outcomes in CeD. CONCLUSIONS:These findings suggest that RCD subtypes may share underlying mechanisms driven by clonal evolution and JAK-STAT dysregulation. They also highlight the potential limitations of JAK inhibitor monotherapy and the importance of molecularly informed therapeutic strategies.

INTRODUCTION:The management of inflammatory bowel disease (IBD) in patients with cystic fibrosis (CF) at risk of respiratory failure and severe lung infection is poorly described. The objective of this study was to describe the phenotype and evolution of IBD associated with CF, as well as the efficacy and tolerance of IBD treatments. MATERIALS AND METHODS:A national, multicentre, descriptive, retrospective study was conducted. The study included all adult patients with a confirmed diagnosis of CF and IBD identified across participating GETAID centres. Disease characteristics and outcomes were retrieved from patient charts. RESULTS:A total of 10 cases with IBD associated with CF were identified (six male; median age at diagnosis, 32 years; 10 with Crohn's disease (CD)). In CF, the DeltaF508 mutation was predominant; nine patients had lung involvement, and all had exocrine pancreatic involvement. Disease location and behaviour at diagnosis were similar to those observed in the general IBD population. During follow-up, four patients underwent surgery (40%), and nine patients were treated with immunosuppressants or biologics, resulting in clinical remission for 50% and 66%, respectively. Two patients with severe CF co-colonised with Pseudomonas Aeruginosa and Staphylococcus aureus experienced severe lung infection. CONCLUSION:Patients with CF are more likely to have CD than ulcerative colitis. In patients with advanced CF, the potential infectious risks associated with IBD therapies require individualised assessment.

INTRODUCTION:The concept of difficult-to-treat (D2T)/difficult-to-manage (DTM) disease was first defined in rheumatoid arthritis (RA). Recent definitions for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) combine non-response to treatment including targeted and biologic treatment, inflammatory disease activity, and patient symptoms. This concept could apply to other chronic inflammatory diseases such as psoriasis (PsO) and inflammatory bowel disease (IBD). A consensus definition of D2T IBD is available but is yet to be fully articulated in PsO. AREAS COVERED:This article aims to provide an expert overview of the shared elements and potential differences between the definitions and concepts of D2T/D2M in these diseases. EXPERT OPINION:D2T/D2M definitions should allow better evaluation of refractory diseases, accurate determination of disease severity, and effective treatment of the D2T areas or domains. Definitions should consider response to previous lines of treatment, control of inflammation, and global disease improvement, and consider the impact of D2T disease on patient status/quality of life. Proof-of-concept studies need to assess the current and future definitions of D2T/D2M populations in axSpA, PsA, PsO, and IBD, to accurately determine the prevalence of patients meeting each of those D2T criteria sets, and to identify risk factors, disease burden, and appropriate management strategies.

Vedolizumab (VDZ) has been available in France as a subcutaneous formulation for the treatment of inflammatory bowel diseases (IBD) since 2021. The aim of this study was to evaluate the persistence, efficacy and tolerance of subcutaneous VDZ (SC-VDZ) after switching from intravenous (IV) route. All patients with ulcerative colitis (UC) or Crohn’s disease (CD) in clinical remission for at least 3 months, who switched from IV-VDZ to SC-VDZ between February 2022 and April 2024, were included in a multicentric prospective French national cohort study. The date of the first SC-VDZ injection was the inclusion date. Clinical remission was defined as a partial Mayo score ≤ 2 in UC and a Harvey Bradshaw Index ≤ 4 in CD. Concomitant treatments (5-aminosalycilates, immunomodulators) were authorized at stable doses, whereas other advanced therapies were prohibited during the 12 months of the study. SC-VDZ was started at 108mg every other week. Primary endpoint was SC-VDZ persistence at week 54 (W54). Patients who had a disease-related surgery, repeated or prolonged (> 14 days) steroid courses and those who were lost to follow-up were considered non-persistent. A total of 337 patients were analyzed, after excluding 10 with active disease and one with an active infection at baseline: 246 (73%) UC patients (median disease duration: 7 years [interquartile range: 4-17]) and 91 (27%) CD patients (13 years [8-19]). UC patients had been on IV-VDZ for a median duration of 1.4 years [0.4-3.4], vs 3.1 years [1.4-6.0] in CD patients. In the whole cohort, 205 patients (62%) were on a standard IV-VDZ regimen (300 mg 8-weekly) prior to switch. At W54, SC-VDZ persistence was 84% [95% confidence interval: 80-88], without significant difference between UC and CD (p = 0.36). During the study period, 32 patients (10%) had a dose increase of SC-VDZ: 22 (9%) in UC and 10 (11%) in CD . Among them, 15 (48%) had been on a standard IV-VDZ regimen prior to switch, and six (19%) eventually stopped VDZ due to persistent loss-of-response despite dose increase. Three (9%) switched-back to IV-VDZ. In total, 16 (5%) patients switched-back to IV-VDZ (13 UC and 3 CD patients). Four months after the switch-back, 12/16 (75%) were still on IV-VDZ. Regarding tolerance, 183 patients (54%) reported at least one adverse event (AE), the most frequent being injection-site reaction (16%) and infections (13%). 25 AEs led to treatment discontinuation. 19 serious AEs were reported, among which only one acute diarrhoea potentially related to SC-VDZ without treatment discontinuation. Within this multicentric cohort of IBD patients, the persistence at one year from switch of SC-VDZ was 84%, with a favourable security profile. Pharmacokinetic data are pending. Conflict of interest: Dr. Hupé, Marianne: Abbvie, Takeda, Johnson & Johnson, Celltrion Healthcare, Lilly, Amgen, Pfizer Mathieu, Nicolas: Abbvie, Alphasigma, Celltrion Healthcare, Galapagos, Janssen, Lilly, Pfizer, Takeda, lecture fees from Abbvie, Alfasigma/Galapagos, Celltrion Healthcare, Janssen, Lilly, Mayoli-Spindler, Pfizer, Takeda, and has received research funding from, Celltrion Healthcare, Lessaffre, Lilly, Takeda Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Seksik, Philippe: Takeda, Janssen, Merck MSD, Biocodex, Ferring, Fresenius Kabi, Astellas, Amgen, Pfizer, Pilege and Abbvie Charkaoui, Maeva: TBC Gilletta de Saint Joseph, Cyrielle: Abbvie, AlfaSigma, Amgen, Celltrion, Ferring, Fresenius, Janssen, Lilly, Pfizer, Takeda and Tillots Serrero, Melanie: TBC Bouhnik, Yoram: TBC Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Roblin, Xavier: TBC Nancey, Stéphane: Abbvie, Takeda, Celltrion Healthcare, Pfizer, Galapagos, Johnson & Johnson, Lilly, Fresenius, Amgen, Medac, MSD Abitbol, Vered: Takeda, Amgen, Sandoz, Janssen, Celltrion, Pfizer, Alfasigma, Nordic Pharma, Abbvie, Lilly, Ferring Gornet, Jean-Marc: Abbvie, Amgen, Celltrion Healthcare, Fresenius-Kabi, Gilead, Janssen, Mylan, MSD, Takeda, Sanofi Céline, Montuclard: Abbvie Hebuterne, Xavier: Xavier Hébuterne reports clinical research funding from AbbVie, Abivax, Alphasigma, Arena Pharmaceuticals, Celgene, Eli Lilly, Enterome, Gilead, Janssen, InDex Pharmaceuticals, Pfizer, Roche, Salix, Sangamo, Takeda, Theravance, serving on advisory boards for AbbVie, Abivax, Arena Pharmaceuticals, Gilead, Janssen, Pfizer, Roche, Takeda, and participating in lectures and educational activities for AbbVie, Amgen, Baxter, Fresenius Kabi, Janssen, MSD, Mylan, Nutricia, Pfizer, Tillots, and Takeda. Paupard, Thierry: TBC Rouillon, Clea: Abbvie, Janssen, Biogen, Galapagos, Celltrion, Lilly Kaassis, Mehdi: No conflict of interest Andrau, Pierre: No conflict of interest Amil, Morgane: No conflict of interest Peyrin-Biroulet, Laurent: CONSULTING Abbvie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Banook, BMS, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, LifeMine, Medac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Par’ Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, Ventyx. LECTURE Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots Vicaut, Eric: No conflict of interest 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

INTRODUCTION:Women with endometriosis have a higher risk of developing inflammatory bowel diseases (IBDs). This study aimed to better understanding the impact of endometriosis on the course of IBD. METHODS:We conducted a retrospective cohort study in 18 French and Belgian IBD centers between June 2022 and March 2023. Any patient with both conditions was eligible for inclusion. They were randomly matched to 1 or 2 patients with IBD without endometriosis. The impact on IBD progression was assessed using a composite severity criterion including intestinal damage or need for bowel surgery. RESULTS:Overall, 207 patients with both conditions (149 Crohn's disease [CD]; 58 ulcerative colitis [UC]) were matched to 409 patients with IBD alone. The median follow-up duration for IBD was 10 years (5.75-17). No difference was observed between the 2 groups regarding CD location, disease phenotype, and anoperineal involvement. Proctitis were more frequent in patients with UC and endometriosis. Patients with IBD with endometriosis were significantly less exposed to immunosuppressants (UC P < 0.01; CD P < 0.001) and biologics (UC P < 0.01; CD P < 0.001). Patients with CD with endometriosis had a less severe disease course compared with patients without endometriosis (hazard ratio 0.68, 95% confidence interval 0.50-0.92, P = 0.011). Patients with UC with endometriosis had not a significant different disease course compared with patients without endometriosis (hazard ratio 1.73, 95% confidence interval 0.74-4.00, P = 0.20). These results were similar in the subgroup of patients with endometriosis treated surgically. DISCUSSION:Endometriosis does not negatively influence the course of IBD, patients with CD even have a less severe progression. Patients were significantly less exposed to immunosuppressants and biologics.

BACKGROUND & AIMS:Real-life data regarding inflammatory bowel disease (IBD) evolution after switch from intravenous infliximab (IV-IFX) to subcutaneous infliximab (SC-IFX) is necessary. The aim of this prospective multicenter cohort study was to describe the persistence, effectiveness and tolerance of SC-IFX after switch from IV-IFX. METHODS:IBD patients in steroid-free clinical remission for at least 6 months on IV-IFX were enrolled in a prospective national French cohort when they switched to SC-IFX. Patients were assessed at inclusion and at weeks 12, 24, and 48. The primary endpoint was the persistence of SC-IFX at week 48. Secondary endpoints comprised steroid-free clinical remission at week 48, IV-IFX switch-back rate, and evolution of infliximab levels during the study period. RESULTS:Among the 426 patients included (72.4% with Crohn's disease , 27.5% with ulcerative colitis; 45.1% female; median age 37 [interquartile range, 29-50] years; median disease duration of 12 years in Crohn's disease, 13 years in ulcerative colitis), 56% were on IV-IFX standard dosing (5 mg/kg 8-weekly) and 16% received combination therapy with an immunomodulator drug at baseline. At week 48, SC-IFX persistence was 95.4% (95% confidence interval, 93.3%-97.5%) and 86.9% of patients were on steroid-free clinical remission. Mean infliximab levels were 8.0 μg/mL at inclusion and 18.0 μg/mL at week 48 (P < .0001). Among the 19 (4.5%) patients who stopped SC-IFX, 6 (1.4%) switched back to IV-IFX. There were 222 adverse events reported in 42.4% of patients, and 12 led to treatment discontinuation, including 6 (1.4%) severe adverse events. CONCLUSIONS:In this large multicenter prospective cohort, persistence at 1 year of SC-IFX was more than 95% of IBD patients switched in remission from IV-IFX, confirming excellent effectiveness and tolerance of SC-IFX.

BACKGROUND AND AIMS:New techniques for endoscopic resection, including endoscopic submucosal dissection (ESD), have been developed to allow for en-bloc resection with very low recurrence rates and organ sparing in patients without inflammatory bowel disease (IBD). Data on ESD for the management of colorectal dysplasia in IBD patients are scarce. We aimed to evaluate the efficacy and safety of ESD for the treatment of IBD. METHODS:We conducted a retrospective multicenter cohort study that evaluated consecutive ESD procedures in IBD patients with visible dysplasia from 20 French centers with ESD experience. Between June 2008 and March 2022, all IBD patients included in the local ESD databases and who underwent ESD for visible dysplasia proven on biopsy were included. All patients were included from the date ESD was performed, and endoscopic follow-up and surgical data were collected. RESULTS:Among the 88 lesions resected in 82 patients (19 patients with Crohn's disease), 82% and 80% of patients had R0 and curative resection, respectively. Ten (12%) patients required surgery: 1 for complication, 3 for endoscopic failure, and 6 for noncurative resection. After a median follow-up of 20 (IQR 10.5-45) months, 4 patients experienced local recurrence, and 14 (17%) underwent surgery. Two patients died from cardiovascular issues during the follow-up. Factors associated with local recurrence were R1 resection, associated primary sclerosing cholangitis, a personal history of colorectal cancer, and active lesions at the ESD site. CONCLUSIONS:Endoscopic submucosal dissection is feasible for IBD patients with visible colorectal dysplasia and has an acceptable safety profile. These findings should be evaluated further in control trials.

New techniques for endoscopic resection, including endoscopic submucosal dissection (ESD), have been developed to allow for en-bloc resection with very low recurrence rates and organ sparing in patients without inflammatory bowel disease (IBD). Data on ESD for the management of colorectal dysplasia in IBD patients are scarce. We aimed to evaluate the efficacy and safety of ESD for the treatment of IBD. We conducted a retrospective multicenter cohort study that evaluated consecutive ESD procedures in IBD patients with visible dysplasia from 20 French centers with ESD experience. Between June 2008 and March 2022, all IBD patients included in the local ESD databases and who underwent ESD for visible dysplasia proven on biopsy were included. All patients were included from the date ESD was performed, and endoscopic follow-up and surgical data were collected. Among the 88 lesions resected in 82 patients (19 patients with Crohn's disease), 82% and 80% of patients had R0 and curative resection, respectively. Ten (12%) patients required surgery: 1 for complication, 3 for endoscopic failure, and 6 for noncurative resection. After a median follow-up of 20 (IQR 10.5-45) months, 4 patients experienced local recurrence, and 14 (17%) underwent surgery. Two patients died from cardiovascular issues during the follow-up. Factors associated with local recurrence were R1 resection, associated primary sclerosing cholangitis, a personal history of colorectal cancer, and active lesions at the ESD site. Endoscopic submucosal dissection is feasible for IBD patients with visible colorectal dysplasia and has an acceptable safety profile. These findings should be evaluated further in control trials.

INTRODUCTION:Phosphatidylinositol 3-kinase-δ (PI3Kδ) inhibitors have been approved for treatment of patients with chronic lymphocytic leukemia and non-Hodgkin's lymphomas and may lead to enterocolitis. PATIENTS AND METHODS:This is a multicenter, retrospective cohort study. Consecutive patients treated with PI3Kδ inhibitors who developed severe enterocolitis. RESULTS:Between 2014 and 2023, 31 out of 133 (23 %) patients exposed to PI3Kδ inhibitors had severe enterocolitis. Among them, 71 % required hospitalization, 64 % experienced weight loss and 39 % of patients had acute kidney injury. Endoscopic lesions were mild in 15/19 patients while four patients had shallow ulcers. Histopathological examination of colonic biopsies was abnormal in all cases. The most common lesions were neutrophilic cryptitis, crypt abscesses, crypt epithelial cell apoptosis and crypt architectural abnormalities. PI3Kδ inhibitors were discontinued in 24 cases (77 %). At day 30, clinical remission was achieved in 0/7 patients who continued PI3Kδ-inhibitor and in all patients who discontinued PI3Kδ-inhibitor (p < 0.001) with no benefit of adding prednisone or budesonide to treatment discontinuation. Relapse of diarrhea occurred in four out of seven (57 %) patients who resumed half-dosed PI3Kδ inhibitor. CONCLUSION:Severe enterocolitis associated with PI3Kδ inhibitors is frequent and respond to drug withholding. Steroids do not seem to provide additional benefits. Rechallenge is often accompanied by a relapse.

OBJECTIVES:To describe the characteristics and outcome of patients with the association of large vessel vasculitis (LVV, Takayasu arteritis [TA] or GCA) and IBD. METHODS:An observational, multicentre, retrospective case-control study. Cases were LVV-IBD patients from European countries, whereas controls had isolated LVV (iLVV). RESULTS:A total of 39 TA-IBD and 12 GCA-IBD cases were enrolled, compared with 52 isolated GCA (iGCA) and 93 isolated TA (iTA) controls. LVV occurred after IBD in 56% in TA-IBD and 75% in GCA-IBD, with a median interval of 1 year (interquartile range [IQR] 1-7) in TA-IBD and 8.6 years (IQR 1-17.7) in GCA-IBD. Crohn's disease was more common in TA-IBD (67%), whereas ulcerative colitis was more common in GCA-IBD (58%). Compared with iTA, TA-IBD were significantly younger at diagnosis of TA (median age 27 vs 37 years, P < 0.001) and had more upper limb claudication (36% vs 12%, P = 0.006). GCA-IBD patients had more frequent arterial thickening or stenosis than controls (75% vs 30%, respectively, P = 0.044) and tended to more frequently involve gastrointestinal arteries (20% vs 0%, respectively, P = 0.06). LVV occurred in IBD patients despite treatment with glucocorticoids (36%), azathioprine (25%) or TNF-alpha blockers (29%). The presence of the IBD was not associated with a higher LVV relapse rate in multivariate analysis (adjusted hazard ratio [aHR] 0.62 [0.13-2.83] for GCA and aHR 0.92 [0.44-1.89] for TA). CONCLUSION:This study identifies specific clinical and imaging characteristics of LVV-IBD patients, in particular a more severe vascular presentation of GCA-IBD patients compared with iGCA patients.

Background: The effectiveness of advanced therapies beyond second-line therapies has been poorly described in patients with ulcerative colitis (UC). Aim: To describe the outcomes of third-line advanced therapy in patients with UC in a real-world setting. Methods: We conducted a multicentre retrospective study in patients with UC who received third-line advanced therapy after the failure of a first-line anti-TNF agent and second-line vedolizumab. The primary endpoints were steroid-free clinical remission at weeks 14 and 54. Results: We analysed 237 therapeutic sequences in 150 patients (55 with an anti-TNF agent, 80 with tofacitinib, and 102 with ustekinumab), accounting for 245.3 patient-years. Steroid-free clinical remission at week 14 was achieved in 14 (25.5 %) patients treated with an anti-TNF agent, 40 (50.0 %) with tofacitinib, and 54 (52.9 %) with ustekinumab (RR = 1.96 [1.19-3.25] for tofacitinib and RR = 2.08 [1.28-3.39] for ustekinumab, compared with an anti-TNF agent, respectively). Steroid-free clinical remission at week 54 was achieved in 16 (29.1 %) patients in the anti-TNF group, 37 (46.2 %) in the tofacitinib group and 56 (55.4 %) in the ustekinumab group (RR = 3.07 [0.98-9.60] for tofacitinib and RR = 3.09 [1.01-9.43] for ustekinumab, compared with anti-TNF, respectively). In total, 13.7 % of the patients underwent colectomy. Adverse events occurred in 94 (39.7 %) patients and were less frequent with ustekinumab. Conclusion: In this retrospective study, third-line advanced therapies resulted in a high rate of steroid-free clinical remission at weeks 14 and 54, especially in patients treated with ustekinumab and tofacitinib.

Abstract Background Prospective data after switch from intravenous infliximab (IV-IFX) to subcutaneous (SC-IFX) in Inflammatory Bowel Disease (IBD) is needed. The aim of this prospective multicenter cohort was to describe SC-IFX persistence, efficacy and tolerance after switch from IV-IFX. Methods IBD patients in steroid-free clinical remission (defined by a Harvey Bradshaw index (HBI) ≤ 4 for Crohn’s disease (CD), and partial Mayo Score (PMS) ≤ 2 with no subscore >1 for ulcerative colitis UC)) for at least 6 months on IV-IFX, were enrolled in this prospective cohort if they switched to SC-IFX. Clinical (HBI, PMS), biological (CRP, fecal calprotectin (FC)) and pharmacokinetic evaluations were performed at 3, 6, 12 and 24 months from switch. In case of clinical or biological relapse, as per physicians’ judgement, SC-IFX dose could be increased, or drug changed. Primary endpoint was SC-IFX persistence at week 48 (W48). Secondary endpoints comprised steroid-free clinical remission at W48, proportion of patients who switched back to IV-IFX, HBI and PMS changes and FC, CRP and infliximab serum level changes. Statistical comparisons were performed using Fisher’s exact test. Survival without treatment discontinuation was analysed using a Kaplan-Meyer curve. Results 426 patients were included (72.4% CD, 45.1% female, median age 37 years), with a median time from diagnosis of 143 months in CD, 154 months in UC. At baseline, 74% were on IV-IFX standard dose (5mg/kg every 8-week) and 68 (16%) received combination therapy with an immunosuppressant. Among patients with complete data until W48, SC-IFX persistence was 95.3% (CI, 93.2-97.5). 319/367 (89.9%) were on steroid-free clinical remission. From baseline to W48, median HBI and PMS scores were 0, CRP did not change significantly, median FC rate decreased significantly from 52µg/g to 36 µg/g (p=0.015). Mean Infliximab trough level at inclusion was 7.97µg/mL, while it reached 17.96µg/mL at W48 (p<0.0001). 23 (5.4%) patients had an increase of SC-IFX dose and 22 (5.2%) stopped SC-IFX, of which 6 patients switched back to IV-IFX. SC-IFX persistence was significantly higher among patients treated with SC-IFX monotherapy (98.8%) as compared to those on combination therapy (90.0%) (HR=0.14 [0.04-0.53]). Adverse events were reported in 181/426 patients (42.4%), 12 led to treatment discontinuation. Nine severe adverse events (2%) were reported. Three patients (0.7%) had IBD-related surgery and 8 (1.9%) IBD-related hospitalization. Conclusion In this large multicenter prospective cohort of IBD patients in remission, one-year persistence of SC-IFX after switch from IV-IFX was 95.3%, supporting excellent efficacy and tolerance of SC-IFX.

Background: Switching from a reference product (RP) to a biosimilar (BS) aims to generate savings. Patient adherence after a switch is linked to overall experience that can be impacted by patient or treatment characteristics. Objectives: This study aimed to analyse patient-experience and satisfaction after the switch from an adalimumab (ADA) RP or BS to CT-P17[1] (ADA BS high concentration (HC), citrate-free). Methods: YU-MATTER (NCT05427942), a multicentric prospective observational study included patients with chronic inflammatory rheumatic disease (CIR) or inflammatory bowel disease (IBD) treated with ADA: either the RP (HC: 100mg/ml) or a BS with low concentration (LC: 50 mg/ml). Patients were switched to CT-P17 and followed-up for 3 months (M). Clinical characteristics were collected at M0, including patient-experience via 5 self-questionnaires developed in collaboration with patient associations to explore satisfaction regarding the injection (Likert 7), discomfort (pain [NRS 0-10], redness [Likert 4], itching [NRS 0-10], and haematoma [Likert 3]). Satisfaction and overall injection tolerance (pain < 4 AND absence of redness AND itching < 4 AND absence of haematoma) were assessed between M0 (just before switch) and M3 (3 months after switch). Factors associated with satisfaction improvement (Likert) were explored through multivariable logistic regression. Results: Of the 232 patients analysed, the rheumatology population counted 65 patients with CIR (RA=17, AS=35, nr-axSpA=7, PsA=6,). mean age was 54±9 years; median disease duration was 9 years ([Q1; Q3]: [5; 18]) and 49.2% were men. Over the analysed population, 119 (51.2 %) patients were switched from a BS (45 with citrate) and 113 (48.7%) from the RP. At 3 months, 175 patients (75.4%) were satisfied with the injection and 145 (62.5%) had a stable or improved satisfaction versus the previous ADA. Among patients receiving a BS, the presence of citrate was significantly associated with an improvement of satisfaction after switching to CT-P17 (58.3% vs. 30.0%, p=0.006). Overall injection tolerance significantly improved after switching from 28.9 % at M0 to 57.7 % at M3 (p<0.0001). A significant decrease of pain related injection was observed after the first injection of CT-P17 (median -2 [-4;-1]) for patients switched from a BS and remained stable for patients switched from the RP (median 0 [-1;1]). In multivariable analysis, the switch from a LC ADA was an independent factor of satisfaction improvement (vs from the RP, odds ratio=3.03; p=0.003; Table 1). Conclusion: The global experience of switching to CT-P17 was positive with an overall improvement in injection tolerance. Injection volume was an independent factor associated with a successful experience. REFERENCES: [1] Furst DE, and al. Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis. Rheumatology (Oxford). 2022.[2] Horne R, and al. The Beliefs about Medicines Questionnaire: The Development and Evaluation of a New Method for Assessing the Cognitive Representation of Medication. Psychology & Health 1999. Acknowledgements: We thank all patients for their active participation in the study by answering questionnaires, patient associations (AFA, ANDAR, AFS) for their contribution to the study design and e-Health Services Sanoïa for the follow-up during the study and their input to results interpretation. Disclosure of Interests: Hubert Marotte AbbVie, Amgen, Bristol Myers Squibb, Celltrion HealthCare, Galapagos, Lilly France, MerckSharp & Dohme, Novartis, Nordic Pharma, Pfizer, and Sanofi Aventis, AbbVie, Amgen, Bristol Myers Squibb, Celltrion HealthCare, Galapagos, Lilly France, MerckSharp & Dohme, Novartis, Nordic Pharma, Pfizer, and Sanofi Aventis, Bristol Myers Squibb, Celltrion HealthCare, Galapagos, Lilly France, Novartis, Nordic Pharma, Pfizer, andSanofi Aventis, Laure Gossec AbbVie, Amgen, BMS, Celltrion Healthcare, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, AbbVie, Amgen, BMS, Celltrion Healthcare, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Lilly, Pfizer, Sandoz, UCB, AbbVie, Amgen, BMS, Celltrion Healthcare, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Lilly, Pfizer, Sandoz, UCB, Vered Abitbol Pfizer, Takeda, Amgen, Mylan Viatris, Sandoz, Janssen, Fresenius, Gilead, Tillotts, Celltrion, Pfizer, Takeda, Amgen, Mylan Viatris, Sandoz, Janssen, Fresenius, Gilead, Tillotts, Celltrion, Eric Senbel Lilly, Nordic, Roche, Chugai, Novartis, Sandoz, Biogen, Fresenius Kabi, Abbvie, Amgen, Biogen, Celltrion HealthcareNordic, Roche, Chugai, AbbVie, Amgen, Pfizer, Sanofi, MSD, Biogen, Janssen, Fresenius KabiNordic, Roche, Chugai, Fresenius Kabi, Celltrion HealthcareGuillaume Bonnaud Abbvie, Amgen, Biogen, Celltrion, Cvasthera, Ferring, Fresenius, Galapagos, Gilead, Mayoli Spindler, MSD, Janssen, Pfizer, Roche, Takeda, Tillots, Sandoz, ViatrisXavier Roblin Celltrion, MSD, Pfizer, Abbvie, Amgen, Biogen, Takeda, Janssen, BMS, Ferring, Tillots, ViforYoram Bouhnik Abbvie, Amgen, Biogaran, Biogen, Boehringer Ingelheim, Celltrion Healthcare, Ferring, Fresenius Kabi, Galapagos, Gilead, Hospira, Iterative Scopes, Janssen, Lilly, Mayoli Spindler, Merck, MSD, Norgine, Pfizer, Roche, Sandoz, Sanofi, Shire, Takeda, Tillotts, UCB, ViatrisStephane Nancey Takeda, Pfizer, MSD, Abbvie, Janssen, Tillots, HAC Pharma, Novartis, Amgen, Sanofi, Hospira, Biogen, Roche, Sandoz, Celltrion, Boerhinger Ingelheim, Nicolas Mathieu Atawao Healthcare, Celltrion, CTMA, Gilead, Janssen, Abbvie, Amgen, Biogen, Ferring, Gilead, MSD, Janssen, Pfizer, Sandoz, TakedaCelltrion, Mylan, Sandoz, Abbvie, Amgen, Janssen, Pfizer, TakedaJérôme Filippi Abbvie, Amgen, Biogen, Celltrion, Galapagos, HAC pharma, Janssen, MSD, Pfizer, Sandoz, Takeda, TillottsLucine Vuitton: None declared, Stéphane Nahon Celltrion Healthcare, Abbvie, Fresenius, Amgen, Celltrion Healthcare, Abbvie, Fresenius, Amgen, Azeddine Dellal Celltrion Healthcare France, Fresenius Kabi, Alice DENIS Celltrion Healthcare France, Caroline HABAUZIT Celltrion Healthcare France, Salim Benkhalifa Celltrion Healthcare France, Guillaume BOUGUEN AbbVie, Takeda, MSD, Janssen, Celltrion, AbbVie, Takeda, Mylan, Pfizer, Sandoz, Amgen, Ferring, Janssen, Celltrion, AbbVie, Takeda, Fresenius, Janssen, Vifor, Sandoz.Table 1Multivariable analysis of factors associated in improvement of satisfaction at 3 months with CT-P17 for 189 patients.OR [95% CI] (p-value)Adalimumab biosimilar LC vs. Adalimumab RP HC3.03 [1.46- 6.29] (0.003)CT-P17 pen vs CT-P17 syringe4.97 [1.38- 17.87] (0.014)Pain at injection site at M0 (for 1 point)1.17 [1.01- 1.35] (0.032)

Background: Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown. Objectives: This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator. Design: In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d’Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale. Methods: The differences in responses were performed using a one-way analysis of variance followed by Tukey’s honest significant difference test. Results: The most commonly used drugs at inclusion were Humira ® (436/941, 46.3%), Amgevita ® (177/941, 18.8%) and Hulio ® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) ( p < 0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma ® (9.0 (1.4)), Humira (8.9 (1.3)) and Hulio (8.9 (1.7)) ( p < 0.05). A total of 299 patients (31.8%) described injection site reactions. In all, 223 patients (23.7%) reported being previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects. Conclusion: In this real-world setting, patients with IBD had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.

BACKGROUND & AIMS:Breast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD). The aim of our study was to evaluate incident cancer rate (recurrence or new-onset cancer) in a cohort of patients with IBD with a history of breast cancer according to the subsequent IBD treatment provided. METHODS:A multicenter retrospective study included consecutive patients with IBD with prior breast cancer. The inclusion date corresponded to the diagnosis of index malignancy. Follow-up lasted from cancer diagnosis until the occurrence of incident cancer. RESULTS:Among 207 patients included (median disease duration, 13 years [interquartile range, 6-21]), first-line treatment (median interval of 28 months [interquartile range, 7-64]) was a conventional immunosuppressant in 19.3% of patients, anti-tumor necrosis factor in 19.8%, vedolizumab in 7.2%, and ustekinumab in 1.9%. After a median follow-up of 71 months (interquartile range, 34-148), 42 (20%) incident cancers were observed (34 breast cancer recurrences). Adjusted incidence rates per 1000 person-years were 10.2 (95% confidence interval, 6.0-16.4) for the untreated arm and 28.9 (95% confidence interval, 11.6-59.6) for exposed patients (P = .0519). There was no significant difference between treated patients and control subjects regarding incident cancer-free survival rates (P = .4796). In multivariable analysis, factors associated with incident cancer were stage T4d (P = .036), triple negative tumor (P = .016), and follow-up of less than 71 months (P = .005). CONCLUSIONS:We did not find a statistically significant increase in incident breast cancer related to IBD treatment beyond the already known poor prognostic factors of breast cancer.

BACKGROUND & AIMS:The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with Crohn's Disease (CD). METHODS:From May 2021 to August 2023, all consecutive patients with CD treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index [HBI] <5) at 52 weeks. RESULTS:Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics, and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 months (interquartile range, 10.0-18.1 months). The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174; 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174; 20.9%) were hospitalized, and 22 (22/174; 12.6%) required intestinal resection. Fifty-one patients (29%) had an adverse event, including 26 (15%) serious adverse events (CD flare, n = 17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION:This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. One-half of the patients achieved steroid-free clinical remission after 1 year, and the safety profile was consistent with the literature.

Biosimilars are cost-effective alternatives to reference products for patients with inflammatory bowel diseases (IBD) and chronic inflammatory rheumatic diseases (CIRD), but patient beliefs can affect adherence to the transition. This study aimed to explore patient experience and satisfaction after switching to CT-P17, a high-concentration (100 mg/mL), citrate-free adalimumab biosimilar. This observational, multicenter, prospective French study included adult patients with IBD or CIRD who switched to CT-P17 from reference adalimumab (R-ADA; 100 mg/mL) or a low-concentration adalimumab biosimilar (ADA-BioS; 50 mg/mL). Patients completed online questionnaires to assess treatment perceptions, satisfaction, and tolerance at study inclusion (under previous treatment) and over 3 months of CT-P17 treatment. The primary criterion was overall patient satisfaction, which was assessed with the question, “What is your global satisfaction with the CT-P17 injection?”, using a 7-point Likert scale. Multivariate logistic regression analysis was performed to identify factors associated with increased treatment satisfaction after switching to CT-P17. The total analysis population included 232 patients (IBD 72.0

Background The advent of anti-tumor necrosis factor alpha (anti-TNF alpha) has revolutionized the treatment of inflammatory bowel disease (IBD). However, susceptibility to active tuberculosis (TB) is associated with this therapy and requires its discontinuation. The risk of immune reconstitution inflammatory syndrome (IRIS) in this population is poorly understood, as is the safety of resuming anti-TNF alpha.Methods This French retrospective study (2010-2022) included all TB cases in patients with IBD who were treated with anti-TNF alpha in 6 participating centers. A systematic literature review was performed on TB-IRIS and anti-TNF alpha exposure.Results Thirty-six patients were included (median age, 35 years; IQR, 27-48). TB was disseminated in 86% and miliary in 53%. IRIS occurred in 47% after a median 45 days (IQR, 18-80). Most patients with TB-IRIS (93%) had disseminated TB. Miliary TB was associated with IRIS risk in univariate analysis (odds ratio, 7.33; 95% CI, 1.60-42.82; P = .015). Anti-TB treatment was longer in this population (median [IQR], 9 [9-12] vs 6 [6-9] months; P = .049). Anti-TNF alpha was resumed in 66% after a median 4 months (IQR, 3-10) for IBD activity (76%) or IRIS treatment (24%), with only 1 case of TB relapse. Fifty-two cases of TB-IRIS in patients treated with anti-TNF alpha were reported in the literature, complicating disseminating TB (85%) after a median 42 days (IQR, 21-90), with 70% requiring anti-inflammatory treatment. Forty cases of TB-IRIS or paradoxical reaction treated with anti-TNF alpha were also reported. IRIS was neurologic in 64%. Outcome was mostly favorable (93% recovery).Conclusions TB with anti-TNF alpha treatment is often complicated by IRIS of varying severity. Restarting anti-TNF alpha is a safe and effective strategy.