Introduction

PRA023 is a humanized monoclonal antibody against tumor necrosis factor–like cytokine 1A (TL1A), a key pro-inflammatory cytokine and pro-fibrosis regulator, in development for inflammatory bowel diseases. In a phase 2 double-blind, placebo-controlled study (ARTEMIS-UC) assessing the efficacy and safety of PRA023 induction treatment in adults with moderately to severely active ulcerative colitis (UC), a significantly greater proportion of patients who received PRA023 achieved the primary endpoint of clinical remission after 12 weeks. This post hoc analysis assessed the impact of PRA023 on health-related quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ-32).

Aims & Methods

Adults with a modified Mayo score of 4 to 9, centrally read endoscopy subscore of ≥2, rectal bleeding subscore of ≥1, and history of insufficient response, loss of response, and/or intolerance to conventional and/or advanced therapies (≤4 advanced agents from ≤3 classes allowed) were stratified by prior biologic exposure and genetic-based diagnostic status and randomized 1:1 to placebo or intravenous PRA023 (1000 mg on day 1, and 500 mg at weeks 2, 6, and 10). IBDQ outcomes measures include: IBDQ response (score of ≥16-point from baseline), IBDQ remission (total score ≥170), and mean change from baseline in total and domain scores after 12 weeks of induction therapy. Score changes from baseline were compared among treatment groups, and the impact of prior advanced therapy exposure on IBDQ remission was assessed. Higher scores represent better quality of life.

Results

Of the 135 patients in the study, 60/67 (89.6%) in the placebo arm and 68/68 (100%) in the PRA023 arm completed the 12-week induction period. Baseline characteristics were similar between the treatment groups. Significantly greater proportions of patients in the PRA023 group achieved IBDQ response (82.4% PRA023 vs 49.3% placebo, ∆33.1%, p<0.0001) and IBDQ remission (51.5% PRA023 vs 19.4% placebo, ∆32.1%, p=0.0001) at week 12. Prior advanced therapy use did not affect the placebo-adjusted proportion of patients experiencing IBDQ remission in those who received PRA023 (Δ34.4% vs Δ30.0%, respectively, for prior and no prior advanced therapy). The total IBDQ score and all IBDQ domain subscores (bowel symptoms, systemic symptoms, emotional function, and social function) were significantly improved after 12 weeks of PRA023 induction treatment compared to placebo (Table 1).

Table 1. Inflammatory Bowel Disease Questionnaire (IBDQ) Outcomes with PRA023 Induction Therapy

Conclusion

PRA023 significantly improved quality-of-life measures in patients with moderately to severely active UC, regardless of prior advanced therapy use. The greatest benefits were reported in the bowel symptoms and emotional function domains.

Disclosure

LPB has served as a consultant for or has received fees from AbbVie, Allergan, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Eli Lilly and Company, Enterome, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, Hikma, Index Pharmaceuticals, Inotrem, Janssen, MSD, Mylan, Oppilan Pharma, OSE Immunotherapeutics, Nestlé, Norgine, Roche, Pandion Therapeutics, Pfizer, Pharmacosmos, Samsung Bioepis, Sandoz, sterna biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tillotts Pharma, and Vifor; has received grants from AbbVie, Fresenius Kabi, MSD, and Takeda; and has stock options from CTMA.
BES has served as a consultant for or received speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion Healthcare, ClostraBio, Connect Biopharma, Cytoki Pharma, Eli Lilly and Company, Entera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead, Genentech, GSK, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kallyope, Merck, MiroBio, Morphic Therapeutic, MRM Health, OSE Immunotherapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, and Viela Bio and has received stock options from Ventyx Biosciences.
SD has received consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Eli Lilly and Company, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, and Vifor and lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
DTR has served as a consultant for AbbVie, AltruBio, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Chronicles, Corp/Syneos, ClostraBio, Connect Biopharma, Eco R1, Eli Lilly and Company, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido, Pfizer, Prometheus Biosciences, Reistone Biopharma, Seres Therapeutics, Takeda, Target RWE, and Trellus Health and has received grant support from Takeda, Helmsley Charitable Trust, and the Gastro-Intestinal Research Foundation.
DDN, QD, AM, and BD are employees and shareholders of Prometheus Biosciences.
CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma, BIOJAMP, Bristol Myers Squibb, Celltrion Healthcare, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Prometheus Biosciences, Roche, and Sanofi; speaker's fees from AbbVie, Amgen, AVIR Pharma, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer; royalties from Springer Publishing; and research support from Ferring and Pfizer.
TER has been a speaker for Takeda Pharmaceuticals, Janssen, Pfizer, Bristol Myers Squibb, and Abbvie; has served on advisory boards for AbbVie, Ardelyx, Arena, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Eli Lilly and Company, Ferring, Genentech/Roche, Gilead, Intercept, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Sanofi, and Takeda; and has been a shareholder for Iterative Scopes.
RP has been a consultant for Abbott, AbbVie, Abivax, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly and Company, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB; has received speakers fees from AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda; and has served on advisory boards for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda, and Ventyx.

Introduction

Active inflammatory bowel disease in pregnancy is associated with an increased risk of adverse maternal and neonatal outcomes. Understanding patterns of disease activity may inform strategies for improving outcomes.

Aims & Methods

A retrospective cohort study was conducted of pregnancies managed through an IBD–antenatal clinic between August 2020 and January 2025. Patients were stratified into 2 groups based on disease activity during pregnancy. Active disease was defined using the Physician Global Assessment, symptoms, and biomarkers (CRP and/or FCP). Disease flare was defined by an increase in symptoms and/or biomarkers from their baseline. Disease activity was assessed pre-conception (within 6 months before pregnancy) during pregnancy and post-partum (up to 6 months post birth).

Results

Of 209 pregnancies (Table 1), 76.3% (n=158) were in remission and 23.7% (n=49) had active disease pre-conception. Among those with active disease, 81.6% (n=40) remained active into pregnancy, while 18.4% (n=9) achieved remission. Of those in remission at pre-conception, 73.4% (n=116) stayed in remission during pregnancy, and 24.7% (n=39) flared. 2 patients with no pre-conception data were active in pregnancy.
Of 125 patients in remission during pregnancy, 73.6% (n=92) stayed in remission post-partum and 12.0% (n=15) flared. Among 81 patients with active disease in pregnancy, 39.5% (n=32) remained active, and 53.0% (n=43) achieved remission post-partum.
Patients in remission through pregnancy had a higher mean BMI (24.5 vs 23.0 kg/m², p=0.027), were more likely to be of white ethnicity compared to minority ethnic groups (61.0% vs 38.4% p=0.0026), have a diagnosis of Crohn’s disease (58.6% vs 37.0%, p=0.0088), and be nulliparous (51.2% vs 35.0%, p=0.0414).
At conception, approximately 30% of patients in both groups were not receiving any treatment. During pregnancy, this proportion fell to 8.6% in the active group, reflecting therapy escalation. Use of biologics increased from 22.2% to 38.2% in the active group and remained stable at 36.0% in the remission group. Corticosteroid use was exclusive to the active disease cohort (6.2% at conception; 23.5% during pregnancy).
Active disease in pregnancy was associated with higher rates of adverse outcomes: gestational diabetes (12.3% vs 8.0%, p=0.001), fetal growth restriction (4.9% vs 0%, p=0.044), and low birth weight (<2500g: 14.6% vs 2.4%, p=0.015). While rates of small for gestational age infants were higher in the active group (9.9% vs 4.0%), this was not statistically significant.
Emergency c-sections were more common in the active group (29.9% vs 15.0%, p=0.03), while elective c-sections were more frequent in the remission group (27.5% vs 13.4%, p = 0.03). Women in remission more often had an intact perineum (63.6% vs 54.7%), while episiotomy was more frequent in those with active disease (18.8% vs 11.7%); both did not reach statistical significance.

Conclusion

This study underscores the impact of active IBD on maternal and neonatal outcomes.
Nearly 1 in 4 women in remission at preconception flared during pregnancy. This highlights the need for effective pre-conception counselling, access to disease monitoring tools, multidisciplinary management and timely treatment optimisation to sustain remission during pregnancy.

Disclosure

No disclosures

Introduction

Difficult-to-treat Crohn’s disease (CD), as defined by the International Organization for the Study of IBD (IOIBD), encompasses patients with persistent disease activity despite advanced therapies, complex phenotypes (e.g., penetrating complications), or post-surgical recurrence. Upadacitinib, a selective JAK1 inhibitor, has demonstrated efficacy in Western populations, yet data in Asian cohorts remain sparse. This study evaluates the effectiveness and safety of standardized induction regimen of upadacitinib (45mg qd) in Asian patients meeting IOIBD criteria for difficult-to-treat CD.

Aims & Methods

To assess the efficacy and safety of upadacitinib in Asian patients with difficult-to-treat CD, providing evidence for clinical decision-making, a retrospective, multicenter study was conducted from 8 Chinese tertiary centers (January 2023–January 2025) on difficult-to-treat Crohn’s disease patients who met IOIBD criteria. All patients received upadacitinib 45mg qd for 12 weeks. Clinical outcomes were assessed using the Crohn's Disease Activity Index (CDAI), with the primary outcome being clinical remission (CDAI <150) and the secondary outcome being clinical response (CDAI reduction ≥70) at week 12. Adverse events (AEs) were systematically recorded.

Results

We finally collected 151 patients who met IOIBD criteria(Table1). Among them, 147 patients presented failure of ≥2 biologics with distinct mechanisms, 3 patients had complex perianal disease and 1 patient had postoperative recurrence. The mean disease duration of these patients was 7.6 years (SD 4.5 years). At week 12, 71 patients (47.0%) achieved clinical remission, 66 patients (43.7%) showed clinical response, and 14 patients (9.3%) were non-responders. Adverse events occurred in 40 patients (26.5%): acne (n=13), anemia (n=13), leukopenia (n=3), fever (n=4), urinary tract infection (n=2), herpes zoster (n=2), folliculitis (n=1), amenorrhea (n=1), elevated creatine phosphokinase (n=1), and mediastinal tuberculosis (n=1). Most AEs were mild and resolved with oral medications.

Table1. Baseline Characteristics of Patients with Difficult-to-Treat CD Treated with UPA

Conclusion

This is the largest Asian cohort study of upadacitinib for difficult-to-treat CD. The drug demonstrated robust efficacy and a favorable safety profile. Notably, tuberculosis reactivation was rare. Standard dosing showed comparable effectiveness and tolerability to European data, underscoring upadacitinib as a strong therapeutic option in Asian populations.

References

1. Parigi TL, D'Amico F, Abreu MT, et al. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023;8(9):853-859. doi:10.1016/S2468-1253(23)00154-1
2. Parigi TL, Massimino L, Carini A, et al. Prevalence, Characteristics, Management, and Outcomes of Difficult-to-Treat Inflammatory Bowel Disease. J Crohns Colitis. 2025;19(3):jjae145. doi:10.1093/ecco-jcc/jjae145
3. Bezzio C, Franchellucci G, Savarino EV, et al. Upadacitinib in Patients With Difficult-to-Treat Crohn's Disease [published correction appears in Crohns Colitis 360. 2025 Mar 25;7(1):otaf022. doi: 10.1093/crocol/otaf022.]. Crohns Colitis 360. 2024;6(4):otae060. Published 2024 Oct 24. doi:10.1093/crocol/otae060
4. Devi J, Xu A, Stone M, et al. Real-World Effectiveness and Safety of Upadacitinib in Crohn's Disease: A Multicenter Study. Clin Gastroenterol Hepatol. Published online March 8, 2025. doi:10.1016/j.cgh.2025.01.012

Introduction

In perianal fistulizing Crohn’s disease (PFCD), higher infliximab (IFX) serum trough concentrations are associated with improved outcomes. Most PFCD patients require dose intensification to achieve therapeutic target concentrations. IFX pharmacokinetics (PK) in PFCD have not been previously characterized. We hypothesized that IFX clearance (CL) is increased in PFCD compared to Crohn’s disease with luminal disease only (CD).

Aims & Methods

Patients with CD and PFCD starting standard-dose intravenous IFX (5 mg/kg at week 0, 2, 6, thereafter every 8 weeks) were enrolled. Pre-infusion samples were collected from week 2 to 26 to measure IFX trough levels (TL), and anti-drug antibodies if IFX TL was below 1.0 μg/mL. Target TL were 20 μg/mL (week 2), 15 μg/mL (week 6), and 10 μg/mL (week 14) for PFCD, and 5.0 μg/mL (week 14) for CD. A population PK model was constructed using nonlinear mixed-effects modeling and adjusted for clinically relevant covariates.

Results

A total of 148 patients were included (63 PFCD, 85 CD), contributing 761 serum samples. Baseline demographics were comparable, except for higher luminal disease activity and concomitant immunomodulator use in CD. During induction, target IFX TL were achieved in significantly fewer PFCD patients (43% vs. 57%, P = .038). At week 14, median IFX TLs were lower in PFCD (2.8 μg/mL [IQR 1.0-5.4] than in CD (4.8 μg/mL [IQR 2.0–6.6], P = .014), with target TL attainment in only 9% of PFCD versus 46% of CD patients (P < .001). In multivariate regression analysis, PFCD was independently associated with a sevenfold increased risk of underdosing at week 14 (adjusted risk ratio [aRR] = 7.14, P < .001). Anti-drug antibodies (ADA) against infliximab were detected in 10/19 (53%) of PFCD patients and 9/25 (36%) CD patients with IFX TL below 1 μg/mL (P = .36) after a median of 20 weeks, with 35% of cases being transient during follow-up. While more PFCD patients had very low infliximab levels at week 14 (<1 μg/mL; 22% vs. 10%, P = .07), ADA presence and median ADA levels at that time did not differ significantly between these groups (P = .99 and P = .25, respectively).
IFX PK was described by a two-compartment model with linear elimination. Population PK modeling of the first 14 weeks revealed an 18% increase in IFX CL among patients with active perianal fistulas adjusted for dose, weight, serum albumin and presence of anti-drug antibodies (P < 0.01).

Conclusion

Active perianal fistulas are independently associated with increased infliximab clearance in patients with Crohn’s disease, resulting in significantly lower and frequently subtherapeutic serum trough levels despite standard induction dosing. At week 14, patients with PFCD had a sevenfold higher risk of underexposure compared to those with luminal CD only. These findings highlight a critical need for intensified or personalized infliximab dosing strategies during induction in PFCD to optimize therapeutic exposure and improve clinical outcomes.

Introduction

Perianal fistulizing Crohn’s disease (pfCD) is a debilitating phenotype that severely impacts quality of life (QoL). pfCD frequently implies a stepwise, combined medical and surgical treatment approach. Treatment goals are ideally individual and include improvement of QoL, however precise outcomes are not determined yet. Currently, most commonly used outcomes are clinical response/remission, and radiological healing, the latter most relevant to long-term disease remission.

Aims & Methods

The aim of this study was to evaluate QoL in pfCD and compare it with clinical and radiological outcomes after 26 weeks of treatment.
In this prospective exploratory, observational cohort (AMFIBIO), we included patients with pfCD starting on anti-TNF-α therapy, mesenchymal stem cell injection (MST), or hyperbaric oxygen therapy (HBOT) combined with surgical closure. We collected patient-reported IBD-specific (IBDQ-32) and fistula-specific (CAF-QoL) QoL outcomes. MAGNIFI-CD (remission defined as MAGNIFI-CD ≤6), perianal disease activity index (PDAI; response defined as ≤4) and fistula drainage assessment (FDA) were evaluated at baseline and week 26. Paired T tests were used to analyze changes in QoL, clinical and radiological scores. Pearson’s correlation coefficients were used to correlate changes between the outcomes.

Results

Twenty-one patients were analyzed at week 26 (Table 1). Mean change between baseline and week 26 in CAF-QoL and IBDQ-32 was 13 (95%CI 3 – 23) and 9 (95%CI -5 – 24) respectively. FDA correlated moderately with improvement in CAF-QoL (ρ=0.59; 95%CI 0.19 – 0.82), and moderately with improvement in IBDQ-32 (ρ=0.49; 95%CI 0.04 – 0.77). Improvement in CAF-QoL (ρ=0.31; 95%CI -0.20 – 0.69) and IBDQ-32 (ρ=0.35; 95%CI -0.16 – 0.72) did not correlate with improvement in PDAI, nor with PDAI response (resp. ρ=0.38; 95%CI -0.009 – 0.71, and ρ=0.40; 95%CI -0.08 – 0.72). No correlation was seen between changes in CAF-QoL and MAGNIFI-CD (ρ=0.08; 95%CI -0.39 – 0.52), or MRI remission (ρ=0.22; 95%CI -0.26 – 0.61).

Table 1. Patient and fistula characteristics (n=21)

Conclusion

IBD- and fistula-specific Quality of Life scores improve after therapy at week 26 in patients with pfCD. This improvement correlates with fistula drainage assessment, however it does not correlate with PDAI and MRI outcomes.

Disclosure

LM, KB, JT and RvH have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this abstract. CB has received grants from Boehringer Ingelheim and Roche; speakers honoraria from AbbVie, Janssen, Galapagos, Takeda, and Tillotts. JS is President-elect of the European Society of Gastrointestinal and Abdominal Radiology. GD has served as consultant for AbbVie, Astrazeneca, Alimentiv, Bristol-Myers Squibb, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, Johnson and Johnson, Takeda, Pfizer Inc, Polpharma, Prometheus Biosciences, Tillotts and Ventyx; received speaker fees from AbbVie, Boehringer Ingelheim, Celltrion, Eli Lilly, Johnson and Johnson, Takeda, Pfizer Inc and Tillotts. KG has received grants from Pfizer Inc, Celltrion and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis and Takeda and speaker’s honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda and Tillotts.

Introduction

Short bowel syndrome (SBS) is a severe complication of extensive small intestinal resection, most commonly occurring in Crohn’s disease (CD), a chronic inflammatory disorder defined by transmural immune infiltration. Cytokines and chemokines are central mediators in the immune cascade driving intestinal inflammation and tissue damage^1,2. Despite advances in care, no biomarkers currently predict SBS onset or progression to intestinal failure (IF). Profiling systemic cytokine and chemokine signatures may thus offer novel insight into disease trajectory and risk stratification.

Aims & Methods

This study investigates circulating inflammatory mediators in patients with established IF/SBS and CD patients at high risk of progression. A total of 150 patients with CD were enrolled and stratified into five groups based on intestinal function and surgical history: A1, SBS with IF requiring parenteral nutrition (PN) or intravenous fluids; A3, SBS without IF and inactive disease; B, high risk of IF with multiple or extensive resections; C1, low risk for IF with no history of resection; and C2, low risk for IF with prior resection. Serum cytokine and chemokine profiles were quantified at baseline (T0) and after six months (T6) using the human 27-PLEX multiplex immunoassay.

Results

Serum cytokines and chemokines profiling at baseline (T0) and after six months (T6) revealed distinct inflammatory patterns across the study groups. Patients with SBS and IF (group A1) showed persistently elevated levels of IP-10, IL-12, MIP-1α, and G-CSF, reflecting sustained immune activation. Whereas, patients at high risk of IF (group B) displayed increased Eotaxin, bFGF, IL-15, and IL-6, indicative of subclinical inflammation and possible tissue remodelling.
A general reduction in cytokine levels was observed at T6, though anti-inflammatory mediators remained minimally modulated, suggesting ongoing low-grade inflammation. Comparisons between groups highlighted divergent cytokine signatures correlating with disease severity and nutritional support requirements.

Conclusion

These findings suggest that specific circulating cytokines may serve as potential biomarkers for early identification of patients at risk of IF. The differential expression patterns observed across groups support their relevance in stratifying disease severity in CD and SBS. Further large-scale studies are needed to validate these preliminary results and to fully establish their prognostic significance.
Funded by: 2.1 “Rafforzamento e potenziamento della ricerca biomedica del SSN”, finanziato dall’Unione europea – NextGenerationEU, CUP C53C22001140007. 2022 PNRR Project “Changing the future of intestinal failure in intestinal chronic inflammation: towards innovative predictive factors and therapeutic targets” code: PNRR-MAD-2022-12376791.

References

1. Friedrich M, Pohin M, Powrie F. Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. Immunity. 2019;50(4):992-1006. doi:10.1016/j.immuni.2019.03.017
2. Singh UP, Singh NP, Murphy EA, et al. Chemokine and cytokine levels in inflammatory bowel disease patients. Cytokine. 2016;77:44-49. doi:10.1016/j.cyto.2015.10.008

Introduction

Perianal fistulas occur in up to 30% of patients with Crohn’s disease (pfCD) and frequently require a combined medical and surgical treatment approach. Hyperbaric Oxygen Therapy (HBOT) has previously shown benefit in treatment-refractory pfCD.

Aims & Methods

In this pilot study, we aim to assess the feasibility of surgical fistula closure 4 weeks after HBOT, and efficacy of combining surgical closure and 8 weeks HBOT.
Patients with complex pfCD refractory to at least 6 months of anti-TNF therapy were included in this study. All patients received a seton prior to starting treatment with 40 sessions (8 weeks) of HBOT (each lasting 110 minutes, with 5-minute air breaks) with 100% oxygen at 2.4 atmosphere. At week 4 the seton was removed, and surgical closure of the internal fistula opening was attempted. All patients continued stable dose of medical treatment during the study. Response was assessed by the fistula drainage assessment (FDA) and the perianal disease activity index (PDAI) at week 9, 26 and 52, and by pelvic MRI at week 9 and 26. MRI response was defined as a decrease of 2 points in MAGNIFI-CD score, MRI remission as a MAGNIFI-CD ≤6. (Serious) Adverse Events (AE) were reported for 52 weeks. Univariate logistical regression was used to explore potential variates associated with PDAI response (≤4) at week 26.

Results

Ten patients completed treatment and were analyzed (Table 1). All patients completed HBOT and underwent a technically successful surgical procedure at week 4. No proctitis was encountered at week 4 during examination under anesthesia. PDAI response was achieved by 30%, 60%, 58% at week 9, 26 and 52, respectively. FDA response/remission was achieved in 50%/20%, 80%/40% and 80%/50% of patients at week 9, 26 and 52, respectively. MRI response/remission was achieved in 60%/10% and 60%/20% of patients at week 9 and 26, respectively. No significant parameters were associated with PDAI response at week 26 in univariate logistical regression. (S)AEs included one patient with a potential oxygen toxicity seizure without long term effects, and one patient reported claustrophobia, no new AEs were reported.

Table 1 Patient and fistula characteristics (n=10)

Conclusion

HBOT is feasible in combination with surgical therapy in patients with complex pfCD refractory to anti-TNF therapy. Patients had long-lasting benefit of the combined treatment approach. Further translational data are currently analyzed to clarify mechanisms of action and to explore potential biomarkers for therapy response.

Disclosure

LM, KB, JT and RvH have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this abstract. JS is President-elect of the European Society of Gastrointestinal and Abdominal Radiology. GD has served as consultant for AbbVie, Astrazeneca, Alimentiv, Bristol-Myers Squibb, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, Johnson and Johnson, Takeda, Pfizer Inc, Polpharma, Prometheus Biosciences, Tillotts and Ventyx; received speaker fees from AbbVie, Boehringer Ingelheim, Celltrion, Eli Lilly, Johnson and Johnson, Takeda, Pfizer Inc and Tillotts. CB has received grants from Boehringer Ingelheim and Roche; speakers honoraria from AbbVie, Janssen, Galapagos, Takeda, and Tillotts. KG has received grants from Pfizer Inc, Celltrion and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis and Takeda and speaker’s honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda and Tillotts.