Extraintestinal Manifestations In Patients Research Articles

P1243 Extraintestinal Manifestations in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Study in Taiwan

Abstract Background Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is rare in Taiwan. There are also few reports on the the prevalence rate of extraintestinal manifestations (EIMs) in IBD. This study aimed to assess the risk of EIMs in patients with IBD and examine the relationship between the timing of IBD diagnosis and EIM onset. Methods We conducted a retrospective cohort study using administrative data from the Taiwan National Health Insurance Research Database and Registry for Catastrophic Illness Patients Database from 2013 to 2021. The index date for the cohort was defined as the date of the first recorded IBD diagnosis. EIM diagnoses were identified in the health registry using the appropriate International Classification of Diseases 9 and 10 codes. The selection of EIMs refers to 2024 European Crohn's and Colitis Organisation (ECCO) guidelines, of which include uveitis, scleritis, episcleritis, Oral manifestations, PSC, AIH, spondyloarthropathy with axial/non-axial, pyoderma, gangrenosum, erythema nodosum, and Sweet syndrome1. We calculated the mean and median time of EIM onset relative to IBD and categorizing EIMs as occurring either before or after IBD onset. Results The study included 1,774 IBD patients. The incidence rate (IR) of EIMs in IBD patients was 1.167 per 100 persons/years from 2013 to 2021. The highest IR was 2.105 in 2013, and the lowest was 0.357 in 2021. The rate of EIMs development among IBD patients during the follow-up period from 2013 to 2019. Pyoderma had the highest IR at 0.846 per 100 persons/year, followed by primary sclerosing cholangitis at 0.733 per 100 persons/years, oral mucosa lesion at 0.733 per 100 people and ankylosing spondylitis at 0.564 per 100 persons/years (table1). Our analysis showed that EIMs appeared an average of 2.08 years after IBD diagnosis (median 1.48 years) and 5.50 years before IBD diagnosis (median 5.46 years). Conclusion We firstly reported the EIM risk by 1.167 per 100 persons/years in a relative low prevalence country. However, some classical EIMs mentioned in the 2024 ECCO guidelines do not occur as frequently among IBD patients in Taiwan as expected. We still need further investigation in this issue. We can extend the follow-up period to collect more data, which will allow us to reach a more solid and reliable conclusion.

P1134 The effectiveness of medical therapies for dermatological extraintestinal manifestations in patients with IBD: an umbrella review

Abstract Background Patients with IBD can develop various extraintestinal manifestations (EIMs), including those affecting the skin. These dermatological EIMs may or may not mimic the disease course of the underlying IBD, can have a significant impact on quality of life for patients and a major influence on treatment decisions. We conducted an overview of systematic reviews (umbrella review) to assess the effectiveness and safety of medical treatments for managing dermatological EIMs in patients with IBD. Methods In this umbrella review, we searched major databases (MEDLINE, Embase and Cochrane CDSR,) for relevant systematic reviews published until May 2024, that aimed to review the medical interventions of the dermatological EIMs. Screening, data extraction, and quality appraisal (using AMSTAR 2) were performed by at least two reviewers and any discrepancies resolved by a third independent reviewer. Results Of 1436 screened papers, 11 systematic reviews met our inclusion criteria. These 11 systematic reviews evaluated the effect of medical therapies across five dermatological EIMs in patients with IBD, with some systematic reviews considering more than one EIM: psoriasis (n=2), erythema nodosum (n=3), pyoderma gangrenosum (n=7), Sweet’s syndrome (n=1) and cutaneous vulval Crohn’s disease (n=1) (Table 1). For psoriasis, low response (14%) was reported to methotrexate but with high levels of remission with ustekinumab (82%), and no additional benefit of methotrexate combination with ustekinumab. For erythema nodosum, high levels of response were reported for anti-TNF therapies (80-100%), vedolizumab (50-62%) and ustekinumab (70%). For pyoderma gangrenosum, a more variable response was reported for anti-TNF therapies (21-92%), vedolizumab (33%) and ustekinumab (75%). For Sweet’s syndrome corticosteroids were reported to be effective in most, with limited data on more advanced therapies. For cutaneous vulval Crohn’s disease metronidazole was associated with 23% complete healing with limited data on more advanced therapies. There were no published systematic reviews on effectiveness of IL-23 specific p40 antagonists or oral small molecules. Effectiveness data was mostly descriptive and generally high levels of response were reported to the above treatments. Overall the certainty in the results of the reviews was low. Conclusion Although dermatological manifestations are common for patients with IBD, the evidence-base for medical interventions to treat these dermatological EIMs is limited and heterogeneous. These results outline the need for dedicated research studies to better determine the effectiveness and safety of medical therapies to treat dermatological manifestations specifically in patients with IBD.

Prevalencia de manifestaciones extraintestinales y otras condiciones asociadas en una cohorte de pacientes con enfermedad inflamatoria intestinal de un centro avanzado en Bogotá, Colombia

Introduction and aimsThe prevalence and incidence of inflammatory bowel disease (IBD) has increased significantly in Latin America. Extraintestinal manifestations (EIMs) have elevated morbidity and are poorly characterized in the region. Our aim was to describe the characteristics of EIMs in patients with IBD at the Hospital Universitario Fundación Santa Fe de Bogotá, utilizing the EIM classification proposed by the European Crohn's and Colitis Organisation (ECCO). Materials and methodsA cross-sectional study was conducted based on an institutional database of patients with IBD and the EIM definition used by the ECCO. Prevalence and prevalence ratios (PRs) of the EIMs were calculated. ResultsThe study included 168 patients, 66 of whom were diagnosed with Crohn's disease (CD) and 102 with ulcerative colitis (UC). A total of 30.4% patients had at least one EIM, and the most frequent were oral ulcers (13.7%), arthritis (10.1%), and uveitis/episcleritis (6.5%). There was a greater prevalence of EIMs in CD (31.8% vs 29.40% in UC) and women (32.47% vs 28.57% in men). There was a significant PR between uveitis/episcleritis and arthritis, erythema nodosum and arthritis, and erythema nodosum and other eye diseases. ConclusionsOur study shows a high prevalence of EIMs, surpassing that of previous Colombian studies, with a predominance of CD. Oral manifestations stand out as the most common. Prevalence studies on EIMs in Colombia are needed to establish multidisciplinary specialized centers, improving the quality of life of patients with IBD.

Ulcerative colitis and autoimmune uveitis. Case report

The article provides information on the pathogenesis, classification and frequency of ophthalmic extra-intestinal manifestations in patients with inflammatory bowel diseases (IBD). A clinical observation of a patient with autoimmune uveitis and IBD is described, demonstrating the importance of early diagnosis of immuno-inflammatory diseases in the implementation of multidisciplinary management of patients with IBD and extraintestinal manidestations. The use of genetically engineered biological drugs helps to control the course of IBD, ophthalmic manifestations and prevents the development of complications.

Association between celiac disease and fibromyalgia and their severity: a cross-sectional study.

Fibromyalgia (FMS) is a common musculoskeletal disorder with many causes. People with fibromyalgia often have the same symptoms as people with celiac disease (CD). Demonstration of the coordination and frequency of FMS and CD is important for effective treatment. This is a single center cross-sectional clinical study. The study included 60 patients who were diagnosed with CD by the Gastroenterology Clinic based on American College of Gastroenterology (ACG) criteria. Patients were also asked to complete the Widespread Pain Index (WPI), Symptom Severity Scale (SSS), and Fibromyalgia Impact Questionnaire (FIQ) to diagnose fibromyalgia and assess its severity. The results were used to analyze the frequency of concomitance and relationship between the two diseases. The relationship between the clinical types of CD and the presence of fibromyalgia was insignificant. Analysis of the relationship between the pathologic typing of biopsy and fibromyalgia frequency was insignificant. Those with antibodies more frequently met criteria for fibromyalgia (P = 0.04, P = 0.04, respectively). Presence of clinical extraintestinal manifestations in patients with CD should lead clinicians to consider FMS as a possible diagnosis. This points to the importance for clinicians in all subspecialties to be aware of the various symptoms and diseases associated with FMS.

Determination of the frequency of extraintestinal manifestations in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is a systemic disease whose etiology and pathogenesis are not fully understood and that affects organs and systems other than the gastrointestinal system. Many patients with IBD can develop extraintestinal manifestations (EIMs), affecting numerous organs and systems. The medical records of IBD patients followed in our gastroenterology clinic were retrospectively examined. While patients with Crohn's disease (CD) were grouped by anatomical site and clinical type, patients with ulcerative colitis (UC) were grouped by anatomical site of involvement.They examined the association between the presence of EIMs and demographic characteristics, diagnostic groups, sex, age groups, anatomical involvement, CD clinical types and fistula types. In addition, the patient groups and the relationship between EIM subgroups were evaluated. The study consisted of 393 patients with IBD, including 276 patients with UC and 117 with CD. The frequency of at least one EIM was 35.4% in 139 patients. When subgroups were examined,hepatosteatosis was the most common EIM, followed by hepatobiliary manifestations. EIM frequency was higher in CD than in UC when the two were compared. There was no significant relationship between EIM and diagnosis groups, anatomical location, clinical type of CD, or fistula types. Regarding the relationship between EIMs, there was no direct proportional relationship, but there was a significant decrease in the incidence of other EIMs in some EIMs. Determining the prevalence and risk factors associated with EIMs and raising awareness about this issue may aid in its early diagnosis and treatment. Thus, complications that may arise during the follow-up process can be avoided.

Impact of Vedolizumab on Extraintestinal Manifestations in Inflammatory Bowel Disease: Results From a Descriptive, Retrospective, Real-world Study.

Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, may develop extraintestinal manifestations (EIMs). The EMOTIVE study aimed to analyze the effect of vedolizumab on EIMs in a real-world cohort of patients with IBD. This multicenter, descriptive, retrospective study was conducted in Belgium, Denmark, Israel, the Netherlands, and Switzerland in adults with moderately to severely active IBD and concurrent active EIMs at vedolizumab initiation (index date), with a ≥6-month follow-up after the index date. The primary endpoint was resolution of all EIMs within 6 months of vedolizumab initiation. In 99 eligible patients, the most frequent EIMs were arthralgia (69.7%), peripheral spondyloarthritis (21.2%), and axial spondyloarthritis (10.1%). Within 6 and 12 months of vedolizumab initiation, 19.2% and 25.3% of patients reported resolution of all EIMs, while 36.5% and 49.5% of all EIMs were reported to be improved (combination of resolution and partial response), respectively. Vedolizumab treatment persistence at 12 months was 82.8%. Adverse events were reported in 18.2% of patients, with the most frequent being arthralgia (4.0%). This real-world study showed resolution of all EIMs in up to one-fourth of patients with IBD and improvement in up to half of EIMs within 12 months of vedolizumab treatment. Overall, vedolizumab was effective on EIMs in patients with IBD and showed a good safety profile.

ARTHRITIS AND ARTHRALGIA AS EXTRAINTESTINAL MANIFESTATIONS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE TREATED WITH VEDOLIZUMAB: A META-ANALYSIS

Abstract BACKGROUND Vedolizumab is a humanized gut selective drug that specifically targets α4β7 integrin and has been used successfully in the treatment of Inflammatory Bowel Disease (IBD). Although Vedolizumab is an effective treatment for IBD and acts specifically on the gastrointestinal system, some studies have reported extraintestinal manifestations as adverse events. One of the most frequently reported non-infectious adverse events is articular manifestations. However, it is difficult to know for sure whether the joint symptoms are due to the vedolizumab adverse event or due to extraintestinal symptoms of the disease itself. AIMS This systematic review and meta-analysis aimed to assess the incidence of extraintestinal manifestations in patients receiving Vedolizumab and to investigate whether these adverse events are indeed drug-related. METHODS Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of articular events in patients with Crohn’s Disease or Ulcerative Colitis who were treated with Vedolizumab. The considered outcomes were new-onset or worsening of pre-existing joint manifestations. We used Revman to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI). RESULTS The search strategy yielded 4.206 articles. After removal of duplicates and screening of results, 4 randomized studies met the inclusion criteria (Figure 1). A total of 2.466 patients with moderately to severe IBD were included. Of those, 1822 were randomized to intervention group, with Vedolizumab administration, and 644 to placebo. In the intervention group, 232 patients developed arthritis or arthralgia of any kind, versus 66 patients of placebo group (95% CI 0.7%-1.3%; Figure 2). Of those patients, 73,8% and 33% had prior treatment with anti-TNF and immunomodulators, respectively. 63% and 15% also had prior anti-TNF and immunomodulators previous failure, respectively. CONCLUSION The meta-analysis presented above shows a result without statistical significance to say that vedolizumab is responsible for the manifestations previously described. Therefore, it is necessary to hypothesize that the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, the body's response to the drugs or the exclusion of corticosteroids or anti-TNF from concomitant treatment with Vedolizumab. More studies with larger samples are needed, especially randomized clinical trials comparing Anti-TNF, corticosteroids and immunomodulators to assess the incidence of joint manifestations and even other rheumatologic manifestations in patients with Inflammatory Bowel Disease.

S933 Racial Disparities in Extraintestinal Manifestations in Patients With Inflammatory Bowel Disease

Introduction: Extraintestinal manifestations (EIM) are seen in 6% to 25% of IBD patients. While some EIMs occur as a direct result of bowel inflammation, other EIMs are due to an influx of mononuclear cells activated in the intestine but targeting extraintestinal organs. However, it is unclear if the pathogenesis and prevalence of EIM vary based on the race of IBD patients. Our study explored the prevalence of EIM of IBD among the major racial groups in the United States. Methods: We used a commercial database (Explorys Inc, Cleveland, OH) which includes electronic health record data from 26 major integrated US healthcare systems. Based on Systematized Nomenclature of Medicine – Clinical Terms (SNOMED-CT), we identified all patients (age >18 years) with a diagnosis of IBD between 1999 to 2022. Based on race, the study population was divided into two groups African American and Caucasian. The two groups were further categorized based on the extraintestinal manifestations of IBD. Results: Of the 70,383,890 individuals in the database, we identified 412,950 (0.59%) patients with IBD. Among all IBD patients, 32,870 were African American (8%) and 314,660 (76.2%) were Caucasian. When compared with Caucasians, African American IBD patients were at increased risk of pyoderma gangrenosum (OR 1.61), erythema nodosum (OR 1.39), pulmonary embolism (PE) (OR 1.06), deep vein thrombosis (DVT) (OR 1.24), interstitial lung disease (ILD) (OR 1.14), chronic kidney disease (CKD) (OR1.43), uveitis (OR 2.65), episcleritis (OR 1.78) and autoimmune hepatitis (AIH) (OR 1.54) . However, psoriasis (OR 0.49), vasculitis (OR 0.87) , ankylosing spondylitis (OR 0.82) and osteoporosis (OR 0.63) were less common in African American IBD patients (Table). Conclusion: Our large cohort of IBD patients demonstrates significant racial differences in the prevalence of EIM of IBD in the United States. The association between race and extraintestinal inflammation in IBD patients is unclear. Further research into racial variations in the pathophysiology of EIM in IBD patients is required. Table 1. - Comparison of The Prevalence of Extra-Intestinal Manifestations Among Caucasian and African-American IBD Patients AA IBD n=32,870 (%) Caucasian IBD n=314,660 (%) OR CI P-value Pyoderma Gangrenosum 210 (0.6%) 1,250 (0.4%) 1.61 1.61-1.87 < 0.0001 Erythema nodosum 180 (0.5%) 1,240 (0.4%) 1.39 1.19-1.63 < 0.0001 AIH 140 (0.4%) 870 (0.3%) 1.54 1.29-1.84 < 0.0001 ILD 1,080 (3.3%) 9,070 (2.9%) 1.14 1.07-1.22 < 0.0001 Episcleritis 80 (0.2%) 430 (0.1%) 1.78 1.40-2.26 < 0.0001 Uveitis 740 (2.3%) 2,710 (0.9%) 2.65 2.44-2.88 < 0.0001 PE 1,650 (5%) 14,930 (4.7%) 1.06 1.01-1.11 =0.0261 DVT 1,860 (5.7%) 14,500 (4.6%) 1.24 1.18-1.31 < 0.0001 CKD 4,740 (14.4%) 33,250 (10.6%) 1.43 1.38-1.47 < 0.0001 Psoriasis 440 (1.3%) 8,540 (2.7%) 0.49 0.44-0.54 < 0.0001 Vasculitis 1,930 (5.9%) 21,130 (6.7%) 0.87 0.83-0.91 < 0.0001 Ankylosing Spondylitis 250 (0.8%) 2,910 (0.9%) 0.82 0.72-0.93 = 0.0029 Osteoporosis 2,590 (7.9%) 37,680 (12%) 0.63 0.60-0.66 < 0.0001 Univariate analysis used to calculate OR, OR; odds ratio, CI; confidence interval, AA; African-American, IBD; inflammatory bowel disease, AIH;Autoimmune hepatitis, ILD; interstitial lung disease, PE; pulmonary embolism, DVT; deep venous thrombosis, CKD; chronic kidney disease.

S1024 Dermatologic Manifestations in Patients With Inflammatory Bowel Disease

Introduction: There are several extraintestinal manifestations of inflammatory bowel disease (IBD) including cutaneous. Furthermore, new biologics have been also associated with cutaneous side effects. However, the prevalence of extraintestinal manifestations in patients with IBD and those who receive anti-tumor necrosis factors (anti-TNFs) have not been extensively studied. Using a large database, we sought to describe the rates of selected cutaneous manifestations of IBD as long as adverse effects of anti-TNFs. Methods: We queried a multi-institutional database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 US healthcare systems was surveyed. A cohort of patients with a Systematized Nomenclature of Medicine-Clinical Terms of inflammatory bowel disease between 2017-2021 was identified. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS version 25, IBM Corp). For all analyses, a 2-sided P value of < 0.05 was considered statistically significant. Results: Of the 34,277,840 individuals in the database, 142,890 (0.42%) and 165,960 (0.48%) had a diagnosis of ulcerative colitis (UC) and Crohn’s disease (CD) respectively. Baseline characteristics of patients with IBD and control group are shown in Table 1. Compared to the non-IBD group, patients with a history of IBD had a higher rates of multiple skin conditions including erythema nodosum, pyoderma gangrenosum, sweet syndrome, psoriasis, lichen planus, alopecia, eczema, vitiligo, bullous disease, and skin cancers. Among IBD patients, those who are on anti-TNFs and immunomodulator (IM) had higher rates of herpes/zoster and candida infections, lichen planus, alopecia, eczema and melanoma and non-melanoma skin cancers compared to anti-TNFs alone (Table 3). Conclusion: In this large database, we found a higher risk association between IBD and multiple skin conditions including skin cancers. Interesting, IBD patients treated with anti-TNFs had double rates of melanoma and non-melanoma skin cancers. Further epidemiological studies are required to validate these findings and increase attention to adequately screening for skin cancers and dermatology referral while taking care of IBD.Figure 1

S2757 Eye-BD—A Rare Case of Orbital Myositis as an Extra-intestinal Manifestation of Crohn’s Disease

Introduction: Crohn’s Disease (CD) is often associated with a diverse array of extra-intestinal manifestations (EIMs). The estimated prevalence of EIMs in patients with CD is 25-70%. The estimated prevalence of ocular manifestations in patients with CD is 3.5-6.8%. Orbital myositis (OM), characterized by inflammation of the extraocular muscles, is a rare ocular EIM associated with CD. Case Description/Methods: A 22-year-old female with CD on ustekinumab for maintenance therapy in remission presented with three days of right eye swelling and pain with extraocular movements. CT of the orbits reported minimal pre-septal tissue swelling, without evidence of orbital cellulitis. She was started on NSAIDs. A week later, the patient presented to the Ophthalmology clinic with resolution of her right eye symptoms but with new, similar symptoms in her left eye, including diplopia, restriction of lateral and medial gaze, and chemosis of the lateral conjunctiva. She denied symptoms concerning for a Crohn’s flare or other EIMs. The initial CT of the orbits was reviewed, and an addendum was made, reporting subtle enlargements of multiple extra-ocular muscles in the right orbit. She was diagnosed with bilateral OM. Infectious, endocrine, and autoimmune work-up was performed which were unrevealing and her OM was likely an EIM of her CD. She was started on prednisone 40 mg daily, which resulted in complete resolution of her symptoms at one-week follow-up. She was kept on ustekinumab maintenance therapy as she remained in clinical remission without evidence of other EIMs and completed her steroid taper without further complication. The patient was informed of the high recurrence rate of CD-associated OM and close follow-up was arranged. (Figure) Discussion: Overall, our patient’s OM was a likely EIM of her CD, as further laboratory work-up for commonly implicated etiologies to include thyroid disease, vasculitides, sarcoidosis, and IgG4-related disease was all negative. This case illustrates a rare EIM of CD in a patient believed to be in clinical remission, emphasizing the point that certain EIMs may occur independently of gastrointestinal luminal disease activity. Given that a high index of suspicion was necessary to reach the diagnosis given the subtle exam and imaging findings, this case also reiterates the importance of timely diagnosis and early management to minimize morbidity risk, which can be best accomplished through multidisciplinary coordination among subspecialty providers.Figure 1.: Orbital CT, Coronal- Asymmetric enlargement of the medial rectus in the RT orbit.

The impact of biologic therapies on extra-intestinal manifestations in inflammatory bowel disease: A multicenter study.

IntroductionPatients with inflammatory bowel disease (IBD) have a high risk of developing extra-intestinal manifestations (EIMs). We aimed to assess the cumulative incidence and clinical course of EIMs in patients treated with Vedolizumab (VDZ) and non-gut selective biologic drugs.Materials and methodsIn this multicenter observational study, we enrolled 1,182 patients with IBD under biologic treatment in tertiary care centers, collecting the rate of new-onset EIMs and the clinical course of new and pre-existing EIMs since the introduction of the ongoing biologic drug (259 VDZ vs. 923 non-gut selective agents, median time 3 vs. 4 years).ResultsAmong 1,182 patients with IBD (median age of 46 years; 55% men) on biologics, the overall cumulative incidence of new onset EIMs was 4.1% (49/1,182), in particular 6.6% (17/259) on VDZ vs. 3.5% (32/923) on non-gut selective biologics (p = 0.02). Among 224 patients reporting new or pre-existing EIMs, those on VDZ showed a higher rate of clinical worsening compared with non-gut selective therapies (15.5 vs. 7.3%, p = 0.08). However, both showed a similar rate of modification of the therapeutic regimen. Female gender [hazard ratio (HR) 2.18], a longer course of ongoing biologic therapy (HR 1.18), ulcerative colitis (UC) (HR 1.83), and VDZ therapy (HR 1.85) were significant risk factors for developing new EIMs.DiscussionOur study suggests that the type of biologic treatment might affect the risk of developing EIMs, with a slightly higher risk in patients on gut-selective therapies. However, a similar clinical course is observed in the two groups.

HIF1α-Dependent Induction of TFRC by a Combination of Intestinal Inflammation and Systemic Iron Deficiency in Inflammatory Bowel Disease.

Background and Aims: Iron deficiency (ID) is a frequent extra-intestinal manifestation in patients with Inflammatory Bowel Disease (IBD), who often do not respond to iron supplementation. Iron is a cofactor for hydroxylases that suppress the hypoxia-inducible factor-1α (HIF1α), a transcription factor regulating iron homeostasis. We hypothesized that iron deficiency affects mucosal HIF1α activity in IBD. Methods: IBD patients (n = 101) were subdivided based on iron status (ferritin levels or transferrin saturation) and systemic inflammation (C-reactive protein levels). 154 corresponding ileal and colonic biopsies were analyzed for differential expression of 20 HIF1α pathway-associated genes and related to iron and inflammation status. In vitro expression of selected HIF1α pathway genes were analyzed in wild-type and HIF1A-null Caco-2 cells. Results: Gene expression of the mucosal HIF1α pathway was most affected by intestinal location and inflammatory status. Especially, ileal mucosal TFRC expression, encoding the transferrin receptor TFR1, was increased in inflamed tissue (p < 0.001), and further enhanced in ID. Accordingly, TFRC expression in inflamed tissue associated negatively with serum iron levels, which was not observed in the non-inflamed mucosa. The HIF1α pathway agonist DMOG increased TFRC expression in Caco-2 cells, which was blunted in HIF1A-null cells. Conclusion: We demonstrate that inflammation and anatomical location primarily determine HIF1α pathway activation and downstream TFRC expression in the intestinal mucosa. IBD patients with ID may benefit from treatment with HIF1α-agonists by 1) increasing TFRC-mediated iron absorption in non-inflamed tissue and 2) decreasing mucosal inflammation, thereby improving their responsiveness to oral iron supplementation.

Bone Alterations in Inflammatory Bowel Diseases: Role of Osteoprotegerin.

Metabolic bone disorders are one of the most frequent extra-intestinal manifestations in patients with inflammatory bowel diseases (IBD) that might result in an increase of skeletal fragility and risk of fracture. These disorders are a consequence of bone–gut crosstalk alterations, particularly due to inflammation, which involves the RANK-RANKL-Osteoprotegerin (OPG) pathway. This cross-sectional study investigates the role of serum OPG on bone health in IBD patients. In all patients, we carried out BMD measurements at the lumbar spine and femoral neck by the dual-energy X-ray absorptiometry (DXA), and evaluation of serum OPG, 25(OH)D, and PTH. We also divided all IBD patients into two groups: group 1 consisted of premenopausal women and men younger than 50 years old, while group 2 included postmenopausal women and men aged more than 50 years old. We enrolled 36 UC patients (51%), 34 CD patients (49%), and 70 healthy controls. IBD group mean age was 44 ± 17.3 years old, with a mean disease duration of 6 years. IBD patients had a mean value of OPG of 48.1 ± 26.64 pg/mL, while mean OPG in the control group was 61.35 ± 47.19 pg/mL (p < 0.05). In group 1, there was a correlation between BMD Z-scores at the lumbar spine and femoral neck and mean OPG levels in UC subjects (r = 0.47 and r = −0.21, respectively; p < 0.05), and only between Z-score at the lumbar spine and OPG level in the CD group (r = 0.83, p < 0.05). For the patients of group 2, we report a statistically significant correlation between T-score measured at the lumbar site in both UC and CD patients (r = −0.79 and r = 0.77, respectively; p < 0.05). In our study, we demonstrated serum OPG levels to be significantly decreased in IBD subjects compared to healthy age-matched individuals. However, according to our data, it seems that the measurement of serum OPG levels is not useful to better define metabolic bone disorders in IBD patients.

Extraintestinal manifestation of inflammatory bowel disease and associated factors in pediatric patients

ObjectiveExtraintestinal manifestations in irritable bowel disease (IBD), Crohn's disease and ulcerative colitis are reported in different system of the body. We aimed to investigate the factors determining disease severity and evaluate extraintestinal manifestations in patients with irritable bowel disease based on disease activity scoring system. MethodsThis cross-sectional study was conducted on all patients with irritable bowel disease referred to clinic and gastroenterology ward of (XXX). Medical history, gastrointestinal complications and incidence of extraintestinal manifestations were recorded. Disease severity in ulcerative colitis was rated based on PUCAI (Pediatric Ulcerative Colitis Activity Index) score and in Crohn's disease was calculated based on PCDAI (Pediatric Crohn's Disease Activity Index) score. ResultsOf 73 children included in our study, 54.80% were diagnosed with ulcerative colitis and 45.20% were diagnosed with Crohn's disease. The most prevalent symptom was weight loss (81.81%), diarrhea (72.72%) and abdominal pain (69.69%) in Crohn's diseases and bloody diarrhea (80%), abdominal pain (77.5%) and weight loss (57.5%) in ulcerative colitis. The average of PCDAI score was 43.44 and PUCAI score was 35.62. The most prevalent extraintestinal manifestation of the disease was arthritis in 7 Crohn's disease patients (21.21%) and 5 patients (12.5%) with ulcerative colitis, oral plague in 5 patients (15.15%) with Crohn's disease and erythema nodosum in 2 patients (6.06%) with Crohn's disease. ConclusionThe severity of oral plaque was positively associated with the severity of the disease. There was no significant association among other parameters. Scoring systems, to determine the extraintestinal manifestation, should be standardized based on the scoring outcomes.

OP33 Effect of upadacitinib (UPA) treatment on extraintestinal manifestations (EIMs) in patients with moderate-to-severe Ulcerative Colitis (UC): Results from the UPA Phase 3 programme

Abstract Background EIMs are common in patients with UC and are associated with impaired quality of life. This analysis evaluated the impact of treatment with the selective Janus kinase 1 inhibitor UPA on EIMs in patients with moderate-to-severe UC. Methods Data were included from two induction studies (U-ACHIEVE Induction [NCT02819635] and U-ACCOMPLISH [NCT03653026]) and a maintenance study (U-ACHIEVE Maintenance). Patients with moderate-to-severe UC were randomised 2:1 to 8 weeks’ induction treatment with UPA 45 mg once daily (QD) or placebo. Patients with a clinical response to induction were re-randomised (1:1:1) to 52 weeks’ maintenance treatment with UPA 15 mg or 30 mg QD, or placebo. The presence of EIMs (peripheral arthropathy, axial arthropathy, episcleritis, uveitis, iritis, erythema nodosum, pyoderma gangrenosum, Sweet’s syndrome, oral aphthous ulcers, primary sclerosing cholangitis, autoimmune hepatitis, venous thromboembolism, chronic obstructive pulmonary disease, bronchiectasis, nephrolithiasis and anaemia) was captured in the EIM form at the start of induction (baseline) and at every visit up to Week 52. The induction study results were pooled for analysis. Results At baseline, 25.0% and 26.5% of patients in the UPA 45 mg QD and placebo induction groups had ≥1 EIM, while 24.3%, 26.6% and 24.8% of patients randomised to maintenance treatment with UPA 15 mg QD, UPA 30 mg QD or placebo, respectively, had ≥1 EIM (Table 1). The most common EIMs at baseline were anaemia, peripheral arthropathy and axial arthropathy; all other EIMs were reported in &amp;lt;2% of patients (Table 1). The proportion of patients reporting resolution of any EIM, arthropathy (peripheral and axial) and anaemia at Week 8 was numerically greater with UPA 45 mg QD than placebo in the induction studies (Figure 1A). Resolution at Week 52 of any EIM in patients with ≥1 EIM at baseline was significantly increased with UPA 30 mg QD (p&amp;lt;0.001), and numerically greater with UPA 15 mg QD, versus placebo (Figure 1B). In patients with arthropathy (peripheral or axial) at baseline, the proportion achieving resolution of arthropathy (peripheral and axial) at Week 52 was significantly increased with UPA 30 mg QD (p=0.010), and numerically higher with UPA 15 mg QD, versus placebo (Figure 1B). The same was true of anaemia resolution in patients with anaemia at baseline (p=0.019 for UPA 30 mg QD versus placebo; Figure 1B). Conclusion UPA treatment is effective in resolving EIMs in patients with UC. EIM symptom resolution was improved versus placebo following induction treatment with UPA 45 mg and after maintenance treatment with UPA 15 or 30 mg, with the 30 mg dose providing statistically significant improvements versus placebo.

Alterations in Fecal Microbiota in Patients with Inflammatory Bowel Disease and Enteropathic Arthropathy

Objectives: Inflammatory arthritis or enteropathic arthropathy (EA) is a common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD). We aimed to determine whether EA in patients with IBD was associated with changes in the gut microbiome. Methods: Consecutive patients with ulcerative colitis (UC) or Crohn's disease (CD) were prospectively recruited and characterized. Stool samples were collected and real-time polymerase chain reaction targeting 16S ribosomal RNA genes was used to quantitate specific communities of “beneficial”; (Clostridium coccoides, bifidobacteria, and lactobacilli) or “aggressive” (Bacteroides and Enterobacteriaceae) bacterial flora. In 12 patients with UC and 12 with CD, fecal 16S ribosomal RNA gene was subjected to next-generation sequencing (NGS) and bacterial taxa were enumerated and compared between IBD patients with and without EA. Results: Sixty-eight patients with UC and 60 with CD were included in the study. Arthropathy was noted in 13 (21.6%) patients with CD and 11 (16.1%) patients with UC. Arthritis was peripheral in 12, axial in 7, and mixed in the rest. The most prevalent commensal bacteria in IBD patients were Bacteroides and Bifidobacterium. Enterobacteriaceae count was significantly higher in patients with UC than in CD. UC patients with EA had relatively higher Enterobacteriaceae and lesser C. coccoides than UC patients without EA. The NGS analyses showed a significant reduction in alpha diversity in patients with EA compared to IBD without EA. Patients with EA had significantly greater abundance of enterococci compared to IBD without EA. Conclusions: EA in IBD patients is characterized by gut microbiome changes including dysbiosis, reduction in alpha diversity, and increased abundance of enterococci.

P628 Risk Factors Associated with Extraintestinal Manifestations in Patients with Inflammatory Bowel Diseases

Abstract Background Risk factors associated with extraintestinal manifestations (EIMs) in patients with inflammatory bowel disease (IBD) have been evaluated mainly in retrospective studies. We aimed to determine risk factors associated with EIMs and to compare the frequency of EIMs between ulcerative colitis (UC) and Crohn’s disease (CD), based on retrospectively-prospectively collected data of a cohort of IBD patients followed in daily clinical practice. Methods Patients with biopsy-confirmed IBD aged 10–80 years old were included in the study. A comprehensive questionnaire was used to collect data on each site visit from July 2018 until March 2020. Logistic regression analysis and multivariable-adjusted models were used to examine risk factors associated with EIMs and chi-squared test was used to compare the frequency of EIMs between patients with UC and CD. Results 300 patients with IBD (180 with CD, 113 with UC, and 7 with indeterminate colitis) were evaluated. EIMs were observed in 49% of patients, with a 2-fold increased risk in CD (OR 2.31; 95% CI:1.37–3.89; P&amp;lt;.005). The musculoskeletal system was affected in 38% (43% in CD vs 29% in UC, OR 1.86; 95% CI:1.08–3.20; P&amp;lt;.05) with peripheral arthropathy being the most common manifestation (33% in CD vs 23% in UC, P=.095), followed by dermatological manifestations (13%), with a 4-fold increased risk of erythema nodosum in CD (11% vs 3% in UC, OR 3.95; 95% CI:1.12–13.93; P&amp;lt;.05). On univariate logistic regression analysis history of hospitalization for IBD, history of surgery for IBD, aphthous stomatitis, perianal disease, thyroiditis Hashimoto, age, use of thiopurines, and/or anti-TNF in the past were associated with increased risk of developing EIMs. A trend for increased risk of EIMs was found for family history of IBD in first-degree relatives (OR 2.47; 95% CI:0.91–6.74; P=.078) and fecal calprotectin above 250 μg/g (OR 2.22; 95% CI:0.90–5.47; P&amp;lt;.084). On multivariate analysis only aphthous stomatitis (OR 4.60; 95% CI:2.32–9.13; P&amp;lt;.001), perianal disease (OR 2.30; 95% CI:1.17–4.50; P&amp;lt;.05), thyroiditis Hashimoto (OR 2.82; 95% CI:1.03–7.74; P&amp;lt;.05) and age (2% increase in risk per year, OR 1.02; 95% CI:1.01–1.03; P&amp;lt;.05) were significant for EIMs. Conclusion In this retrospective/prospective study 49% of IBD patients developed EIMs with a 2-fold increased risk in CD. Musculoskeletal and dermatological manifestations were the most frequent EIMs. Aphthous stomatitis, perianal disease, thyroiditis Hashimoto and age were associated with increased risk of EIMs.

P406 A retrospective analysis of the efficacy of vedolizumab on extra-intestinal manifestations in patients with inflammatory bowel disease across five European countries

Abstract Background Vedolizumab is an α4β7 integrin monoclonal antibody indicated for moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC). There are limited data on how vedolizumab impacts extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD). The aim of the study was to analyse the effect of vedolizumab on EIM in a real-world cohort of IBD patients. Methods A multicentre retrospective study was conducted in Belgium, Denmark, Israel, the Netherlands and Switzerland. Adult patients with moderately to severely active IBD and concurrent active EIM with at least 6 months follow-up after vedolizumab initiation (index date) were enrolled. Improvement of EIM was defined as absence of symptoms (resolution) or partial response (reduction of symptoms). Results 99 patients were included (UC: 44, CD: 55); the majority of active EIM at index were musculoskeletal (Table 1). Median disease duration at index was 9 (IQR: 3-19) years and 77% of patients had been exposed to 1+ biologic. Overall, after 6 and 12 months of vedolizumab, 37% and 50% of EIM respectively were reported as improved, 22%, 25% as stable (no change) and 1% and 3% as worsened (Table 2), missing values were 5% and 4%, respectively. Median time since first EIM improvement was 0.5 months (Figure 1). At 6 and 12 months, 48% (10/21) and 33% (6/18) of patients experienced clinical response/remission of their IBD, respectively. Vedolizumab treatment persistence at 12 months was 83% overall (Figure 2). Adverse Events were reported for 18% patients; 96% of them non-serious. Conclusion Vedolizumab treatment was associated with an improvement in 37% and 50% of EIM at 6 and 12 months, respectively, in a real-world IBD cohort.

Extraintestinal manifestations at baseline, and the effect of tofacitinib, in patients with moderate to severe ulcerative colitis.

Introduction:Extraintestinal manifestations (EIMs) in patients with ulcerative colitis (UC) are common. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. We evaluated the efficacy of tofacitinib in patients with EIMs, and the impact of tofacitinib on EIMs in patients with UC in the OCTAVE clinical program.Methods:Data from two 8-week induction studies (OCTAVE Induction 1 and 2) and a 52-week maintenance study (OCTAVE Sustain) were analyzed. The effect of tofacitinib on efficacy outcomes stratified by EIM status, proportion of predefined prior and active EIMs at baseline, and change from baseline in EIMs were determined at the end of the treatment period (weeks 8 or 52), or at early termination.Results:At baseline of OCTAVE Induction 1 and 2, and OCTAVE Sustain, 27.0% and 9.0% of patients had a history of EIMs (prior or active), respectively. Patients treated with tofacitinib 10 mg twice daily (BID) achieved remission and had endoscopic improvement in all studies, irrespective of any history of EIMs. A greater proportion of patients had active peripheral arthritis at baseline of OCTAVE Induction 1 and 2 versus OCTAVE Sustain. In OCTAVE Induction 1 and 2, similar proportions of tofacitinib and placebo-treated patients with active peripheral arthritis experienced either no change (81.3% and 85.7%, respectively) or an improvement (15.6% and 14.3%, respectively). By week 52 of OCTAVE Sustain, improvements in active peripheral arthritis were only observed in tofacitinib-treated patients (16.7% and 33.3% with tofacitinib 5 and 10 mg BID, respectively).Conclusion:Any history of EIMs did not influence the efficacy of tofacitinib 10 mg BID for induction or maintenance of UC. The most common active EIM was peripheral arthritis, for which many patients in OCTAVE Induction 1 and 2, and OCTAVE Sustain, reported improvement or no change from baseline with tofacitinib treatment.Clinicaltrials.gov:NCT01465763; NCT01458951; NCT01458574