Physician Global Assessment Research Articles

Capturing the Range of Disease Involvement in Localized Scleroderma: The Localized Scleroderma Total Severity Scale.

Juvenile localized scleroderma (jLS) is a chronic autoimmune disease commonly associated with poor outcomes, including contractures, hemiatrophy, uveitis, and seizures. Despite improvements in treatment, >25% of patients with jLS have functional impairment. To improve patient evaluation, our workgroup developed the Localized scleroderma Total Severity Scale (LoTSS), an overall disease severity measure. LoTSS was developed as a weighted measure by a consensus process involving literature review, surveys, case vignettes, and multicriteria decision analysis. Feasibility was assessed in larger Childhood Arthritis and Rheumatology Research Alliance groups. Construct validity with physician assessment and inter-rater reliability was assessed using case vignettes. Additional evaluation was performed in a prospective patient cohort initiating treatment. LoTSS severity items were organized into modules that reflect jLS disease patterns, with modules for skin, extracutaneous, and craniofacial manifestations. Construct validity of LoTSS was supported by a strong positive correlation with the Physician Global Assessment (PGA) of severity and damage and weak positive correlation with PGA-Activity, as expected. LoTSS was responsive, with a small effect size identified. Moderate-to-excellent inter-rater reliability was demonstrated. LoTSS was able to discriminate between patient subsets, with higher scores identified in those with greater disease burden and functional limitation. We developed a new LS measure for assessing cutaneous and extracutaneous severity and have shown it to be reliable, valid, and responsive. LoTSS is the first measure that assesses and scores all the major extracutaneous manifestations in LS. Our findings suggest LoTSS could aid assessment and management of patients and facilitate outcome evaluation in treatment studies.

A264 IDENTIFYING CLINICAL PREDICTORS FOR SUCCESS OF EXCLUSIVE ENTERAL NUTRITION INDUCTION THERAPY IN PEDIATRIC CROHN DISEASE

Abstract Background Current treatments for IBD focus on reducing inflammation, mostly through suppression of the immune system. Exclusive enteral nutrition (EEN) is recognized as the first line therapy for mild-to-moderate luminal pediatric Crohn disease patients pCD. Although EEN is safe, as it does not suppress the immune system, it poses considerable challenges to patients, mostly due to palatability and monotony of the formula and treatment costs. Moreover, the efficacy of EEN varies greatly from patient to patient. Therefore, there is a need to distinguish between responders and non-responder patients. Aims Identify clinical features associated with efficacy of EEN induction therapy and apply machine learning to build a classifier to identify EEN non-responders. Methods The Canadian Children Inflammatory Bowel Disease Network prospectively enrolled and followed new onset pediatric IBD cases. Prospective data for 308 pCD with EEN as their first treatment for CD are available. Patients with weighted Pediatric CD Activity Indexes (wPCDAI) collected after at least 4 weeks on EEN were compiled into a dataset (n=108). For this analysis, treatment response was defined as a wPCDAI reduction of at least 12.5 points of a patient’s wPCDAI baseline score. The dataset includes 26 features for each of the 108 pCD patients at time of diagnosis. This included blood test results (Hgb, ESR, CRP, Alb, Htc, Plt), Paris Classifications, height, and weight Z-scores, as well as wPCDAI, SES-CD (simple endoscopic score, CD), PGA (physician global assessment), and Mayo scores. Odds ratios were calculated to determine whether any features were associated with response to EEN induction therapy. Then, the most relevant features were identified with regularization techniques and a machine learning classifier for predicting response to EEN was built. Results Results showed that the appropriate subset of features to include for optimal accuracy over model simplicity are n=4 (PUCAI, PGA, SES-CD scores, and hematocrit). Also, an increase in PGA score (e.g., moving from “mild disease” to “moderate disease”) was associated with an increase in the chance of EEN failure (OR 3.1, 95% CI [1.7,5.8], p=0.0001). The best classifier for predicting EEN response was a random forest consisting of 20 decision trees. The classifier achieved an area under the ROC curve of 0.75 ± 0.07 Conclusions Our results suggest that it is possible to produce a classifier capable of predicting EEN clinical remission with an accuracy over 60%. Higher PGA, PUCAI, and SES-CD scores show potential for predicting patients less likely to respond to EEN induction. This research has the potential to provide better quality of life for children who live with IBD. Funding Agencies CIHRIMAGINE SPOR Network , Women and Children's Health Research Institute

Efficacy and Durability of Intravenous Ertapenem Therapy for Recalcitrant Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a debilitating follicular skin disorder in which bacterial colonization is typical. Oral antibiotic efficacy can be unreliable; however, selective intravenous antibiotics, specifically ertapenem, may provide favorable clinical outcomes. To explore optimal course duration, efficacy, and patient satisfaction associated with intravenous ertapenem for HS. This retrospective review of the medical records of 98 patients with HS between 2018 and 2022 measured and evaluated patient outcomes before and after treatment with intravenous ertapenem. Participants were followed up in a telephone survey assessing patient perspectives and satisfaction. All of those included in this study received medical care from the Albert Einstein College of Medicine's Montefiore HS Center. Patients were treated with 1 g of ertapenem that was self-administered at home through a peripheral intravenous central catheter using an elastomeric pump for 12 to 16 weeks. Antiandrogens and immunomodulatory biologic therapies initiated prior to ertapenem were maintained throughout the treatment course. The primary outcomes, encompassing clinical severity (evaluated through the HS Physician Global Assessment score [a 6-point scale ranging from clear to very severe] and a numerical rating scale for pain [an 11-point scale in which a score of 0 indicates no pain and a score of 10 indicates the worst possible pain]) and markers of inflammation (such as leukocytes, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6), were measured at baseline, the midcourse of intravenous ertapenem treatment, at the end of the course, and posttherapy. Bacterial abundance was also examined at these 4 points, and patient satisfaction was assessed during follow-up. A total of 98 patients (mean [SD] age, 35.8 [13.0] years; 61 [62.2%] female) with HS were treated with intravenous ertapenem. The self-reported racial distribution included 3 individuals identifying as Asian (3.1%), 59 as Black/African American (60.2%), 13 as White (13.3%), and 23 as either other or unknown (23.5%). Additionally, 24 participants (24.5%) reported Spanish/Hispanic/Latino ethnicity. The mean (SD) treatment duration spanned 13.1 (4.0) weeks, with posttherapy follow-up occurring after 7.8 (3.6) weeks. From baseline to posttherapy follow-up, significant reductions were found in the mean (SD) HS Physician Global Assessment scores (3.9 [1.0] vs 2.7 [1.2]; P < .001) and the numerical rating scale for pain (4.2 [3.3] vs 1.8 [2.7]; P < .001), C-reactive protein (5.4 [11.4] vs 2.4 [2.0] mg/dL; P < .001), interleukin-6 (25.2 [21.1] vs 13.7 [13.9]; P < .001), and leukocytes (11.34 [3.9] vs 10.0 [3.4]; P < .001). At follow-up, 76 patients (78.0%) participated in the telephone survey, where 63 (80.3%) reported medium to high satisfaction; further, 69 (90.8%) would recommend ertapenem to other patients. In this retrospective review of medical records and telephone survey, treating HS with intravenous ertapenem, administered for a mean of 13 weeks, was associated with improvement in clinical and inflammatory markers, as well as heightened patient satisfaction. Nonetheless, this approach should be monitored for the emergence of antimicrobial resistance given a longer than standard treatment course.

A250 CYTOKINE MULTI-OMICS AND MACHINE LEARNING IDENTIFY MIP1ALPHA AS A NOVEL MEDIATOR IN INFLAMMATORY BOWEL DISEASE

Abstract Background Macrophage inflammatory protein 1 alpha (MIP1a) is a proinflammatory cytokine previously related to murine models of inflammatory bowel disease (IBD), but not definitively in the human disease. MIP1a acts as a chemoattractant of immune cells from the blood to the gut mucosa. We aimed to delineate the alterations to MIP1a and macrophages in relation to a range of IBD severity. Aims To characterize the changes to MIP1a production and localization in response to disease activity in IBD. Methods Both IBD (n=63) and control patients (n=118) were enrolled in this study (HSREB 6033229). Cytokine profiles were investigated using a 17-plex multi-fluorescent bead-based immunoassay (FirePlex, Abcam, Cambridge, UK) on serum from a subset of patients. Disease activity and macrophage levels were extracted from the clinical record. Activity was quantified using the Physician Global Assessment Score. Machine learning (ML) was performed with custom R scripts utilizing the tidymodels package (version 1.1) to determine the optimal model. Immunohistochemistry (IHC) was used to localize MIP1a in patient biopsies and quantified using QuPath software (v0.4). Results An extreme gradient boost ML model was found to have optimal sensitivity and specificity for predicting disease activity based on serum cytokine levels. Within this model lower levels of serum MIP1a were associated with higher severity of IBD activity. However, in GI mucosal biopsies, the percentage of MIP1a positive cells in colon tissue increased with the severity of IBD. Macrophage concentrations in the peripheral blood were higher in patients on prednisone, and relatively similar across all other medications used in our cohort. Conclusions With the data collected, we identify MIP1a as a possible prognostic tool for quantifying IBD activity. Funding Agencies CIHR

Real-world effects of Yishen Tongbi decoction for rheumatoid arthritis: protocol for a prospective, observational, multicenter cohort study with validation against double-blind, randomized, controlled trial.

Introduction: Rheumatoid arthritis (RA) is a globally challenging and refractory autoimmune disease, constituting a serious menace to human health. RA is characterized by recurrent pain and is difficult to resolve, necessitating prolonged medication for control. Yishen Tongbi decoction is a traditional Chinese herbal compound prescribed for treating RA. We have completed a 3-year RCT study that confirmed the clinical efficacy of Yishen Tongbi decoction for RA. Notably, we observed a faster clinical remission rate compared to MTX by week 4 of treatment. In our forthcoming study, we intend to conduct a comprehensive assessment of the efficacy and safety of Yishen Tongbi decoction in the real-world treatment of RA through a prospective study. Methods and analysis: This prospective, multicenter, real-world observational study will be conducted at two designated centers in China from October 2023 to August 2025. The study will include 324 patients with active rheumatoid arthritis. One group will receive Yishen Tongbi decoction combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The other group will receive standard treatment. Standard treatment can be further divided into subgroups: csDMARDs, targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and biologic disease-modifying antirheumatic drugs (bDMARDs). In each group, the number of tender joints, number of swollen joints, pain score, patient global assessment, physician global assessment, disease activity index (DAS28-ESR or DAS28-CRP), clinical disease activity index (cDAI), simplified disease activity index (sDAI) and relevant laboratory data will be compared. Clinical indicators and disease activity of the patients will be assessed at baseline, week 4 and week 12 after the initiation of treatment. The primary outcome will be the American College of Rheumatology 20% improvement criteria (ACR20) attainment rate among patients at week 12 after treatment. Every adverse event will be reported. Ethics and dissemination: This study has been approved by the Ethics Committee of the first affiliated Hospital of Guangzhou University of traditional Chinese Medicine (NO.K-2023-009). The results of the study will be published in national and international peer-reviewed journals and at scientific conferences. The researchers will inform participants and other RA patients of the results through health education. Clinical Trial Registration: https://www.chictr.org.cn/index.html, identifier ChiCTR2300076073.

Clinical outcomes and cost savings of a nonmedical switch to a biosimilar in children/young adults with inflammatory bowel disease.

The safety, efficacy, and cost savings associated with biosimilar medications are well established. However, a lack of pediatric data exists surrounding clinical outcomes when switching from an originator to a biosimilar. Our primary aim is to evaluate clinical outcomes following a nonmedical switch from the infliximab originator to a biosimilar in children and young adults with inflammatory bowel disease (IBD).Our secondary aim is to estimate cost savings associated with this switch. A quality improvement project was implemented to establish safe switching protocols, then those patients who underwent a nonmedical switch from the infliximab originator to the biosimilar were retrospectively reviewed. Demographic data, physician global assessments (PGAs), and laboratory values were recorded 1 year pre- and post-switch. Continuation rates on the biosimilar were reported at 6 and 12 months. Cost savings were estimated using two different pricing models. Fifty-threepatients underwent a nonmedical switch. Laboratory values including inflammatory markers, infliximab levels, and PGAscores remained similar when assessed pre- and post-switch. No infusion reactions or antidrug antibody development occurred. Two patients reported psoriasis-like rashes. Five patients switched back to the originator during the study period. There were 379 biosimilar infusions completed with an estimated total cost savings of $11,260 (average sales price) and $566,223 (wholesale acquisition cost). Clinical remission rates, inflammatory laboratory markers, serious adverse events, infliximab levels, and antidrug antibodies remained similar after aone-time nonmedicalswitch to an infliximab biosimilar. Nonmedical switching to biosimilars resulted in significant cost savings.

Psychometric validation of the Psoriasis Symptom Scale, Functional Assessment of Chronic Illness Therapy-Fatigue and pain-Visual Analogue Scale in patients with generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease associated with considerable patient burden. The Psoriasis Symptom Scale (PSS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and pain-Visual Analogue Scale (pain-VAS) are patient-reported outcomes (PROs) that have not yet been validated in patients with GPP. To evaluate the psychometric properties of the PSS, FACIT-Fatigue and pain-VAS using data from Effisayil 1, a randomised trial of spesolimab in patients with moderate-to-severe GPP. Inter-item correlations and confirmatory factor analysis (CFA) were performed using Week 1 data. Internal consistency was assessed with Cronbach's α coefficient using baseline and Week 1 data. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs); change data for the GPP Physician Global Assessment total score and pustulation subscore were used to define a stable population. Convergent validity was assessed at baseline and Week 1 using Spearman's rank-order correlations. Known-groups validity was measured by analysis of variance using Week 1 data. Ability to detect change from baseline to Week 1 was evaluated by analysis of covariance. Inter-item and item-to-total correlations were moderate or strong for most PSS and FACIT-Fatigue items. CFA demonstrated the unidimensionality of the PSS and FACIT-Fatigue, with high factor loadings for most items (PSS range, 0.75-0.94; FACIT-Fatigue range, 0.11-0.93) and acceptable fit statistics. Both scores demonstrated internal consistency (Cronbach's α, 0.71 and 0.95, respectively). The PSS, FACIT-Fatigue and pain-VAS demonstrated test-retest reliability (ICCs ≥0.70) and good evidence of convergent validity. Furthermore, the PROs could differentiate between known groups of varying symptom severity (range, p < 0.0001-0.0225) and detect changes in symptom severity from baseline to Week 1 (range, p < 0.0001-0.0002). Overall, these results support the reliability, validity and ability to detect change of the PSS, FACIT-Fatigue and pain-VAS as PROs in patients with GPP.

Efficacy and safety of peppermint oil for the treatment in Japanese patients with irritable bowel syndrome: a prospective, open-label, and single-arm study

BackgroundIn Europe, an herbal medicine containing peppermint oil is widely used in patients with irritable bowel syndrome (IBS). In Japan, however, no clinical evidence for peppermint oil in IBS has been established, and it has not been approved as a drug for IBS. Accordingly, we conducted a clinical study to confirm the efficacy and safety of peppermint oil (ZO-Y60) in Japanese patients with IBS.MethodsThe study was a multi-center, open-label, single-arm, phase 3 trial in Japanese outpatients with IBS aged 17–60 years and diagnosed according to the Rome III criteria. The subjects were treated with an oral capsule of ZO-Y60 three times a day before meals, for four weeks. The efficacy of ZO-Y60 was evaluated using the patient’s global assessment (PtGA), IBS symptom severity score, stool frequency score, stool form score, and physician’s global assessment (PGA). The safety of ZO-Y60 was also assessed.ResultsSixty-nine subjects were treated with ZO-Y60. During the four-week administration of ZO-Y60, the improvement rate of the PtGA was 71.6% (48/67) in week 2 and 85.1% (57/67) in week 4. It was also suggested that ZO-Y60 is effective against any type of IBS (IBS with constipation, IBS with diarrhea, and mixed/unsubtyped IBS). The improvement rate of the PGA was 73.1% (49/67) in week 2 and 85.1% (57/67) in week 4, also confirming the efficacy of ZO-Y60. Adverse events were observed in 14 subjects (20.3%), however, none of these adverse events were categorized as serious.ConclusionThe efficacy of treatment was confirmed, subjective symptoms were improved, as was observed in previous clinical studies of ZO-Y60 conducted outside of Japan. All adverse reactions were previously known and were non-serious. These findings suggest that peppermint oil may be effective in the Japanese population and that it has an acceptable safety profile.Trial registrationJAPIC Clinical Trials Information number: JapicCTI-121727 https://jrct.niph.go.jp/en-latest-detail/jRCT1080221685. Registration date: 2012–01-10.

Targeting histamine receptor 4 in cholinergic urticaria with izuforant (LEO 152020): results from a phase IIa randomized double-blind placebo-controlled multicentre crossover trial.

Cholinergic urticaria (CholU) is a common subtype of chronic inducible urticaria, where signs and symptoms (e.g. pruritic wheals and angioedema) are triggered by sweating due to physical exercise, passive warming and by other sweat-inducing situations. While guidelines recommend treatment with second-generation H1 antihistamines, approximately 90% of patients report uncontrolled disease. Targeting the histamine 4 receptor (H4R) has shown promise in preclinical/clinical studies of allergic/inflammatory diseases. Izuforant (LEO 152020) is a selective oral H4R antagonist with expected dual antipruritic and anti-inflammatory effects. To assess the effects of izuforant in adults with CholU, a common type of chronic urticaria driven by histamine and characterized by high skin levels of H4R expression. This was a phase IIa randomized double-blind placebo-controlled multicentre crossover trial where patients with CholU with an inadequate response to ≥ 1 standard dose of H1 antihistamine received izuforant 100 mg twice daily or placebo (EUCTR2020-004961-38-DE; NCT04853992). The primary endpoint was change from baseline in Urticaria Activity Score. Exploratory endpoints included CholU activity score over 7 days, urticaria control test, Physician Global Assessment, patient global assessment of severity (PGA-S), provocation tests, Dermatology Life Quality Index and CholU quality of life (CholU-QoL). Pharmacokinetic and pharmacodynamic parameters, and serum biomarkers were assessed, as well as safety and tolerability. Nineteen patients were randomized and included in the full analysis set; 18 completed treatment [mean (SD) age 29.5 (9.8) years; mean (SD) CholU duration 8.0 (6.3) years]. The primary and most of prespecified exploratory endpoints were not met; there were significant improvements in PGA-S for izuforant vs. placebo (P = 0.02), and nonsignificant improvements for other endpoints in quality of life and histamine skin prick test. All adverse events (AEs) experienced with izuforant were considered mild. The most frequently reported (> 1 patient) were nausea (three patients) and upper abdominal pain (two patients), occurring more frequently with izuforant vs. placebo (one patient each). There were no treatment-related serious AEs and no patient receiving izuforant discontinued the study. Treatment with izuforant did not cause downregulation of H4R. This is the first study to explore the role of H4R as a therapeutic target in urticaria. Targeting H4R with izuforant was well tolerated but did not demonstrate significant improvements vs. placebo in the primary endpoint and all but one prespecified exploratory endpoint in CholU.

Real-world data on the effectiveness of brodalumab in patients with moderate-to severe plaque psoriasis in the Greek clinical setting (the BrIDGE study).

Despite that brodalumab's efficacy and safety have been assessed in randomized clinical trials, real-life data remain scarce. BrIDGE was an observational, prospective, single-cohort, multicentre study that recruited patients with moderate-to severe plaque psoriasis in Greece. The primary objective was to assess the proportion of patients who achieved Psoriasis Area and Severity Index (PASI)100 after 24 weeks. Other endpoints included: the maintenance of PASI90/100 through to 104 weeks, the short-term response [PASI75/90/100 and static Physician's Global Assessment (sPGA) 0/1] to brodalumab at 12-16 weeks and time to complete clearance. Moreover, we explored the change in quality of life [Dermatology Life Quality Index (DLQI) 0/1] and adherence to brodalumab. Two hundred patients who were initiating treatment with or switching to brodalumab, were recruited. Analyses were conducted using the as observed data and three imputation approaches were also applied for the missing data (last observation carried forward, 'worst case' and 'best case' scenario). Continuous variables were reported using summary statistics, whereas categorical variables were reported in frequency tables. Based on the 'as observed data', 42.0% of patients achieved PASI100 at Week 24 after 25.9 ± 3.5 weeks and 65% of patients attained PASI100 at Week 104. In total, 70.2%, 47.5% and 32.0% achieved PASI75/90/100, respectively, whereas 72.6% of patients achieved sPGA 0/1, at Weeks 12-16. With respect to sPGA status 82.8%, 89.2% and 92.5% of patients achieved sPGA 0/1 at Weeks 24, 52 and 104, respectively. The time to achieve PASI100 at Weeks 12-16 was 13.7 ± 1.3, 52.1 ± 3.4 weeks at Week 52 and 105.5 ± 4.8 weeks at Week 104. Mean DLQI and Psoriasis Symptom Inventory (PSI) scores decreased by 11.4 ± 7.0 and 15.4 ± 6.5 points from baseline to Week 104, respectively. Adherence to treatment was equal to 98.9%. Brodalumab confers rapid and durable responses, as well as improvements in the quality of life of moderate-to-severe psoriasis patients.

Ustekinumab Drug Levels and Outcomes in Inflammatory Bowel Disease.

Data regarding the utility of therapeutic drug monitoring with ustekinumab (UST) are sparse. Our aim was to determine the correlation of UST levels with outcomes in a cohort of patients with inflammatory bowel disease (IBD). This was a multicenter, retrospective study of all patients with IBD who received UST from January 1, 2014 to March 1, 2022. The primary outcomes were the correlation of UST level with clinical remission (per physician global assessment), endoscopic healing [the absence of ulcers/erosions in Crohn's disease (CD) and Mayo endoscopic score ≤1 for ulcerative colitis (UC)], and normal serum C-reactive protein (CRP) (≤5mg/L). Secondary outcomes included defining optimal UST trough levels associated with favorable outcomes. A total of 71 patients (74.6% with CD; 57.7% female) were included. The median age was 39.5 years [interquartile range (IQR): 26 to 52] and 12.6% were on combination therapy with immunomodulators. Median UST trough levels were significantly higher in patients who achieved endoscopic healing at 5.4µg/mL versus 3.5µg/mL (P=0.035) and normal CRP at 5.5µg/mL versus. 3.1µg/mL (P=0.002). A cutoff UST level of 4.8µg/mL yielded the highest area under the curve (AUC) of 0.73 (95% CI: 0.61-0.80) to predict a normal CRP followed by a cutoff of 3.5µg/mL which yielded an AUC of 0.66 (95% CI: 0.52-0.81) to predict endoscopic healing. UST trough levels were significantly higher in patients who achieved a normal CRP and endoscopic healing. A cutoff UST level of 4.8µg/mL reliably predicted CRP normalization.

Effectiveness of ixekizumab for the treatment of moderate-to-severe plaque psoriasis with involvement of difficult-to-treat areas: A 52-week multicenter retrospective study.

Biological drugs have dramatically changed the approach to treating moderate-to-severe plaque psoriasis, achieving excellent skin clearance and safety outcomes. However, the management of difficult-to-treat areas (e.g., scalp, palms/soles, nails, and genitalia) still represents a challenge in psoriasis treatment. Data in the literature on difficult-to-treat sites are limited and, frequently, no specific analysis is performed during clinical trials. We conducted a 52-week, retrospective study to evaluate the effectiveness of ixekizumab in 120 patients with moderate-to-severe plaque psoriasis of at least one difficult-to-treat area (scalp, palmoplantar surfaces, nails, and genitalia). Ninety-nine patients had scalp psoriasis, 35 had involvement of the palms or soles, 27 were affected by genital psoriasis, and 22 patients reported involvement of the nails. After 1 year of treatment, 96% of patients with scalp involvement, 95.6% of patients with palmoplantar psoriasis, 95.2% of patients with genital psoriasis, and 85% of patients with nail involvement achieved a site-specific Physician's Global Assessment of 0 or 1 (clear or almost clear). No serious adverse events were observed during the study. Our study supports the effectiveness of ixekizumab in plaque psoriasis involving difficult-to-treat sites.

Characteristics and management of generalized pustular psoriasis (GPP): Experience from the Central and Eastern Europe (CEE) GPP Expert Network.

Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by widespread eruption of sterile pustules with or without systemic symptoms. This study aimed to describe the demographics of patients with GPP in Central and Eastern Europe (CEE), present the clinical characteristics of individual GPP flares and explore the current treatment landscape. Patient demographics were collected at the times of last observation and previous treatment. Characteristics of a patient's last (most recent) and most severe (from all documented episodes) flare were provided at clinician's discretion. Fifty-eight patients were recruited from 12 centres in nine CEE countries; median (range) age was 61 (16-92) years and 60.3% (35 out of 58) were female. The most common comorbidities were hypertension (43.1% [25 out of 58]) and hyperlipidaemia (32.8% [19 out of 58]). Thirty-four patients (58.6%) presented with concomitant plaque psoriasis before or during the course of GPP. Data from two separate flares were recorded in 26 individuals; in 32 patients, the most recent flare was reported as the most severe. Over 90% of patients with a flare episode classified as most severe by clinicians were hospitalized, with >75% of these individuals having a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 3 or 4. Systemic symptoms were more common in patients with a GPPGA score of 3 or 4 but were also manifest in individuals with a GPPGA score ≤2. A significant correlation was observed between a combined systemic disease score of clinical and laboratory features and both GPPGA total score (r = 0.385, p < 0.001) and GPPGA pustulation subscore (r = 0.305, p < 0.05). Considerable heterogeneity in the presentation of GPP flares was observed, both between patients and within-patient. All GPP flares were associated with a significant clinical burden, highlighting the unmet need for accurate and early diagnosis.

CYTOKINE MULTI-OMICS AND MACHINE LEARNING IDENTIFY MIP1ALPHA AS A NOVEL MEDIATOR IN INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Macrophage inflammatory protein 1 alpha (MIP1a) is a proinflammatory cytokine previously related to murine models of inflammatory bowel disease (IBD), but not definitively in the human disease. MIP1a acts as a chemoattractant of immune cells from the blood to the gut mucosa. We aimed to delineate the alterations to MIP1a and macrophages in relation to a range of IBD severity. HYPOTHESIS To characterize the changes to MIP1a production and localization in response to disease activity in IBD. APPROACH Both IBD (n=63) and control patients (n=118) were enrolled in this study (HSREB 6033229). Cytokine profiles were investigated using a 17-plex multi-fluorescent bead-based immunoassay (FirePlex, Abcam, Cambridge, UK) on serum from a subset of patients. Disease activity and macrophage levels were extracted from the clinical record. Activity was quantified using the Physician Global Assessment Score. Machine learning (ML) was performed with custom R scripts utilizing the tidymodels package (version 1.1) to determine the optimal model. Immunohistochemistry (IHC) was used to localize MIP1a in patient biopsies and quantified using QuPath software (v0.4). RESULTS An extreme gradient boost ML model was found to have optimal sensitivity and specificity for predicting disease activity based on serum cytokine levels. Within this model lower levels of serum MIP1a were associated with higher severity of IBD activity. However, in GI mucosal biopsies, the percentage of MIP1a positive cells in colon tissue increased with the severity of IBD. Macrophage concentrations in the peripheral blood were higher in patients on prednisone, and relatively similar across all other medications used in our cohort. CONCLUSIONS With the data collected, we identify MIP1a as a possible prognostic tool for quantifying IBD activity.

P834 Choosing wisely: Ustekinumab in Elderly Crohn’s Patients – A Comparative Study

Abstract Background The burden of Inflammatory Bowel Disease (IBD) in elderly patients derives from background comorbidities and the elevated risk associated with immunosuppressive treatments. In the present study, we aimed to assess the efficacy and safety of ustekinumab (UST) in elderly patients with Crohn's disease (CD). Methods This study was designed as a retrospective-cohort study including patients ≥ 60 years old (elderly) and patients &amp;lt; 60 years (non-elderly) who commenced UST for CD at a large, tertiary medical center. Outcomes were assessed by clinical response evaluation through parameters such as physician global assessment (PGA) and the Harvey-Bradshaw index (HBI), alongside assessment of clinical biomarkers, hospitalization rates, treatment persistence, and the necessity for surgical interventions. A secondary analysis was conducted of elderly patients treated with UST compared to elderly patients treated with vedolizumab (VDZ). Results In total, the primary analysis included 99 patients treated with UST (34 elderly patients and 65 non-elderly patients). Duration of follow-up was a median of 12 months (IQR 0). Elderly patients had predominantly an isolated ileal disease (68%) compared to an ileo-colonic disease (36%) in non-elderly patients (p = 0.017). The median age of onset was 68 years (IQR 64-75), and 34 years (IQR 28-42), respectively. Furthermore, elderly individuals were more likely to receive corticosteroids as their initial treatment (44% vs. 14%, &amp;lt;0.001). No differences were demonstrated in disease duration, EIM, phenotype, or previous biological therapy. Following six months of therapy, elderly patients were more likely to achieve complete clinical remission (31% vs. 12%, p = 0.035) as assessed by PGA. The elderly group experienced higher hospitalization rates during the 6-month (21% vs 4.6%, p = 0.029) and the 12-month follow-up period (15% vs. 3.1%, p = 0.045), while surgery rates were comparable between non-elderly and elderly groups (table 1). Concerning elderly UST vs elderly VDZ patients (n=69), no significant differences were observed in clinical response and remission rates between the groups after 6 and 12 months of follow up. In addition, no significant differences were shown in regard to safety (hospitalizations, surgery or therapy cessation rates). Conclusion UST is an effective treatment option in elderly CD patients. However, this population had higher hospitalization rates compared to non-elderly patients, greatly owing to age and comorbidities.

P192 Personalizing treatment for predicting response to infliximab in children with Crohn’s disease using proteomic biomarkers

Abstract Background Identifying minimally invasive diagnostic biomarkers that predict and monitor response to TNF inhibitors would enable treatment to be personalized and increase knowledge of the biological pathways associated with response or lack thereof. Methods Children and adolescents with Crohn’s disease who started treatment with infliximab (IFX) were enrolled in a prospective, multi-center (n=6) trial to identify biomarkers that predict response to IFX. Electronic case report forms were prepared by Studytrax (Macon, GA). Subjects &amp;lt;18 years of age were diagnosed with Crohn’s disease using standard clinical/pathologic criteria. Clinical evaluation and serum samples were obtained prior to initiation of IFX, after induction (dose 4), at six months, and after one year or at the time of treatment withdrawal. There were 119 subjects enrolled and 102 subjects completed induction. Non-responders (n=15) were defined prior to the 4th infusion as having a PCDAI &amp;gt; 10, an elevated Physician Global Assessment (PGA) or requiring dose escalation or medication change. Responders at the 4th infusions were either in remission (PUCAI ≤ 10) or were described as quiescent by PGA. Using the 7k SomaScan (SomaLogic; Boulder, CO) proteomics platform, quantitative protein profiles were generated from banked pre-treatment (V1) and after the three-dose induction (V2) to identify candidate protein biomarkers predictive of therapeutic response. Associations between the 7,310 proteins detected with SomaScan and response to IFX were assessed using t test. Response predictor models were developed using linear regression with backward selection. We report our preliminary findings from a discovery cohort of 56 subjects who completed induction. Results There were 15/56 (27%) non-responders and 41/56 (73%) responders at V2 after IFX induction. SomaScan analysis of the 56 individuals identified sets of differentially expressed proteins discriminating between non-responders and responders at both V1 and V2 and also defined protein signatures that changed from V1 to V2 for responders and non-responders, respectively. Strikingly, only responders demonstrated significant decreases in pro-inflammatory pathways at V2 compared to V1, thereby correlating well with anticipated reduced inflammation in responders. A 6-protein linear regression model performed with an AUC of 0.99 for predicting IFX response at pre-treatment V1. Conclusion In a discovery cohort from a multicenter, prospective trial of children and adolescents treated with infliximab, a comprehensive proteomics platform was able to identify serum proteins that are highly associated with response to infliximab and accurately predict response prior to treatment.

P984 VEST: The UK vedolizumab real life experience study in Inflammatory Bowel Disease

Abstract Background The characteristics and outcomes of patients treated with vedolizumab in routine healthcare settings have not been widely evaluated in the UK. Methods Prospective, multicentre observational study of 364 patients started on vedolizumab in UK practice from January 2017 until February 2019 using the UK IBD Registry clinical web-based tool. For the present analysis, the primary outcome was drug survival (persistence) at 1-year, defined as attendance for infusion ≥48 weeks after the first dose. Secondary outcomes were: Clinical remission (CR, based on partial Mayo score [≤1] or Harvey Bradshaw index [≤4]), physician global assessment (PGA), IBD-Control Questionnaire (IBD-Control-8, IBD-Control-VAS and individual item scores), laboratory parameters and adverse events. Results Age (mean): 44 yrs; Males: 48%; IBD duration (mean): 6 yrs; Prev. resection: 18%; Steroids at baseline: 39%; Outcomes are summarized in Table 1. 37% of CD patients were assessed as being in clinical remission at baseline. Overall, 210 (58%) continued treatment beyond 48 weeks. At 1 year, 67.1% and 52.3% of CD and UC patients were in clinical remission with a clear improvement in QoL as assessed by IBD-Control -8. There were significant improvements across each IBD-Control-8 domain, including fatigue, with few patients considering switching treatment at that point (Figure 1). Conclusion Vedolizumab was effective in clinical practice with 58% of patients remaining on treatment at one-year. Baseline status differed significantly from those recruited into RCTs. Patient reported outcomes demonstrated significant and meaningful improvements across physical, psychological, social and treatment domains.

P850 Symptomatic effectiveness of ozanimod in routine clinical care of ulcerative colitis: an interim analysis of the multicentre, prospective, noninterventional COLIBRI study

Abstract Background Ozanimod (OZA) is approved for the treatment of adults with moderately to severely active (MOD/SEV) ulcerative colitis (UC) per results of the phase 3 True North trial. Real-world data are needed to determine treatment effects in a more diverse population in clinical practice. The COLIBRI study (NCT05382715) assesses the use, effectiveness, and safety of OZA and quality of life in patients (pts) with MOD/SEV UC in a routine clinical practice setting in Germany over a period of 52 or 104 weeks. This interim analysis of COLIBRI reports baseline (BL) characteristics and evaluates the symptomatic clinical effectiveness of OZA up to Week (W) 10. Methods COLIBRI will enrol up to 380 adults with UC; the study design is shown in the Figure. Adherence to the times of visits and the diagnostic and therapeutic measures are not mandatory and will correspond to the routine processes of the respective facilities. Partial Mayo score (pMS; sum of stool frequency subscore [SFS], rectal bleeding subscore [RBS], and Physician Global Assessment), symptomatic clinical improvement, defined as either symptomatic response (decrease from BL in the combined 6-point SFS + RBS of ≥1 point and &amp;gt;30%, and decrease of ≥1 point in RBS or absolute RBS of ≤1 point) or symptomatic remission (RBS = 0 and SFS ≤1, and a decrease of ≥1 point from BL SFS), and symptomatic remission were assessed at W4 and W10. Data were collected by electronic case report forms and by the study-specific interface of the MyTARGET app (Kiel, Germany) for pt-related outcomes, which were evaluated throughout the study. Results Of 83 pts included in this interim analysis (BL and W4, n=58; BL and W10, n=39), the median (interquartile range) age of pts was 40 (29.0–53.0) years, 49 (59.0%) were female and 34 (41.0%) male, 80.7% had prior exposure to advanced therapies (AT), and 48.2% had prior exposure to ≥3 AT. Overall, 67.5% had prior tumor necrosis factor alpha inhibitor and 50.6% had prior vedolizumab use. BL pt characteristics are shown in the Table. In total, 76 pts with BL data had pMS data; the mean (SD) pMS at BL was 5.0 (2.2), and most pts fell within the moderate pMS category (44.9%). Mean (SD) pMS decreased from BL (5.0 [2.2]) to 3.9 (2.6) at W4 and to 3.5 (2.3) at W10. Symptomatic clinical improvement was achieved in 32.8% (19/58) and 51.3% (20/39) of pts at W4 and W10, respectively. Symptomatic remission was achieved in 22.4% (13/58) and 25.6% (10/39) of pts at W4 and W10, respectively. Conclusion This interim analysis of the German COLIBRI study showed that refractory pts with MOD/SEV UC receiving OZA achieved symptomatic effectiveness at W4 and W10 in a routine clinical practice setting.

P1164 Early monitoring of ustekinumab concentration after induction is related to clinical remission in ulcerative colitis &amp; Crohn`s disease - STOCUSTE study

Abstract Background Ustekinumab (UST), an anti-interleukin-12/23 antibody, is used to treat moderate to severe inflammatory bowel disease (IBD). The STOCUSTE study includes IBD patients treated with UST at four teaching hospitals in Stockholm to provide long-term follow-up data. We investigated in a real-world setting the utility of therapeutic drug monitoring (TDM) to optimize treatment and correlated the serum concentrationof UST to clinical outcomes. Methods This retrospective study includes patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) treated with UST and followed until withdrawal of treatment for any reason, or until end of study,July 31, 2021. Concentration data and dosing interval were collected at each follow-up (3, 6, 9, 12, 24,36, 48, 60 months) in relation to presence of remission defined as Physician Global Assessment (PGA)= 0. Results In total, 418 patients were included, 322 (48% females) with CD and 96 (46% females) with UC. In 229 patients the UST concentration was analyzed at least once and never in the remaining 188 patients. In general, the UST serum concentrations were above 1 μg/ml. At 3 months follow-up, patients in remission had a significant higher concentration of UST compared to non-remitting patients. (Table 1) in the total cohort, as well as when analyzed separately in UC ad CD. There was no significant difference in UST concentrations at 6 months or later between patients in remission versus non-remission for either IBD diagnosis. Further, TDM was related to higher rates of remission at 3 months of follow-up. Conclusion In this study, early measurement of serum UST (≤3 months) correlated to the clinical response. Serum concentrations at later time points were similar in patients in remission and in patients with active disease. These results from a real-world setting might partly be explained by that serum concentrations were not taken in a systematic manner.

P098 The Endoscopic Severity Score Map (ESSM): An Artificial Intelligence scoring system providing accurate, objective and localised measurements of endoscopic disease severity in ulcerative colitis

Abstract Background Commonly used scoring schemes as the Mayo Endoscopic Subscore (MES) account for disease severity only at specific (i.e., the worst) segments and do not capture disease extent. However, for an accurate assessment of disease severity in patients with ulcerative colitis (UC), the measure of the precise extent of disease activity is necessary. Alternative systems that include disease extent have been proposed (Balint 2018), but their implementation is prohibited by the time and cost constraints of comprehensively scoring each location along the entire colon. Here, we present the Endoscopic Severity Score Map (ESSM), a scoring system based on Artificial Intelligence, capable of providing an assessment of disease severity and extent in UC in a fully automated manner. Methods The ESSM consists of 3 main elements (Fig. 1): 1) a quality algorithm which selects readable frames from a colonoscopy video, 2) a scoring system which assigns an MES to each readable frame (Gutierrez Becker 2020) and 3) a camera localisation algorithm that assigns each frame to an anatomical location within the colon (Yao 2022). The ESSM was trained and tested using 4,306 sigmoidoscopy videos from phase III Etrolizumab clinical trials (Hickory NCT02100696, Laurel NCT02165215, Hibiscus I NCT02163759, Hibiscus II NCT02171429 and Gardenia NCT02136069). Results We evaluate the performance of the ESSM by first assessing the agreement of scoring as compared to centrally read MES. The agreement between central reading and the ESSM at the colon section level was high (quadratic-weighted kappa k=0.81; Tab. 1). This was comparable to the agreement between central and local reading (k=0.84), suggesting that the ESSM shows levels of inter-rater variability comparable to experienced readers. Finally, we found correlations between the average ESSM at all anatomical locations and other disease activity markers to be moderate to high: faecal calprotectin rs=0.24, CRP rs=0.29, stool frequency rs=0.49, rectal bleeding rs=0.43 and physician global assessment rs=0.47 (Tab. 1). Conclusion Here, we introduced the ESSM, a fully-automated AI-based scoring system that enables accurate, objective and localised assessment of disease severity in UC. In brief, we show that the ESSM compares well with central reading (at the colon section level) and has clinical relevance when compared to other markers of disease activity. This tentatively suggests that the ESSM has the potential to augment the current way of assessing disease severity, both in clinical trials and everyday clinical practice.