Background: Perianal fistulizing Crohn’s disease (CD) is associated with significant morbidity and remains difficult to treat. Although advanced medical therapies are widely used, much of the available evidence derives from heterogeneous fistula populations or luminal CD trials, with limited perianal-specific synthesis and inconsistent outcome definitions. We conducted a systematic review focusing exclusively on perianal-specific clinical, radiologic, and composite outcomes in adults with perianal fistula (PAF) CD. Methods: We performed a systematic review in accordance with PRISMA 2020. Electronic databases were searched from inception through November 2025. We included randomized controlled trials and cohort studies enrolling adults with CD reporting outcomes specific to PAF. Interventions included biologics and small-molecule therapies, compared with placebo or other therapies. Due to substantial heterogeneity in outcome definitions and study designs, a meta-analysis was not performed. Risk of bias was assessed using Risk of Bias 2 (RoB 2) for randomized trials and the Newcastle–Ottawa Scale for observational studies. Results: Seven studies including >1200 participants with PAF-CD met inclusion criteria. Follow-up ranged from 24 weeks to 5 years. Across studies, outcome definitions and assessment modalities varied. Upadacitinib demonstrated significantly higher clinical fistula closure compared with placebo across multiple dose regimens at 52 weeks. In observational comparisons, ustekinumab and vedolizumab were associated with higher clinical closure rates than anti-TNF therapies. However, infliximab demonstrated higher closure rates than adalimumab as a first-line treatment. The definition for radiologic remission was less consistent across studies and often did not parallel clinical outcomes. Composite clinical–radiologic remission and response were reported in a limited number of studies, with filgotinib showing higher composite outcomes in comparison to placebo in a phase 2 trial. Surgical interventions, relapse outcomes, biomarkers [C-reactive protein (CRP)/fecal calprotectin (FCP)], and patient-reported outcomes were variably reported and not consistently significant across comparisons. Conclusions: Evidence for advanced therapies in PAF CD remains limited by heterogeneity in endpoint definitions, subjectivity in clinical observation, inconsistent radiologic reporting, and reliance on subgroup or observational comparisons. While anti-TNF therapy remains the most established option in guidelines, emerging data suggest significant benefits with ustekinumab, vedolizumab, and JAK inhibitors in selected patients. There is a need for PAF-specific, adequately powered randomized trials using standardized composite clinical and radiologic endpoints.

Takayasu arteritis (TAK) is a granulomatous large-vessel vasculitis typically affecting young adult females. Pediatric cases are rare, and infantile onset is exceptional. Management relies on immunosuppression, with surgery reserved for severe complications. We describe a now 5.5-year-old boy diagnosed with TAK at six months of age, presenting with hypertensive encephalopathy and kidney dysfunction. Despite treatment with corticosteroids and anti-TNFα, his kidney function deteriorated, leading to kidney failure and dialysis. At nearly three years of age, he underwent abdominal aorto-aortic bypass and bilateral nephrectomy due to progressive vascular narrowing and refractory hypertension. At age four, he successfully received a deceased-donor kidney transplant. Eighteen months post-transplant, he maintains excellent graft function and shows no signs of TAK recurrence. This case underscores the complexity of diagnosing and managing infantile TAK with multiorgan involvement. To our knowledge, he is among the youngest reported TAK patients to undergo successful kidney transplantation following major vascular surgery. His course demonstrates the potential for long-term remission and safe transplantation under standard immunosuppression, without continued anti-TNFα therapy. The literature is sparse regarding kidney failure and transplantation in TAK, particularly in infants. This case highlights key management dilemmas in infantile TAK, including clinical diagnosis, timing of surgery and transplantation, choice of immunosuppression, and long-term monitoring. It emphasizes the importance of a multidisciplinary approach and the need for collaborative research to address knowledge gaps in this rare but complex condition.

Perianal fistulising Crohn's disease (pfCD) remains a therapeutic challenge, with a limited sustained response to biological therapy. Although higher serum anti-tumour necrosis factor (TNF) levels are associated with improved fistula healing, tissue pharmacokinetics in pfCD are poorly understood. This proof-of-concept study aimed to establish the feasibility of quantifying anti-TNF concentrations within fistula tissue and evaluate their relationship with serum levels and treatment outcomes. Paired blood and fistula tract biopsies were obtained from 14 patients (infliximab, seven; adalimumab, seven) with active pfCD on established anti-TNF therapy (>14 weeks post-induction). The serum was processed by centrifugation within 8 h and stored at -80°C. Fistula tract biopsies were snap-frozen, homogenised, and extracted using an ELISA buffer proportional to tissue weight. Anti-TNF levels in the serum and tissue supernatants were quantified using standard and high-sensitivity ELISA assays, respectively. All patients had detectable anti-TNF concentrations in both serum and fistula tissues. Tissue and serum levels showed a moderate positive correlation (r = 0.45, P = 0.09), with a stronger and statistically significant association in the infliximab subgroup (r = 0.81, P = 0.01). Higher fistula-to-serum ratios, reflecting enhanced tissue penetration, tended towards improved clinical and radiological outcomes and lower perianal disease activity index scores, although the difference was not statistically significant. Anti-TNF levels in perianal fistula tissue are measurable and correlated with serum concentrations, supporting a mechanistic link between systemic exposure and local drug penetration. These findings highlight the feasibility of tissue-level pharmacokinetic assessments and warrant validation in larger prospective cohorts.

Background: Cytomegalovirus (CMV) reactivation is frequently observed in patients with moderate-to-severe ulcerative colitis (UC), particularly in steroid-refractory cases; however, the clinical significance of tissue CMV DNA detection by polymerase chain reaction (PCR) in the absence of classical histopathological findings remains controversial. Methods: This retrospective cohort study included 110 patients with moderate-to-severe UC who underwent colonoscopy between January 2021 and April 2024 at a tertiary referral center. Tissue and serum samples were analyzed for CMV DNA using PCR. Tissue CMV DNA positivity was defined as ≥250 copies. Endoscopic disease activity was assessed using the Mayo clinical score, Mayo endoscopic score, and the Rachmilewitz Endoscopic Activity Index. Associations between tissue CMV DNA positivity, endoscopic activity scores, inflammatory markers, recent immunosuppressive therapy, and serum CMV PCR results were evaluated. Sensitivity analyses using different tissue CMV DNA thresholds and receiver operating characteristic (ROC) curve analysis for serum CMV PCR were also performed. Results: Tissue CMV DNA positivity was detected in 37.3% of patients. Patients with tissue CMV DNA positivity had significantly higher Mayo clinical scores and Rachmilewitz Endoscopic Activity Index scores compared with CMV-negative patients, whereas Mayo endoscopic scores did not differ significantly between groups. Serum CMV PCR levels were markedly higher in patients with tissue CMV DNA positivity (p < 0.001). Tissue CMV DNA copy number showed a strong correlation with serum CMV PCR levels but did not demonstrate a consistent linear association with endoscopic activity scores. In multivariable logistic regression analysis, recent corticosteroid use was independently associated with tissue CMV DNA positivity, while anti-TNF therapy and endoscopic activity indices were not independent predictors. ROC analysis demonstrated good diagnostic performance of serum CMV PCR for predicting tissue CMV DNA positivity (AUC = 0.82). Conclusions: In patients with moderate-to-severe UC, tissue CMV DNA positivity (≥250 copies) is associated with increased clinical and endoscopic disease activity, even in the absence of classical histopathological evidence of CMV infection. These findings suggest that molecular detection of CMV in colonic tissue may provide clinically relevant information in selected patient populations, particularly those with recent corticosteroid exposure. However, tissue CMV DNA positivity should be interpreted as a molecular association rather than definitive evidence of causality or an indication for antiviral therapy. Prospective multicenter studies are warranted to further clarify the clinical implications of tissue CMV DNA detection in UC.

Perianal fistulising Crohn's disease (pfCD) is a heterogeneous phenotype of Crohn's disease with marked variability in anatomical complexity, symptomatology, and disease trajectory. This often creates uncertainty in the optimal approach to management, particularly the surgical aspects of when to perform examination under anaesthesia (EUA) and when to insert or remove setons. We conducted a systematic review following PRISMA guidelines. Multiple databases were searched from inception through December 2025. Eligible publications included clinical guidelines on pfCD and/or rectovaginal fistulas that reported indications for EUA, seton insertion, and/or seton removal. We stratified recommendations by fistula complexity, the presence of abscesses, and clinical symptoms. Risk of bias was assessed using the AGREE II Instrument. Twenty-four guidelines met inclusion criteria. EUA (and often seton placement) was universally recommended for perianal abscesses and frequently for symptomatic complex pfCD. For asymptomatic complex or symptomatic simple fistulas, recommendations were variable and often conditional on the presence of proctitis or plans for biologic therapy. In contrast, EUA and setons were not broadly endorsed for asymptomatic simple fistulas. Recommendations for seton removal varied widely, ranging from predefined intervals after anti-TNF therapy initiation to individualised criteria based on clinical or radiologic response. Most guidelines did not consider symptom type/severity, prior surgery, suitability for surgical closure, and asymptomatic abscesses detected by imaging. Substantial heterogeneity and limitations exist across guidelines on the surgical management of pfCD. This underscores the need for international consensus informed by multidisciplinary expertise to standardise care in this complex population.

Background: Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease frequently associated with hematological abnormalities such as anemia, thrombocytosis, and altered indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Anti-TNF therapy has revolutionized the treatment of AS, yet, the impact of anti-TNF therapy on hematological parameters in Iraqi patients remains underexplored. Objectives: to evaluate the effect of anti-TNF therapy on hematological parameters and disease activity in patients with AS at Merjan Teaching Hospital as well as documenting adherence, adverse events, and potential confounders. Methods: A prospective observational cohort study was conducted between January 2024 and July 2025, enrolling 85 biologic-naïve AS patients fulfilling modified New York or ASAS criteria. Patients received infliximab, adalimumab, or etanercept according to clinical judgment. Baseline and follow-up assessments included complete blood count (CBC), derived indices (NLR, PLR, SII), Erythrocyte Sedimentation Rate, c-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The statistical analyses were completed using paired t-tests, repeated measures ANOVA, correlation analysis and multivariate regression with adjustment for covariates. Results: The cohort comprised predominantly males (87%) with a mean age of 40.9 years. Baseline disease activity was high (mean BASDAI 6.26 ± 1.39; CRP 45.27 ± 44.61 mg/L; ESR 49.84 ± 15.28 mm/h). Anti-TNF therapy significantly reduced BASDAI, ASDAS, CRP, and ESR over 12 weeks. Hematological improvements included increased hemoglobin, reduced platelet counts, and normalization of NLR and PLR. Adherence exceeded 80%, with minor adverse events reported; no severe hematological toxicities occurred. Conclusions: Anti-TNF therapy in Iraqi AS patients effectively improved disease activity and corrected hematological abnormalities. Indices such as NLR and PLR may serve as reliable biomarkers of treatment response, underscoring the dual clinical and hematological benefits of biologic therapy in AS management.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis are emerging extraintestinal manifestations of inflammatory bowel disease (IBD), but their true burden and the impact of therapies on liver health have not been fully elucidated. We aimed to assess the prevalence of hepatic steatosis and fibrosis in IBD versus matched controls and examine associations with therapies, particularly anti-TNF agents and corticosteroids. In this cross-sectional study, 358 adults with IBD and 358 controls individually matched for age, sex, BMI, and diabetes underwent vibration-controlled transient elastography (VCTE; FibroScan). These are the baseline findings of the ongoing ELASTIBD cohort. Patients with IBD had higher rates of significant fibrosis (12.3% vs. 4.2%; adjusted odds ratio [aOR] 3.31 and 95% CI 1.75-6.26), advanced fibrosis (6.7% vs. 0.6%; OR 8.50 and 95% CI 1.98-36.52), and steatosis (41.4% vs. 28.3%; aOR 2.51 and 95% CI 1.66-3.79) than controls. Among patients with IBD, anti-TNF therapy was less frequent in those with fibrosis (44.4% vs. 68.5% and p=0.004) and independently associated with lower odds of fibrosis (aOR 0.39 and 95% CI 0.16-0.95), whereas each steroid course was associated with 41% higher odds (aOR 1.41 and 95% CI 1.04-1.92). Older age and higher BMI were additional predictors. Patients with IBD demonstrated threefold higher fibrosis and twofold higher steatosis than matched controls, emphasizing the importance of liver assessment in clinical practice. The inverse association between anti-TNF exposure and fibrosis suggests inflammation control may reduce hepatic fibrogenesis and supports follow-up of the ELASTIBD cohort to clarify progression, treatment effects, and liver outcomes.

Inflammatory bowel disease (IBD) is associated with an increased risk of major adverse cardiovascular events (MACE). Janus kinase inhibitors (JAKi) are approved to treat IBD, but there are concerns over whether they increase the risk of MACE or venous thromboembolism (VTE) in patients with IBD. We aimed to compare the incidence risk of MACE and VTE in patients with IBD treated with JAKi agents versus anti-TNFs. We conducted a retrospective cohort study using the TriNetX database to identify patients ≥ 18years with IBD and treated with JAKi or anti-TNF therapy. Patients in the JAKi cohort were matched with patients treated with anti-TNF by using 1:1 propensity score matching. Patients with a history of a prior cardiovascular event were excluded from the analysis. Co-primary outcomes were MACE and VTE within 1-year after medication initiation. Additional subgroup analyses were performed based on age, sex, and IBD type. Kaplan-Meier analysis with adjusted hazard ratios (HRs) and 95% CIs were used to compare time-to-event rates. In total, there were 8942 patients in the JAKi cohort matched with 8942 patients in the anti-TNF cohort. There was no difference between the two cohorts in the development of MACE (aHR: 1.08; 95% CI: 0.87-1.33; p = 0.49) or VTE (aHR: 1.06; 95% CI: 0.84-1.36; p = 0.61). In patients aged ≥ 65years, there was no statistically significant difference between the two cohorts in MACE outcomes (aHR: 0.95; 95% CI: 0.69-1.31; p = 0.75). Consistent findings were observed when comparing ulcerative colitis to Crohn's disease, upadacitinib to tofacitinib, or JAKi to infliximab. Our results suggest that patients with IBD, including patients ≥ 65years, who are treated with JAKi, were not at increased risk of MACE or VTE over a 12-month period as compared to those treated with anti-TNF therapy. Further prospective studies are warranted to confirm these findings.

Autoimmune-related events following anti-tumor necrosis factor alpha (anti-TNF-α) therapy are increasingly reported, but population-level data on new-onset autoimmune disease in inflammatory bowel disease (IBD) remain limited. We evaluated whether anti-TNF-α exposure is associated with autoimmune disease development in IBD. We conducted a nationwide population-based case-control study using data from the Korean National Health Insurance Service database (2004-2018). Patients with IBD who developed new-onset autoimmune diseases, including psoriasis, interstitial lung disease (ILD), systemic lupus erythematosus, systemic vasculitis, and central nervous system disorders, were matched 1:1 to controls by age, sex, diagnosis year, and IBD subtype. Logistic regression with propensity score matching and spline modeling was used to assess associations, including subgroup and sensitivity analyses. Among 8,586 matched pairs, anti-TNF-α therapy was associated with increased risks of autoimmune disease (adjusted odds ratio [aOR], 1.65), particularly psoriasis (aOR, 1.58) and ILD (aOR, 1.88). A non-linear dose-response relationship was observed: the risk rose sharply at early exposure, plateaued at approximately 30 prescriptions, and gradually declined beyond 64. This association remained regardless of prior immunosuppressant use and was attenuated but significant in immunosuppressant users with psoriasis. No significant associations were found for systemic lupus erythematosus, central nervous system disorders, or vasculitis. Patients receiving prolonged concomitant therapy ( ≥ 90 days) showed increased risk (aOR, 1.43). Monotherapy showed a non-significant trend (aOR, 1.19). Anti-TNF therapy for IBD is associated with an increased risk of developing new-onset autoimmune diseases, especially psoriasis and ILD. Careful monitoring is warranted, particularly in patients receiving prolonged or combined immunosuppressive therapies.

Background: Antitumor necrosis factor (anti-TNF) agents are associated with an increased risk of Clostridioides difficile ( C. difficile ) infection (CDI). The risk associated with Ustekinumab (UST) in real-world clinical practice remains poorly defined. Objectives: To compare the incidence densities (IDs) and risks of CDI and C. difficile nucleic acid positivity ( C. difficile positivity) between patients with Crohn’s disease (CD) initiating UST and those initiating anti-TNF therapy. Design: Single-center retrospective cohort study. Methods: In a retrospective cohort study, we included 627 CD patients with a negative baseline C. difficile nucleic acid test who initiated UST or anti-TNF therapy between November 2020 and October 2024. IDs and incidence density ratios (IDRs) were calculated. Hazard ratios (HRs) for CDI and C. difficile positivity were estimated using marginal structural models based on Cox regression. Results: The cohort included 277 patients (381 person-years, PY) treated with UST and 350 patients (454 PY) treated with anti-TNF agents. CDI developed in 4 of 277 UST-treated participants (1.05/100 PY) and 9 of 350 anti-TNF-treated participants (1.98/100 PY), corresponding to an IDR of 0. 53 (95% confidence interval (CI): 0.14–1.99, p = 0.347). C. difficile positivity was recorded in 12 of 277 participants, compared with 25 of 350 participants, corresponding to IDs of 3.15 and 5.50/100 PY, respectively (IDR = 0.57, 95% CI: 0.27–1.19, p = 0.137). After adjustment, no significant differences were observed in the risk of CDI (HR = 0.51, 95% CI: 0.16–1.17, p = 0.274) or C. difficile positivity (HR = 0.59, 95% CI: 0.29–1.21, p = 0.151). An exploratory sensitivity analysis in biologic-naïve patients yielded an adjusted HR of 0.27 (95% CI: 0.05–1.30), which did not reach statistical significance ( p = 0.102). Conclusion: In this real-world cohort, treatment with UST was not associated with a significantly higher risk of CDI or C. difficile positivity compared to anti-TNF therapy. The consistent direction of point estimates, suggesting a potential risk reduction especially in biologic-naïve patients, remains exploratory and warrants further investigation in larger studies.

Abstract Background Acquired hemophilia A (AHA) has never been reported in patients with pediatric inflammatory bowel disease (IBD). Aims We describe a case of AHA occurring in an adolescent with ulcerative colitis treated with infliximab. We hypothesize that in rare circumstances, anti-TNF therapy can trigger factor VIII inhibitor development in patients with IBD. Methods We reviewed the disease course of an adolescent with ulcerative colitis who developed AHA after 3 years of infliximab therapy. A focused literature review was performed to assess reports of inflammatory bowel disease and AHA. Results The patient presented at 14 years of age with a 3-month history of bloody diarrhea and raised serum and fecal biomarkers. His colonoscopy showed a Mayo 2 pancolitis. After a course of oral prednisone, he was commenced on infliximab monotherapy in September 2022. He achieved sustained clinical remission with normal serum and fecal biomarkers. Repeat scope in July 2024 showed endoscopic and histologic remission. Intestinal ultrasound in July 2025 showed transmural remission. In July 2025, he presented with spontaneous bruising and palpable purpura on his legs. Laboratory investigations revealed a prolonged aPTT, factor VIII activity &amp;lt;0.01 IU/mL, and a high-titer inhibitor (49 BU), consistent with AHA. Malignancy, infection, and systemic autoimmune disease were excluded. He was treated with recombinant activated factor VII, emicizumab, high dose prednisone plus rituximab. Infliximab was discontinued. Over four weeks he had no further bruising episodes, factor VIII levels improved (to 0.16 U/mL) and inhibitor titer decreased (to 1 BU). He remains on emicizumab, continues to wean prednisone, and will commence an alternate pathway advanced therapy in the next month. He remains in clinical, serum and fecal biomarker remission with transmural remission on intestinal ultrasound. A Literature review confirmed four adalimumab-associated AHA cases. Infliximab has not previously been associated with AHA. Moreover, there have been no prior pediatric IBD reports of AHA. Conclusions This case represents the first pediatric report of infliximab-associated AHA in ulcerative colitis. It expands the spectrum of paradoxical autoimmune complications of anti-TNF therapy in IBD. Gastroenterologists should suspect AHA in IBD patients presenting with unexplained bleeding and prolonged aPTT, even in the context of disease remission. Early recognition and multidisciplinary management are essential to avoid morbidity and guide safe transition to alternate pathway advanced IBD therapies. Funding Agencies None

Abstract Background Both primary and secondary loss of response to therapy is a frequent occurrence in patients with inflammatory bowel disease (IBD). Frequently, practitioners must initiate advanced therapies due to flares of active IBD. Following addition of therapy, it is important to gauge both clinical and endoscopic response. In 2015, the STRIDE (Selecting Therapeutic Targets in Inflammatory Bowel Disease) working group recommended a shift from clinical definitions of remission to a more stringent endpoint requiring resolution of subclinical inflammation (i.e. endoscopic remission). Specifically, it is recommended to routinely evaluate for endoscopic remission within 6 to 9 months of treatment initiation in patients who have achieved clinical remission but not endoscopic remission, to prevent long-term complications. These recommendations were re-emphasized in a 2020 update (STRIDE-II). Assessment of endoscopic response is essential, as mucosal healing is an important treatment endpoint which may not always correlate well with clinical symptomology. Ideally, endoscopic reassessment is performed within one year of therapy modifications. However, often endoscopic reassessment may be delayed owing to multiple patient and systemic factors. Aims This study aimed to examine the frequency with which endoscopic reassessment is performed within one year of initiation of advanced therapy for IBD. Methods This study was performed using retrospective electronic chart review of patients at Vancouver General Hospital (VGH) with a diagnosis of CD or UC. Data was collected on patient demographics, disease phenotype, date of initiation of advanced therapy and date of endoscopic reassessment following initiation of advanced therapy. Results Data was collected on a representative sample of 50 patients. Of this sample, 18 patients had a diagnosis of CD, and 32 patients had a diagnosis of UC. 25 patients were on anti-TNF therapy, 14 patients were on anti-integrin therapy, 5 patients were started on anti-IL 23 therapy and 5 patients were on oral small molecule therapy. 17 patients had undergone endoscopic reassessment within one year of initiation of advanced therapy. 15 of the endoscopies were colonoscopies and 2 were flexible sigmoidoscopies. In total, endoscopic reassessment only occurred in 34% of patients within one year following initiation of advanced therapy. Conclusions Endoscopic reassessment of intestinal mucosa following initiation of advanced therapy is an important element in optimizing patient outcomes in IBD. In this representative sample, we identified that this practice only occurs in approximately 1/3 of patients following initiation of advanced therapy. Efforts should be made to prioritize more prompt endoscopic reassessment of patients following initiation of advanced therapy. Barriers to this endpoint should be further explored in future studies. Funding Agencies None

Abstract Background Ileal pouch-anal anastomosis (IPAA) is the standard surgical approach for ulcerative colitis. Complications associated with IPAA, including pouchitis, strictures, and fistulas pose major risks for morbidity, diversion, and IPAA failure. However, the impact of fistulas on IPAA outcomes are poorly understood. Aims To determine the cumulative incidence of IPAA associated fistulas (IAFs), and to determine if they are associated with adverse IPAA outcomes. Methods We performed a retrospective cohort study of adults with inflammatory bowel disease (IBD) who underwent IPAA and were followed at The Ottawa Hospital (2005-2024). Fistulas were classified as perianal, rectovaginal, or pouch-body, and as early (&amp;lt;6 months) or late (&amp;gt;6 months) post-ileostomy closure. Kaplan-Meier methods estimated cumulative incidence of fistula formation, fecal diversion, and pouch excision. Cox proportional hazards models adjusted for age, sex, luminal Crohn’s-like phenotype, and rectal stricture to evaluate the association between IAFs and pouch failure, a composite of fecal diversion or pouch excision. Fistula remission was defined clinically as absence of drainage without diversion. Results We identified 332 patients with IPAA: 48.8% female, mean age 33 ± 13 years. The cumulative risk of developing a IAF was 3.1%, 8.4%, 13.8%, and 29.8% at 1, 5, 10, and 20 years, respectively (Figure 1). The types of fistulas included perianal (55.8%), rectovaginal (37.7%), and pouch-body (6.5%). After a mean follow-up of 15.5 ± 9.9 years, PAFs were strongly associated with pouch failure (aHR, 7.1; 95% CI 3.3-15.5) including fecal diversion (aHR, 5.3; 95% CI 2.2-12.5) and pouch excision (aHR, 9.9; 95% CI 3.2-31.0). Following fistula diagnosis, 70% received an advanced therapy, most often anti-TNF therapy (87%). Fistula remission without fecal diversion occurred in 37.5% at 3 months, 39.6% at 6 months, and 41.7% at 12 months after first-line advanced therapy; 27.1% remained in remission at final follow-up. Conclusions In this single center study, we found that 14% of patients developed an IAF within 10 years and that fistulas were significantly associated with IPAA failure. These findings highlight the need for early detection, multidisciplinary care, and development of targeted therapies for fistulizing pouch disease. Funding Agencies None

Can we cure autoimmunity?

Abstract Background Oral Crohn’s disease (OCD) is a rare and debilitating extraintestinal manifestation characterized by painful ulcers, mucosal edema, and granulomatous inflammation of the face and/or mouth. Evidence guiding management remains limited, particularly for patients with refractory disease or anti-tumor necrosis factor-a (anti-TNF) therapy failure. Aims Given the limited existing literature, we aimed to describe the use and effects of non-anti-TNF based therapies in OCD. Methods Patients with histologically confirmed OCD treated with non-anti-TNF advanced therapies seen at two academic hospitals affiliated with Western University were identified. Data, including demographics, disease duration, treatment regimens, and longitudinal oral disease outcomes, were collected and summarized. Results Three female patients with histologically-confirmed OCD were identified. The median disease duration was 33 years (interquartile range, IQR=14 years). All had concomitant and severe intestinal disease at presentation, requiring a minimum of 2 surgeries over their disease course with a median time to first CD-related surgery of 2 years (IQR=5 years). All had anti-TNF exposure with secondary loss of response. Two of 3 patients experienced major anti-TNF adverse events (paradoxical psoriasis, septic arthritis) while on therapy. All patients had significant OCD involving, at minimum, the tongue, palate, buccae, with significant symptomatic burden. Median time to OCD diagnosis was 32 years (IQR=6.5 years). One patient developed OCD within 15 months of anti-TNF discontinuation, while two patients developed OCD while on treatment with an anti-TNF. Following the introduction of non-anti-TNF advanced therapies, all patients achieved complete resolution of OCD lesions with a median time to resolution of 6 months (IQR=5months). One patient achieved complete remission of oral lesions on high-dose vedolizumab. The second patient demonstrated full oral mucosal resolution on standard-dose risankizumab, and the third experienced a dose-dependent clinical response to upadacitinib, with recurrence of her oral disease upon dose de-escalation and recovery after re-escalation. All patients received concurrent oral dexamethasone mouth rinses, with only one patient receiving concurrent systemic glucocorticoid treatment (budesonide). No significant adverse events were observed during a one-year follow-up period. Conclusions This case series underscores a possible role for non-anti-TNF advanced therapies for the management of OCD. Herein, we highlight the successful use of α4β7-integrin blockade, IL-23 inhibition, and JAK inhibition for the management of this rare, but debilitating CD phenotype. These findings are hypothesis-generating. Further prospective studies are warranted to clarify long-term efficacy, durability of remission, and optimal treatment sequencing for non-anti-TNF therapies in OCD. Funding Agencies None

Abstract Background Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) with a rising prevalence in Canada. The cornerstone of CD therapy is biologic treatment; however, one-third of patients initiated on biologics fail to achieve steroid-free remission within one year. A Clinical Decision Support Tool (CDST) has been previously developed to predict outcomes and guide clinical management for patients on vedolizumab for CD; however, its broader applicability remains unclear. Aims To evaluate whether the CDST can identify CD patients at highest risk of health service utilization following biologic initiation. Methods A retrospective chart review was conducted at a large tertiary care referral academic center. Patients aged 18 years or older with CD who initiated biologic therapy between January 1, 2015, and December 31, 2023, were included. Patients with fewer than one follow-up appointment by December 31, 2024, were excluded. Outcomes included emergency department (ED) visits, hospital admissions, need for surgery, and development of fistulas or strictures, recorded up to December 31, 2024. CDST scores were assigned as follows: no prior bowel surgery (+2 points), no prior anti-TNF therapy (+3 points), no prior fistulizing disease (+2 points), baseline albumin (+0.4 per g/L), and baseline C-reactive protein (CRP: &amp;lt;3 mg/L = 0 points; 3–10 mg/L = −0.5 points; &amp;gt;10 mg/L = −3 points). Patients with &amp;lt;13 points were predicted to have a low likelihood of response, 15–19 points an intermediate likelihood, and &amp;gt;19 points a high likelihood. Chi-square analysis was used to analyze the data. Results A total of 138 CD patients initiating biologic therapy were included: 11 in the low group, 44 intermediate, and 83 high. The mean age across groups was similar (50.2 vs. 46.3 vs. 48.8 years). Compared to those with high CDST scores, patients with low and intermediate scores had higher hospitalization rates (45.5% vs. 22.7% vs. 7.2%, p &amp;lt; 0.001) and were more likely to discontinue biologic therapy (45.5% vs. 22.7% vs. 13.3%, p = 0.027). A trend toward significance was observed between CDST scores and ED visits (18.8% vs. 6.8% vs. 2.4%, p = 0.07). In the limited follow-up period, there appeared to be no significant associations between CDST score and development of penetrating or stricturing complications, or need for CD surgery. Conclusions CDST scores may predict hospitalization and discontinuation of biologic therapy in CD patients. This tool may help clinicians identify individuals at higher risk for treatment failure, enabling personalized management and closer monitoring. Funding Agencies None

Aim This study aimed to compare the effects of disease-modifying antirheumatic drugs (DMARDs) and anti-tumor necrosis factor (anti-TNF) therapy on inflammatory markers, lipid profile, and insulin resistance in rheumatoid arthritis (RA) patients, and to evaluate the potential cardiovascular impact of biological treatments. Material and Method This single-center, prospective study included 122 participants between May 2012 and May 2013: 35 RA patients treated with DMARDs, 31 RA patients treated with anti-TNF agents, and 56 healthy controls. Inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF)], lipid profile [total cholesterol, triglycerides, high-density lipoprotein (HDL), atherogenic index of plasma (AIP)], and glycemic parameters [fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR)] were assessed. Results ESR and CRP levels were significantly higher in RA groups compared with controls (p&amp;lt;0.001), and CRP was higher in the anti-TNF group than in the DMARD group. RF positivity was markedly increased in RA patients (p&amp;lt;0.001). No significant differences were found among groups for lipid profile or AIP (p&amp;gt;0.05). Insulin and fasting glucose levels were similar, while HOMA-IR was higher in controls and marginally lower in RA groups (p=0.049). Conclusion RA patients exhibited significantly elevated inflammation, whereas lipid profile and AIP did not differ between treatment groups. Suppression of inflammation was associated with partial improvement in insulin resistance. Cardiometabolic risk in RA should be assessed by considering not only conventional lipid parameters but also inflammation and insulin resistance as multifactorial determinants.

Background and Objectives: Biological therapies improve disease severity and quality of life in patients with psoriasis, but data on Romanian patients remain limited. Our study aimed to characterize patients with psoriasis from Transylvania and to evaluate the impact of biologics on disease severity, treatment switching, affected special areas response, quality of life, and laboratory biomarkers. Materials and Methods: We conducted a retrospective exploratory study at two centers in Cluj-Napoca, Romania, using routinely collected medical data. Results: One-hundred and fifteen patients (aged 2-72 years) were evaluated; 45 patients received anti-TNF, 43 received anti-IL-17, and 27 received anti-IL-23. Patients treated with anti-IL-17 or anti-IL-23 were older at diagnosis than those treated with anti-TNF (p = 0.0001). Psoriatic lesions were prevalent in the scalp (58.3%) and nails (36.5%). Methotrexate was the most common prior systemic therapy (87.8%), with no difference between the groups (p = 0.7668). Patients receiving anti-TNF therapy (46.7%) or anti-IL-17 therapy (20.9%) also most frequently received prior treatment with systemic retinoids. Cardiometabolic comorbidities, including hypertension (40.9%) and diabetes mellitus (20.9%), were prevalent. Anti-IL-17 therapies were used more frequently in patients with hypertension (46.5%), diabetes mellitus (34.9%), and psoriatic arthritis (34.9%). Baseline severity scores were comparable across the groups (p > 0.10). A therapeutic switch occurred in approximately one-quarter of the patients, most frequently in the anti-TNF group (57.8%), which also showed higher PASI and DLQI scores at switching (p < 0.0001). At 36 weeks, anti-IL-17 and anti-IL-23 therapies demonstrated superior outcomes compared to anti-TNF therapy (p = 0.045). All patients receiving anti-IL-23 therapy achieved a PASI 100 at the 60-week follow-up. Significant improvements in PASI and DLQI were observed for all biologics (p < 0.0001). Conclusions: Biological therapies were associated with significant improvements in disease severity and quality of life. Anti-TNF therapies were switched more frequently due to reduced efficacy, while clinical improvement was observed regardless of lesion localization.

Rheumatoid arthritis (RA) is characterized by joint inflammation and bone erosion. Understanding cytokine pathways, particularly those targeting TNF, is crucial for understanding pathology and advancing treatment development. Arid5a is a noncanonical RNA binding protein (RBP) that augments inflammation through stabilizing proinflammatory mRNAs and enhancing protein translation. We examined published datasets for ARID5A in human RA blood, T cells, and synovial tissues. A stromal cell line, epithelial cells, and primary synovial fibroblasts were used to assess the effect of TNF on Arid5a expression, localization, and function. To determine how TNF induces Arid5a, WT or Traf2-/- stromal cells were treated with NIK or IKK inhibitors. To evaluate the necessity of Arid5a in arthritis progression, Arid5a-/- mice were subjected to collagen-induced arthritis. ARID5A was elevated in patients with RA and reduced by anti-TNF therapy. TNF upregulated Arid5a through the NF-κB1/TRAF2 pathway, causing cytoplasmic relocalization. Arid5a stabilized proinflammatory transcripts and enhanced expression of chemokines that drive RA. Arid5a-/- mice were resistant to collagen-induced arthritis correlating with reduced Th17 cells in synovial tissue. Thus, Arid5a serves as a newly recognized signaling intermediate downstream of TNF that is elevated in human RA and drives pathology in murine CIA, potentially positioning this RBP as a possible therapeutic target.

Abstract Background and Aims Pyoderma gangrenosum (PG) is a rare but challenging extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), affecting 6–48% of IBD patients. This retrospective study analyzes affected patients and evaluates therapeutic strategies for both IBD remission and PG resolution. METHODS A multicenter retrospective analysis was conducted on patients with IBD and PG in 8 tertiary centers in Germany and Austria. Demographic data, prior therapies, surgeries, treatment of PG were collected, and treatment responses assessed. RESULTS The cohort included 50 patients (median age: 43 years; 68% female). Crohn’s disease (CD) was present in 58%, ulcerative colitis (UC) in 42%. Fifty percent of patients had prior surgery, 68% having an intestinal stoma. 48% were experienced to biologic therapy, predominantly anti-TNF therapy (83%). PG mainly affected the lower extremities (52%) and peristomal areas (24%). Systemic steroids were used in 52% of patients and led to PG resolution in only 12%. Anti-TNF therapy was the main approach, used in 68% of patients, with resolution achieved in 80%. Calcineurin inhibitors were given to 26% of patients and induced resolution in 38%. Three of six non-responders were successfully switched to infliximab. Overall PG resolution was achieved in 80%, correlating with IBD remission in 78%. The median time to PG resolution was five months. CONCLUSION Anti-TNF therapy was an effective treatment for PG in IBD patients, even in those with prior non-response to calcineurin inhibitors. Systemic steroids showed low response rates. PG healing mostly aligned with IBD remission, underlining the need for tailored long-term therapy.