Severe Disease Activity Research Articles

E008 Review of rheumatology care for women of childbearing age

Abstract Background/Aims Autoimmune rheumatic diseases are frequently diagnosed in women of childbearing age. Managing these conditions during pregnancy is complex because commonly used disease-modifying antirheumatic drugs (DMARDs) can pose risks. Specialized care for this patient group is crucial, necessitating adherence to established rheumatology practice standards and British Society for Rheumatology (BSR) guidelines. Our main objective is to review management of childbearing age females with rheumatic diseases attending Basildon hospital as per BSR guidelines. Methods The data for this retrospective study was collected from the electronic records of female patients attending the rheumatology outpatient clinic at Basildon Hospital between September and December 2022. We reviewed age, the specific rheumatological diagnosis, disease duration, disease activity, current medications, and whether general advice or pregnancy-specific advice was provided. Results Out of the initial cohort of 63 female patients, 48 (76%) aged between 18-55 years were selected as women of childbearing age, The median age was 46 years, with 65% in the age groups of 31-50 years, 25% in group 51-55 years and 10% 18-30 years age group. 58% of patients had inflammatory arthritis, 18.7% had connective tissue disease, 18.7% had other conditions such as hypermobility, osteoarthritis, and regional pain syndrome, 2.3% were diagnosed with vasculitis and 2.3% with polymyalgia rheumatica. Breakdown of inflammatory arthritis patients revealed rheumatoid arthritis in 64%, psoriatic arthritis 15% and ankylosing spondylitis 12%. Axial spondyloarthropathy, palindromic rheumatism, and juvenile idiopathic arthritis, each accounted for 3%. Regarding prescribed medications, 66% of the individuals were on conventional DMARDs, biologics 24%, corticosteroids 6% and 4% were on other treatments. The DMARDs prescribed were methotrexate 27%, hydroxychloroquine 19%, sulfasalazine 13%, mycophenolate 3% and leflunomide 1%. The majority of patients had disease activity in remission or mild, each accounting for 23%. Moderate and severe disease activity were reported in 21% each of the audited sample. Patients received advice specifically related to pregnancy 29%, while 71% did not have documented pregnancy-related guidance. 70% of females of reproductive age received general advice. Conclusion The study highlights a gap in pregnancy-related advice among the childbearing age patients as only 29% received guidance on pregnancy. This underpins the need for proactive counselling and education for female patients in routine practice, work in partnership with obstetric teams, and primary care to reduce potential pregnancy related complications and improve outcomes. Disclosure M. Mohareb: None. S. Ahmed: None. A. Bharadwaj: None. A. Nandagudi: None.

Albumin to globulin ratio (AGR) in systemic lupus erythematosus: correlation with disease activity.

To investigate the role of albumin-to-globulin ratio (AGR) in systemic lupus erythematosus (SLE) and its relationship with disease activity. This retrospective study consecutively selected patients with SLE and healthy controls. Patients were divided into three groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K): group 1 (mild disease activity, SLEDAI-2K ≤ 6), group 2 (moderate disease activity, SLEDAI-2K 7-12) and group 3 (severe disease activity, SLEDAI-2K > 12). Predictors of SLE disease activity were analysed by ordinal logistical regression. A total of 101 Chinese patients with SLE and 75 healthy Chinese controls were included. Patients with SLE had lower AGR values than healthy individuals, and group 3 patients with SLE displayed lower AGR values than those in group 1, but similar values to group 2. AGR was inversely correlated with SLEDAI-2K (r = -0.543). Ordinal logistic regression analysis showed that lower AGR (β = -1.319) and lower complement C4 (β = -1.073) were independent risk factors for SLE disease activity. AGR was decreased in patients with SLE and may be utilized as a useful inflammatory biomarker for monitoring SLE disease activity.

When should the use of biological agents be considered in persistent oligoarticular juvenile idiopathic arthritis patients?

JADAS10 indicating ongoing severe disease activity at 3rd and 6th months rather than baseline JADAS10 is associated with the addition of bDMARDs. • Oligoarticular JIA patients have the best outcomes among JIA categories and respond favorably to first-line therapies such as non-steroidal anti-inflammatory drugs and intraarticular corticosteroid injections. • Clinically inactive disease rates have increased with the widespread use of biological agents in oligoarticular JIA patients who have not responded to initial therapies. • Approximately one-fifth of patients with persistent oligoarticular JIA on methotrexate may require the addition of a biological disease modifying anti-rheumatic drug during follow-up. • The JADAS10 calculated at 3 and 6months is a valuable tool to identify patients who should be added biological disease modifying anti-rheumatic drugs in persistent oligoarticular JIA.

Assessment of central nervous system vasculitis in children based on high-resolution vascular wall imaging.

Central nervous system vasculitis (CNSV) is a rare disease. High-resolution vessel wall imaging (HR-VWI) enables the identification of inflammatory changes within the vessel wall. Few studies have applied HR-VWI to assess CNSV in children. This study delves into the utility of HR-VWI for diagnosing and treating CNSV in children, with the aim of enhancing clinical diagnosis and efficacy evaluation. Imaging data were acquired from children who underwent HR-VWI examinations. The study meticulously analysed clinical data and laboratory tests to discern the characteristics and distribution patterns of diverse vasculitis forms. In children, CNSV mainly involves medium vessels with grade 1 and 2 stenosis (grade 4 stenosis is rare), and the imaging features generally show centripetal and moderate enhancement, suggesting that this feature is specific for the diagnosis of CNSV. High-grade stenosis, concentric enhancement and strong enhancement of the vasculature indicate more severe disease activity. Remarkably, HR-VWI proved to be significantly more sensitive than magnetic resonance angiography in detecting CNSV. Among the 13 cases subjected to imaging review, 8 demonstrated a reduction or resolution of vessel wall inflammation. In contrast, five patients exhibited worsening inflammation in the vessel wall. HR-VWI demonstrated that changes in vessel wall inflammation were closely correlated with changes in brain parenchymal lesions and symptoms. This study underscores the diagnostic value of HR-VWI in CNSV assessment and treatment monitoring, offering a quantitative evaluation of CNSV in children.

Treatment outcome and survival status among adult patients treated for lupus nephritis in selected tertiary hospitals of Ethiopia

Lupus nephritis (LN) is kidney involvement of systematic lupus erythematous that ranges from mild to severe and occurs in 60% of adult patients. Despite advances in therapy, LN morbidity and mortality remains high. There is a paucity of data regarding adult LN patient's treatment outcome, survival status, and associated factors in developing countries, particularly in Ethiopia. This study aimed to assess the treatment outcome, survival status, and associated factors of adult patients treated for LN in two selected tertiary hospitals [Tikur Anbessa Specialized Hospital (TASH) and St. Paul’s Hospital Millennium Medical College (SPHMMC)] of Addis Ababa, Ethiopia. A hospital-based retrospective cross-sectional multicenter study was conducted from January 1, 2016 to January 1, 2021. Socio-demographic, clinical, and treatment-related data were collected from patient’s medical records by using a structured abstraction checklist. Descriptive statistics were used to summarize the quantitative data as appropriate. The modified Aspreva Lupus Management Study (mALMS) criteria was applied to categorize LN treatment outcomes into complete, partial, and non-response. Multinomial logistic regression analysis was performed to identify predictors of LN treatment outcome. Patients’ survival was estimated by using Kaplan–Meier and Cox proportion regression analysis. P value < 0.05 was considered to declare statistical significance. A total of 200 LN patients were included in the final analysis. Amongst these, the majority of them (91.5%) were females. The median age of the patients was 28 (15–60) years. The mean duration of treatment follow-up was 28 months. The commonly prescribed immunosuppressive drugs during both the induction (49.5%) and maintenance (60%) phases were a combination of mycophenolate mofetil with prednisolone. Complete, partial, and non-responses at the last follow-up visit accounted for 66.5%, 18.0%, and 15.5%, respectively. Patient survival at the last follow-up visit was more than 90% for patients with complete response to the induction therapy. Non-response at the last follow-up visit was significantly associated with severe disease activity index (adjusted odds ratio [AOR] = 6.25, 95% confidence interval [CI] 1.49–26.10), presence of comorbidity (AOR = 0.21, 95% CI 0.05–0.92), baseline leucopenia (AOR = 14.2, 95% CI 1.04–201.3), partial response at the end of induction therapy (AOR = 32.63, 95% CI 1.4–736.0), and duration of induction therapy of greater than 6 months (AOR = 19.47, 95% CI 1.5–258.8). This study unveiled that lower numbers of LN patients were presented with non-response at the last follow-up visit and non-response to induction therapy was associated with lower patients’ survival rates compared with complete or partial response.

A230 SARCOPENIA IN PRIMARY SCLEROSING CHOLANGITIS AND INFLAMMATORY BOWEL DISEASE IN PAEDIATRICS AND CLINICAL IMPLICATIONS

Abstract Background Sarcopenia is defined in paediatrics as a decrease in muscle mass for a given age. The coexistence of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) is recognized to be a distinct entity with a distinct phenotype. However, to date, there is no study that has assessed the prevalence of sarcopenia and its clinical implications in paediatric PSC-IBD, compared to paediatric colitis. Aims We first aimed to determine whether sarcopenia is more prevalent in paediatric PSC-IBD than children with colitis without liver disease. Our secondary aim was to explore the prognostic implications of sarcopenia in paediatric PSC-IBD both for liver and IBD outcomes. Methods This was a single-center retrospective cohort study including paediatric IBD patients with and without PSC who underwent magnetic resonance enterography (MRE) for clinical care. Psoas muscle area (PMA) at the L4-5 intervertebral disc level was calculated. Sarcopenia was defined as PMA ampersand:003C 3rd percentile for age and sex. The association between PSC and sarcopenia was examined using logistic regression, adjusting for variables selected using change in estimate method. Survival analysis was used to examine the association between sarcopenia and IBD/liver outcomes. Results A total of 85 IBD patients were included – 31 PSC-IBD and 54 colitis controls. Both groups had male predominance. A higher proportion of children with PSC-IBD had pancolitis (Pampersand:003C0.001), and PSC-IBD patients had less severe clinical IBD disease activity than controls (P=0.003). Sarcopenia was present in 39% PSC-IBD and 18% colitis (odds ratio (OR) 2.7, 95%CI 1.02-7.53, P=0.044). Adjusting for endoscopic Mayo score and biologic therapy exposure prior to MRE, the adjusted OR for the association between PSC and sarcopenia was 4.22, 95%CI 1.32-13.44, P=0.015. Sarcopenic patients were younger than non-sarcopenic patients (mean 12.4(SD2.9) years versus 14.3(SD2.3) years, P=0.003), and also had lower weight and height (Pampersand:003C0.001, P=0.002, respectively). Sarcopenia was not a risk factor for escalation to biologics and/or surgery (hazards ratio (HR) 1.18, 95%CI 0.55-2.50, P=0.67) nor for progression to liver fibrosis and/or portal hypertension (HR 0.40, 95%CI 0.044-3.54, P=0.40). Conclusions Sarcopenia was 4 times more frequent in PSC-IBD compared to colitis controls in our cohort, after accounting for differences in IBD severity and biologic exposure. Sarcopenia may represent an additional feature that is distinct to PSC-IBD versus colitis without associated PSC. Funding Agencies None

The Concordance of Patient-Reported Symptoms, Physical Examination and Ultrasound-Detected Synovitis, in Active Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint synovitis and systemic inflammation, with joint swelling and tenderness as common clinical manifestations. Accurate assessment of disease activity is crucial for effective management and treatment planning. While ultrasound (US) has emerged as a sensitive tool for detecting synovitis, its concordance with clinical examination findings remains a subject of ongoing research. Objective: The objective of this study was to evaluate the concordance between clinical examination findings and ultrasound-detected synovitis in RA patients, with an emphasis on the diagnostic value of joint swelling and tenderness. Methods: This observational, cross-sectional study involved 40 RA patients with moderate to severe disease activity, assessed at a single center. Following ethical approval and informed consent, patients were evaluated for joint swelling, tenderness, and patient-reported symptoms. Ultrasound examinations were conducted to detect synovitis, employing gray scale (GS) and power Doppler (PD) modalities. Concordance between clinical findings and US-detected synovitis was analyzed using Cohen's kappa statistic. Disease activity was categorized using the DAS28 score, with subgroup analyses across different disease activity states. Results: Joint swelling demonstrated the highest concordance with US-detected synovitis (kappa = 0.44), while joint tenderness showed lower concordance (kappa = 0.23). Analysis across disease activity states revealed consistent concordance for joint swelling (kappa values ranging from 0.38 to 0.41), regardless of disease severity. Patient-reported symptoms and the use of specific treatments (methotrexate and biologics) were also analyzed, with 90% of patients on methotrexate and 10% on biologics. The study population was predominantly female (86%) and middle-aged (20 to 40 years: 66%). Conclusion: Our findings indicate that joint swelling is a more reliable clinical indicator of synovitis in RA patients compared to joint tenderness. This suggests that disease activity scoring systems in RA might benefit from placing greater emphasis on swelling and patient-reported symptoms. Future research should explore the integration of these parameters to enhance the accuracy and efficiency of RA management.

Single-Cell Profiling of Bone Marrow B Cells and Early B Cell Developmental Disorders Associated With Systemic Lupus Erythematosus.

The peripheral B cell compartment is heavily disturbed in systemic lupus erythematosus (SLE), but whether B cells develop aberrantly in the bone marrow (BM) is largely unknown. We performed single-cell RNA/B cell receptor (BCR) sequencing and immune profiling of BM B cells and classified patients with SLE into two groups: early B cell (Pro-B and Pre-B) normal (EBnor) and EB defective/low (EBlo) groups. The SLE-EBlo group exhibited more severe disease activity and proinflammatory status, overaction of type I interferon signaling and metabolic pathways within the B cell compartment, and aberrant BCR repertoires compared with the SLE-EBnor group. Moreover, in one patient with SLE who was initially classified in the SLE-EBlo group, early B cell deficiency and associated abnormalities were largely rectified in a second BM sample at the remission phase. In summary, this study suggests that early B cell loss in BM defines a unique pathological state in a subset of patients with SLE that may play an active role in the dysregulated autoimmune responses.

CLINICAL, BIOCHEMICAL, AND INTESTINAL ULTRASONOGRAPHY RESPONSE TO CURCUMIN-QINGDAI (CURQD) COMBINATION IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A CASE SERIES

Abstract BACKGROUND There are few FDA-approved therapies for pediatric patients with inflammatory bowel disease (IBD). Clinical remission rates plateau at 60%, even with the currently available biologic therapies. Nutraceuticals are novel alternative treatments that can be used as adjunct treatments. AIM In this case series of 8 patients, we aim to present the clinical and radiological response to a novel nutraceutical agent, CurQD, composed of QingDai (Indigo Naturalis) and Curcumin. METHODS Patients included required a baseline pre-treatment clinical assessment and at least a single follow-up examination. Clinical status was evaluated based on the Physician General Assessment (PGA, determined independently from the clinical scoring systems) and the pediatric Crohn’s disease activity index (PCDAI) or the pediatric ulcerative colitis activity index (PUCAI), as appropriate. Baseline biomarkers (Hgb, ESR, CRP, albumin, and calprotectin(FC)) were collected pre and post-treatment when available. When available, intestinal ultrasound (IUS) features were also noted. On the IUS, bowel wall thickness (BWT, in mm) and color Doppler signaling (measured by the modified Limberg score graded 0,1,2, or 3 based on severity) were collected. The longitudinal changes were demonstrated on the most inflamed segment. Considering the small sample size, only descriptive statistics were applied. RESULTS Primary therapies received included anti-TNFα for 3 patients, ustekinumab in 3 patients, 1 on vedolizumab, and mesalamine in 1. Baseline assessment was done at a median time of 1.8 weeks (IQR 0.9-3.6 weeks) before starting the supplement, and the follow-up was 3.9 weeks (IQR 2.8-5.4 weeks) after starting the supplement. Two patients were in clinical remission at baseline but had active disease based on Doppler activity on IUS, 3 patients had mild active disease, and 3 patients had either moderate or severe disease activity. At follow-up, all patients but one were in clinical remission. (Table 1) Median baseline FC decreased from 1047.4 ug/g (IQR 532.4-1107) to 27.1 (IQR 27.5-341.3). Five patients had complete IUS information. When isolating the most inflamed segment on IUS, all patients demonstrated a response to treatment, noted by a decrease in BWT and/or a decrease in Doppler signaling. (Figure 1) No patient had a baseline therapy change after their follow-up. One patient reported abdominal bloating after starting CurQD and discontinued the product after five weeks. CONCLUSION CurQD is a promising nutraceutical that may assist in breaking the therapeutic ceiling of biological therapies in IBD. Based on this small experience, a larger randomized controlled trial in children would be needed to assess the safety and efficacy of this product in this vulnerable patient group. Furthermore, IUS is a practical tool for evaluating response to therapy in a pragmatic clinical setting. Table 1 Change in clinical disease scores in patients receiving CurQD Figure 1 Description of changes in a) bowel wall thickness (BWT) and b) color Doppler signaling (measured by the modified Limberg score) in patients treated with CurQD.

P422 Prevalence of poor sleep quality assessed by wrist actigraphy and sleep questionnaire in Inflammatory Bowel Disease patients and its association with disease activity and quality of life

Abstract Background An association between active inflammatory bowel disease (IBD) and poor sleep quality has been proposed, however studies evaluating both subjective and objective assessment of disease activity and sleep quality are limited. Our study aimed to investigate the prevalence of poor sleep quality assessed by wrist actigraphy and sleep questionnaires in IBD patients and its association with disease activity and quality of life. Methods A prospective observational study was conducted in Siriraj Hospital, Mahidol University, Bangkok, Thailand from March 2021 to December 2022. Eligible IBD patients were categorized into remission, mild, and moderate-to-severe groups, based on standard clinical disease activity scores. Demographic data, inflammatory markers, inflammatory bowel disease questionnaire (IBDQ), sleep questionnaire (Pittsburgh Sleep Quality Index, PSQI), and seven-day sleep data from wrist actigraphy (Actiwatch®, CamNtech, Cambridge, United Kingdom) were obtained. The prevalence of sleep disorder and group comparison were analyzed. Results Eighty-four participants (40 Crohn’s disease, 44 UC), consisting of 60 remission, 16 mild, and 8 moderate-to-severe disease activity, were enrolled. Baseline demographic data were comparable between each group. Lower hemoglobin and albumin levels, and higher serum C-reactive protein, and fecal calprotectin levels were found in the more clinically active groups (table1). Fifty patients (60%) had poor sleep defined by PSQI &amp;gt; 5 with a trend to be higher in the group with active symptoms (57% in remission, 63% in mild, and 75% in moderate-to-severe group, p=0.31). Using actigraphy, the group with moderate-to-severe symptoms tended to have longer sleep latency, more frequently awake after sleep, and poorer sleep efficiency than the other groups (Figure 1). Patients with more severe disease activity had poorer quality of life with a mean IBDQ of 190 in remission, 159 in mild, and 134 in moderate-to-severe group (p&amp;lt;0.001). Conclusion Poor sleep quality is common among IBD patients, even those with clinical remission. Those with more severe symptoms had poorer sleep quality and worse quality of life. Sleep assessment and treatment should be integrated into IBD standard clinical care.

P913 Intestinal Ultrasound in paediatric Crohn’s disease reduces the need for subsequent ileocolonoscopy

Abstract Background Approximately 20% of patients with Crohn's disease (CD) are diagnosed during childhood (pCD). At diagnosis, the vast majority (87%) of patients with pCD demonstrate severe disease activity.(1) Severe disease activity necessitates intensive treatment followed by frequent blood tests, faecal calprotectin tests, and endoscopic procedures. Ileocolonoscopy is burdensome for the patient, as bowel preparation and general anaesthesia are needed, and furthermore, the procedure is costly. In recent European guidelines for pCD management, Intestinal Ultrasound (IUS) is recommended for clinical follow-up. Our objective was to investigate the extent to which patients with pCD underwent subsequent endoscopy after having IUS performed during their follow-up regimen. Methods We conducted a retrospective descriptive cohort study, encompassing all patients with pCD at a referral center (Department of Paediatric and Adolescence Medicine, Copenhagen University Hospital, Amager and Hvidovre) who had undergone a minimum of one ultrasound examination over a 2.5-year period (May 1, 2021, to November 1, 2023). Results A total of 29 patients with pCD were enrolled in the study. Demographic data can be found in Table 1. The median follow-up since time of diagnosis was 40 months (interquartile range (IQR) 30-57). Time to the first IUS examination after diagnosis was median 28 months (IQR 13-49). The indications for IUS were as follows: Clinical suspicion of disease activity and/or elevated faecal calprotectin levels (66% of cases), evaluation of disease activity after initiating biologic therapy (10%), assessment of disease activity status (14%), suspicion of treatment failure (7%) and other indications (3%). Following the IUS procedure, 10% of patients subsequently underwent ileocolonoscopy, which was performed within 11, 14, or 53 days after IUS. Among the remaining 90% of patients, 14% underwent ileocolonoscopy 8-16 months after the IUS procedure, while 76% never had a repeat ileocolonoscopy performed after a median follow-up of 342 days (IQR 247-441) after IUS. Conclusion In 90% of patients with pCD IUS can be used to evaluate disease activity without the necessity for an ileocolonscopy in the subsequent 12 moths of follow up.

P043 RIPK3 – a new marker for assessment of activity in Crohn’s disease

Abstract Background RIPK3 (Receptor Interacting Protein Kinase-3) is a key molecule involved in the process of necroptosis. Necroptosis is a regulated form of cell death that involves the activation of specific signaling pathways leading to cell lysis. The released endogenous molecules - DAMPs (Danger Associated Molecular Patterns) activate the immune system and lead to inflammation. This relationship suggests a role for necroptosis in the pathogenesis of IBD (Inflammatory Bowel Disease). Methods The aim of the study was to evaluate RIPK3 expression in patients with Crohn's disease (CD) according to disease activity and some clinical parameters. Tissue expression of RIPK3 in the inflamed areas of 85 patients with Crohn's disease was determined immunohistochemically. The CDAI (Crohn’s Disease Activity Index) was used to assess activity, and the Montreal Classification to determine disease location and bahavior. Results A correlation was found between RIPK3 expression and CDAI (p=0.038), with patients in remission having the lowest expression (154.67), while patients with severe activity had overexpression of the marker (180.0) (Fig.1). According to the localization of CD, a significant difference was found in the expression of RIPK3 (p&amp;lt;0.05), with the highest expression of the marker in the ileum (L1) and colon (L2) with involvement of the upper GIT (L4) – L1+L4 (225.50) and L2 + L4 (218.00). Isolated involvement of terminal ileum (L1) was characterized by the lowest expression of the marker, while patients with colonic localization (L2) had high expression of RIPK3 (184.87). Regarding disease behavior, it was found that the highest expression of the marker is in the patients with phenotype B2+B3 – both stricturing and penetrating disease, followed by inflammatory disease (B1) (Fig.2). Perianal disease further increased RIPK3 expression, with patients with concurrent perianal disease showing high expression of the marker (181.85 vs. 167.86 for those without perianal disease; p&amp;lt;0.05). Conclusion High RIPK3 expression in CD patients correlated with severe disease activity as measured by CDAI, involvement of upper GIT - L1+L4 and L2+L4, stricturing with penetrating disease - B2+B3 and concurrent perianal disease.

P308 CPa9-HNE: A NEUTROPHIL-DERIVED FRAGMENT OF CALPROTECTIN MEASURED IN SERUM CAN MONITOR ENDOSCOPIC AND CLINICAL DISEASE ACTIVITY IN ULCERATIVE COLITIS

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) presenting in remitting ulcerations of the colonic mucosa and submucosa. Mucosal healing is therefore an important treatment target. While fecal calprotectin is a common biomarker used to monitor mucosal healing in UC, patient compliance is low due to a preference for serological markers. This study aimed at investigating the association of serum calprotectin [CPa9-HNE], a non-invasive neo-epitope biomarker of neutrophil activity, with both clinical and endoscopic disease activity in UC. Methods The cohort included 49 patients with active UC and 50 and healthy controls (HC). Endoscopic and clinical disease activity was assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and the full Mayo score. Serum calprotectin [CPa9-HNE] was measured, reflecting a human neutrophil elastase-derived fragment of calprotectin. Spearman’s rank correlation was applied. Group differences were evaluated using Kruskal-Wallis with Dunn‘s test, bonferroni corrected for MCP. Diagnostic and discriminative capabilities were assessed using receiver operating characteristic (ROC) statistics with are under the curve (AUC). Results CPa9-HNE was significantly elevated in patients with UC compared to HC (ng/ml [IQR]: 32.4 [29.0–52.3] vs. 26.0 [22.6–29.0], p&amp;lt;0.0001) and presented acceptable discriminative capabilities (AUC [95% CI]: 0.77 [0.67–0.87], p&amp;lt;0.0001). CPa9-HNE showed a moderate positive correlation to UCEIS and Mayo (ρ=0.42; ρ=0.48, both p&amp;lt;0.01). When patients were stratified according to endoscopic disease activity (UCEIS), CPa9-HNE was significantly elevated in patients with severe disease compared to those with mild disease (ng/ml [IQR]: 55.6 [40.9–66.4] vs. 28.9 [24.6–31.1], p&amp;lt;0.01) and could accurately discriminate between the two groups (fig 1A-B). Similarly, when patients were grouped according to the full Mayo score, CPa9-HNE was significantly elevated in patients with mild vs. severe disease (29.1 [24.3–32.4] vs. 62.9 [55.2–67.5], p&amp;lt;0.01) and moderate vs. severe disease (32.0 [29.2–39.2] vs. 62.9 [55.2–67.5], p&amp;lt;0.01), and could accurately discriminate between the groups (fig 1C-E). Conclusion CPa9-HNE was elevated in patients with UC compared with healthy subjects. Furthermore, CPa9-HNE accurately discriminated between patients with mild and severe endoscopic disease based on the UCEIS score, as well as between patients with mild, moderate, and severe clinical disease activity according to the full Mayo score. These findings highlight the potential use of CPa9-HNE as a non-invasive tool to monitor both endoscopic and clinical disease activity in UC, with the potential of guiding treatment decisions and better aligning with patient preferences.

P750 Endoscopic balloon dilation associated with biological therapy in Crohn's Disease strictures: a single center experience

Abstract Background Symptomatic luminal stricture in Crohn’s Disease (CD) occurs in up to 20% of patients at the diagnosis and in more than 50% during their lifetime. A considerable percentage of patients often require further surgery for post-operative CD recurrence, with a consequent increased burden of short bowel syndrome. In this scenario, combining biological therapy with endoscopic balloon dilation (EBD) could potentially reduce this risk. Our study aimed to evaluate the efficacy of EBD combined with biologic therapy in symptomatic gastrointestinal strictures in CD patients. Methods We conducted a retrospective study including consecutive CD patients who underwent EBD for low gastrointestinal strictures from December 2015 until November 2022 at our tertiary IBD Center. Subsequent subocclusive/occlusive episodes, the need for steroids, and surgery due to CD stenosis were evaluated during a follow-up period of 6 and 12 months. Results A total of 52 patients treated with EBD with an overall number of 55 strictures were included. The mean age was 46,8 (18-77) years. The median of disease duration was 9 (0-42) years. Among the total of 55 studied strictures: 14 (25%) in patients with active smoking, 21 (38%) with increased CRP values at the time of dilation, 43 (78%) had evidence of moderate or severe endoscopic disease activity with ulcerative lesions at stricture site. Anastomotic strictures accounted for 26 (47%) of all 55 strictures. The remaining 29 (53%) were de novo stricture: 8 (15%) ileal, 11 (20%) at ileocecal valve, 4 (7%) colonic, and 6 (11%) anal . Forty-two patients (76%) were under biologic therapy at the time of EBD and 2 (4%) started after EBD. EBD technical success was reported in 60% of the procedures, and no adverse events were recorded. After 6 months from EBD, at univariate analysis, increased CRP at the time of dilation resulted in a risk factor for the need for steroids (OR 14,63, IC 2,690 to 71,50; p-value = 0,0006, Table 2). Concomitant biological therapy, active smoke, and the presence of ulcerative lesions did not show a significant correlation with considered outcomes. After 12 months from EBD, concomitant biological therapy resulted in being a protective factor for surgery (OR 0,06; IC 0,005 to 0,502; p-value=0,0047), while subocclusive and occlusive events were less frequent in anastomotic strictures than ileal stenosis (OR 0,07; IC 0,005 to 0,651; p-value=0,0152). Conclusion In patients with CD undergoing EBD for intestinal CD stricture, concomitant biological therapy reduces the risk of surgery for CD stenosis recurrence. Further prospective and controlled studies are underway to confirm these observations.

P940 A glance into paediatric Inflammatory Bowel Disease in Australasia – Crohn’s Colitis Cure (CCC) data insights program

Abstract Background Around 10% of people with inflammatory bowel diseases (IBD) are diagnosed in childhood1. Clinical manifestations are known to differ in children compared to adults2,3. This study aims to describe the real-world characteristics of children with IBD. Methods Crohn’s Colitis Care (CCCare) is an IBD-specific electronic medical record (EMR) used at IBD centres across Australasia. Data feed into a de-identified clinical quality registry (CQR), which was interrogated in November 2023. All children (&amp;lt;18 years at time of extract) under active care (encounter within 14 months) were included. Results Clinical data from 162 children across 14 centres were available for analysis. Of these, 64.8% (n=105) had Crohn’s disease (CD), 31.5% (n=51) ulcerative colitis (UC) and 3.7% (n=6) IBD-unclassified. There was a roughly equal split in gender (male=55.0%), with a minority aged &amp;lt;10 years (9.9%, n=16). The mean recorded body mass index was 20.5kg/m2 (n=101 with BMI data), with 78.2% in the ‘normal’ range (18.5-24.9kg/m2). Five patients (5.0%) were ‘underweight’ (&amp;lt;18kg/m2), and 16.8% (n=17) were overweight or obese (&amp;gt;25kg/m2). Only 7.4% (n=12) were currently receiving steroids, and over half (55.6%, n=90) had received an advanced therapy (biologic or small molecule). Few reported incontinence (n=5, 3.1%), and 6% (n=9) had an IBD-related surgery recorded. Around 20% (11/56) had current or previous fistulising CD. On most recent data, the mean faecal calprotectin was 637μg/g, C-reactive protein 6.1mg/L and ESR 9.4mm/hr. In those with UC, 43.7% had either moderate (S2) or severe (S3) disease activity at last assessment (Figure 1). In those with CD, 31.1% had either stricturing (B2, 21.5%) or penetrating intra-abdominal disease (abscess/perforation/phlegmon, B3, 10.6%). Conclusion This study provides a detailed real-world overview of IBD in children in Australasia, demonstrating the ability of CCCare to help collate data at scale across a large geography. Data show clear changes in phenotype over time. Such data allow for the tracking and benchmarking of outcomes over time across centres, thus promoting evidence-based care improvements. Ongoing real-world data collection is crucial in optimising management strategies and improving care outcomes. 1 - Burgess CJ et al. Paediatric Patients (Less Than Age of 17 Years) Account for Less Than 1.5% of All Prevalent Inflammatory Bowel Disease Cases. J Pediatr Gastroenterol Nutr. doi: 10.1097/MPG.0000000000002842. 2 - Seyedian SS et al. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. J Med Life. doi:10.25122/jml-2018-0075 3 - Moon JS. Clinical Aspects and Treatments for Pediatric Inflammatory Bowel Diseases. Pediatr Gastroenterol Hepatol Nutr. doi:10.5223/pghn.2019.22.1.50

P127 Sphingosine-1-Phosphate Receptor Blockade with Etrasimod alters Lymphocyte Trafficking in Crohn's Disease: Insights from High-Dimensional Phenotypic Mapping

Abstract Background The blockade of lymphocyte trafficking from the lymph nodes (LNs) towards the intestinal mucosa is an effective approach for the treatment of ulcerative colitis (UC). Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor (S1PR) modulator, which is currently also under investigation for Crohn’s disease (CD). The therapeutic mechanism of action of S1PR modulators in the context of inflammatory bowel disease (IBD) is not completely understood. It is hypothesized that both B and T- cell populations are affected by this treatment and are retained in the peripheral LNs, reducing circulating lymphocytes and resulting in fewer immune cells available to traffic in the gastrointestinal tract. Etrasimod has been reported to induce a partial and selective reduction of lymphocyte subsets in the blood of healthy subjects, but the direct effect of S1PR modulators on LN leukocytes has not been evaluated. The aim of this study was to investigate changes in leukocyte subpopulations in peripheral LNs and peripheral blood (PB) in response to S1PR inhibition with etrasimod in patients with CD. Methods CD patients with moderate to severe disease activity, participating in the Phase 2, double-blinded, non-placebo-controlled portion of the CULTIVATE trial, were eligible for this sub-study. At baseline and after 14 weeks of etrasimod induction treatment (2 or 3 mg/day), 10cc of PB and 4 ultrasound guided biopsy samples of an inguinal LN were obtained. The isolated peripheral blood mononuclear cells (PBMCs) and LN leukocyte populations, were analyzed at single cell level via high-dimensional immunophenotyping through mass cytometry (CyTOF) at both timepoints. Results We observed that in the LNs, the numbers/percentages of naïve, central and effector memory T-helper cells, as well as, of CD8+ naïve T-cells were increased after treatment with etrasimod. There was a decrease in the proportion of these cell populations in peripheral blood. Circulating naïve and memory B-cells were reduced, while these subsets where also slightly reduced in the LN compartment. Innate immune cell populations were not significantly altered. Conclusion Etrasimod induction treatment resulted in an increase of both naïve and central memory T-lymphocyte subsets in inguinal LNs, with a corresponding decrease in the periphery. The effect on the frequency of B-cells was not consistent in the LNs and PB, while innate immunotypes and T-regs, were not significantly affected. Despite the limited sample size, these selective effects were consistent with previously published PB immunophenotyping studies with etrasimod. This study was conducted as a collaboration between Amsterdam UMC and Pfizer.

P548 Ustekinumab shows favourable safety profile and drug persistence rates in patients with Crohn’s Disease – results from a tertiary IBD centre

Abstract Background Patients with Crohn’s disease (CD) often require multiple biological therapies due to loss of response. Anti-TNF drugs are generally used as first-line biologic followed by a switch of class when patients lose response. Ustekinumab (UST), an IL12/23p40 antagonist is used in CD, often after anti-TNF failure. The aim of the study was to report on outcomes of UST therapy with a median follow-up period of nearly 24 months. Methods All CD patients who commenced UST therapy were identified from EMR at two tertiary referral centers between January 2017 and December 2021. All relevant demographic and clinical data were collected. Data on clinical response (defined as a downgrade in disease activity based on clinician assessment &amp; biochemical parameters), steroid-free duration, and long-term response to UST at 52 and 104 weeks were recorded. The response was assessed clinically and supported by biomarkers, cross-sectional imaging, endoscopic data, and sustained maintenance of UST. Statistical analysis was carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0. Results A total of 249 CD patients (M=133 (53%); median age 41 years) were included, with a median follow-up period of nearly 24 months (5-79 months). 94 (38%) patients had stricturing (B2), penetrating (B3) and perianal phenotype at baseline and 104 (42%) had undergone previous resection/s. 207 (83%) had documented moderate to severe disease activity and 211 (85%) patients were exposed to at least one biologic prior to treatment with UST. 66 (27%) patients were on concomitant thiopurines at the start of treatment. 224 (90%) patients in our cohort showed clinical response to UST and all remained on treatment at the end of follow-up period. The distribution of patients as per disease activity at baseline, 52 and 104 weeks is illustrated in Figure 1. An improvement in haemoglobin levels was observed post-therapy with UST, which was statistically significant at 104 weeks (p&amp;lt;0.001), with corresponding significant reduction in faecal calprotectin levels (median reduction: 506 mcg/g to 335 mcg at 104w; p&amp;lt;0.001). Only 10 (4%) patients had side-effects which were directly attributed to UST therapy. Conclusion UST is an effective therapeutic option in CD for both bio-naïve and previous biologic failure patients. Although our cohort had a large proportion of patients with complicated and refractory disease, clinical response was observed, regardless of their previous exposure status to biologics, and disease phenotype. UST appears to be well tolerated with a reasonable safety profile. UST has good drug-persistence rates making it economically feasible in the long term. Clinicians could safely continue UST for longer durations to manage CD.

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents: data from the ENEIDA registry.

Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF. To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. Retrospective observational study. Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

Clinical characteristics and disease course before and after SARS-CoV-2 infection in a large cohort of systemic sclerosis patients.

The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis (SSc) and assess the impact of SSc features on the clinical course of COVID-19. In this multicenter, retrospective study, SSc patients with COVID-19 were included. Clinical features of SSc, along with detailed COVID-19 data, were extracted from medical records and patient interviews. The study included 112 patients (mean age 51.4 ± 12.8 years; 90.2% female). SSc-associated interstitial lung disease (ILD) was evident in 57.1% of the patients. The findings revealed hospitalization in 25.5%, respiratory support in 16.3%, intensive care unit admission in 3.6%, and a mortality rate of 2.7% among SSc patients with COVID-19. Risk factors for respiratory failure, identified through univariate analysis, included ILD (OR: 7.49, 95% CI: 1.63-34.46), ≥1 comorbidity (OR: 4.55, 95% CI: 1.39-14.88), a higher physician global assessment score at the last outpatient visit (OR 2.73, 95% CI: 1.22-6.10), and the use of mycophenolate at the time of infection (OR: 5.16, 95 %CI: 1.79-14.99). Notably, ≥1 comorbidity emerged as the sole significant predictor of the need for respiratory support in COVID-19 (OR: 5.78, 95% CI: 1.14-29.23). In the early post-COVID-19 period, 17% of patients reported the progression of the Raynaud phenomenon, and 10.6% developed new digital ulcers. Furthermore, progression or new onset of dyspnea and cough were detected in 28.3% and 11.4% of patients, respectively. This study suggests a potential association between adverse outcomes of COVID-19 and SSc-related ILD, severe disease activity, and the use of mycophenolate. Additionally, it highlights that having comorbidities is an independent risk factor for the need for respiratory support in COVID-19 cases.

Impact of disease activity on patient-reported subjective cognitive decline in patients with rheumatoid arthritis

Aim: To evaluate the association of disease activity with patient-reported subjective cognitive decline (SCD) in patients with rheumatoid arthritis (RA) stratified by age. Methods: A cross-sectional analysis using data from the CorEvitas RA registry was utilized. The clinical disease activity index (CDAI) was used along with patient-reported problems thinking, age, and gender. The association of CDAI with patient-reported SCD was estimated using logistic regression models adjusted for sociodemographic characteristics, comorbidities, RA disease characteristics, and medication use. Additional models estimated and tested the moderating effect of patient age (&lt; 55 years vs. ≥ 55 years). Results: A total of 3,041 out of 33,537 patients (9.1%), reported SCD with a mean CDAI of 16.2 [standard deviation (SD): 12.5] vs. 10.1 (SD: 10.8) in those who did not. The adjusted odds ratio (OR) for low, moderate, and severe disease activity vs. remission was 2.17 [95% confidence intervals (CI): 1.88–2.50], 3.25 (95% CI: 2.82–3.75), and 3.84 (95% CI: 3.29–4.48) respectively. Age had a moderating effect with the association of disease activity and self-reported SCD more prevalent in those aged &lt; 55 years. The ORs for low, moderate, and severe disease activity were 3.37, 5.59, and 5.76 respectively for age &lt; 55 vs. 1.90, 2.67, and 3.37 respectively for age ≥ 55 (P = 0.0001). The patient global component of CDAI displayed the highest OR of risk for SCD broken out by quartiles (1, 1.62, 2.80, and 4.55). Conclusions: Increasing disease activity is associated with a higher likelihood of patient-reported SCD. The effect was more pronounced in younger RA patients and patients with a higher patient global score.