Clinical Remission Disease Research Articles

GPx1 deficiency confers increased susceptibility to ferroptosis in macrophages from individuals with active Crohn’s disease

Intestinal cell death is a defining feature of Crohn’s disease (CD), a major form of inflammatory bowel disease. The focus on this aspect of enteric inflammation has mainly been on epithelial cells, while other cell types such as stromal and myeloid cells have received less attention. Hypothesising that decreased macrophage viability in an oxidative environment could be a contributing factor to the pathophysiology of CD, we found that monocyte-derived macrophages from individuals with active CD (but not those in clinical disease remission) have increased sensitivity to cell death induced by H2O2. Molecular biology and pharmacological studies ruled out apoptosis and necroptosis, while increased lipid peroxidation and surface expression of the transferrin receptor implicated ferroptosis as the mechanism of the H2O2-induced cell death: this was supported by suppression of H2O2-cytotoxicity by liproxstatin-1, a pharmacological inhibitor of ferroptosis. Selenoproteins are important antioxidants, and selenium deficiency can be a feature of CD. Despite normal dietary intake of selenium, monocyte-derived macrophages and intestinal macrophages in individuals with CD had decreased protein and/or mRNA expression of the selenoprotein, glutathione peroxidase (GPx)-1. Knockdown of GPx1 in macrophages from healthy volunteers resulted in increased H2O2-induced cell death reminiscent of that observed with macrophages from CD. In summary, monocyte-derived macrophages from individuals with CD have increased susceptibility to H2O2-induced ferroptosis cell death, that may be facilitated, at least in part, by reduced expression of the antioxidant GPx1. We suggest that reduced GPx1 in monocytes recruited to the gut and intestinal macrophages renders these cells vulnerable to reactive oxygen species-evoked ferroptosis cell death and that unraveling the participation of this pathway in Crohn’s disease may reveal novel therapeutic approaches to this chronic condition.

Pro-motility Preparation Protocol May Reduce the Rates of Failed Patency Capsule Among Patients with Crohn’s Disease in Clinical Remission

BackgroundPatency capsule (PC) ingestion is commonly used to minimize capsule retention in high-risk patients with Crohn’s disease (CD). However, false-positive rates remain high, precluding the use of video capsule endoscopy (VCE). We aimed to compare the efficacy of two preparation protocols in reducing failed PC rates in patients with CD.MethodsThis bi-center retrospective case–control study included adult patients with small-bowel CD in clinical remission who underwent PC ingestion. The pro-motility group followed a low-residue diet, then a clear fluid diet, and took bisacodyl after ingestion, while the control group followed only a clear fluid diet. The primary outcome was failed PC, defined as the absence of PC excretion or presence on abdominal X-ray at 30 h post-ingestion. Multivariable logistic regression was used to identify predictors of failed PC.ResultsAmong 273 patients (83 in the pro-motility group, 190 controls), the pro-motility group was older (median 36 [27–48] vs. 31 [24–43], p = 0.012) and had a lower rate of B2/3 disease phenotype (32.5 vs. 53.1%, p = 0.002) compared to controls. The pro-motility group also had a lower failed PC rate (12.0 vs. 24.7%, p = 0.023). Longer disease duration (adjusted odds ratio (AOR) 1.053, 95% confidence interval (CI) 1.016–1.091, p = 0.005) increased the odds of failed PC, while the pro-motility protocol was protective (AOR 0.438, 95% CI 0.200–0.956, p = 0.038), outweighing the influence of B2/3 disease phenotype (AOR 1.743, 95% CI 0.912–3.332, p = 0.093).ConclusionsThe pro-motility preparation protocol could substantially improve the success rates of the small-bowel patency test in patients with CD undergoing PC ingestion, potentially reducing the risk of capsule retention and associated complications.

P122 EXPLORING CARDIOVASCULAR RISK ENHANCERS IN WOMEN: EYE-OPENING FINDINGS TO RETHINK ASSESSMENT

Background and Objectives. Traditional cardiovascular risk (CVR) stratification does not consider CVR enhancers (CVRE). Women present under-recognized CVR factors that may lead to developing subclinical vascular lesions such as arterial stiffness (AS). AS is associated with long-term cardiovascular events and can be determined by carotid-femoral pulse wave velocity (cf-PWV). Our objective was to determine cf-PWV in women with low 10-years CVR (10yCVR) with a CVRE and to compare them with a control group. Methods. Multicentric cross-sectional study, carried out in 2023 in Argentina. Group-1: women, 18-59 years-old, office-BP <140/90 mmHg, low (<5%) 10-yCVR using WHO's Calculator for Argentina, with a CVRE: history of gestational hypertension/preeclampsia; previous oncological treatment in current complete remission; autoimmune hematological or rheumatic disease in clinical remission; history of abortions/preterm births; early menopause/menarche; anxiety/depression disorder. Patients with cardiovascular event, chronic renal disease, diabetes, chronic hypertension, target organ lesion, 10-yCVR≥5%, and those on antihypertensive, statins, or aspirin treatment were excluded. Group-2: healthy women who attended routine control. Consecutive sampling. Office-BP were obtained with Omron-M3. cf-PWV was measured non-invasively through Aortic. AS was defined if cf-PWV exceeded 95% confidence interval (95%CI) upper limit for healthy Argentine population. Institutional Research Committee's approval and informed consent were obtained. Data was analyzed using SPSS for Windows. Results. Included 199 women: Group-1 (N=119); Group-2 (N=80). No differences were found between groups concerning age, weight, height, body mass index and heart rate. Group-1 showed higher cf-PWV: 6.89±1.08 vs. 5.56±0.65 (p<0.0001) and higher AS frequency: 57.1% vs. 2.5% (p<0.0001). In multivariate analysis only CVRE maintain related with AS (p<0.0001). A sub-analysis was performed excluding subjects with high-normal office-BP (27.6% of sample): 144 women remained, 77 (53.5%) in Group-1 and 67 (46.5%) in Group-2. Central (aortic) systolic-BP was <121 mmHg in all cases. Group-1 showed higher cf-PWV: 6.62±0.88 vs. 5.59±0.62 (p<0.0001) and AS: 51.9% vs. 1.4% (p<0.0001). Conclusions. Women with CVRE showed greater cf-PWV and higher proportion of AS.

Dupilumab responder types and predicting factors in patients with type 2 severe asthma: A real-world cohort study

BackgroundSevere asthma (SA) presents a considerable healthcare challenge despite optimal standard treatment. Dupilumab, which is effective in type 2 (T2) SA patients, demonstrates variable responses, categorizing patients as non-responders, partial responders, or those achieving clinical remission. However, real-world response rates remain underexplored. Additionally, understanding the characteristics of patients achieving clinical remission is crucial for predicting favourable responses to dupilumab. ObjectiveTo investigate responder types and identify predictors of clinical remission and non-response induced by dupilumab in a real-world cohort of SA patients. MethodsWe analyzed retrospective data from SA patients undergoing dupilumab treatment in a study conducted at Franciscus Gasthuis & Vlietland hospital. Data were collected at baseline and at a 12 to 24-months follow-up (T = 12). Response rates were evaluated at T = 12. Predictors of non-response and clinical remission were investigated using multivariate logistic regression analysis with a stepwise forward variable selection approach. ResultsAmong the 175 patients screened, 136 met the inclusion criteria. At T = 12, 31.6 % achieved clinical remission, 47.1 % were partial responders and 21.3 % were non-responders. Predictors associated with clinical remission included high baseline blood eosinophil counts (BEC) and male sex. Conversely, younger age at baseline, low baseline total immunoglobin E (IgE) and low baseline fractional exhaled nitric oxide (FeNO) levels were identified as predictors of non-response. ConclusionsDupilumab results in clinical disease remission in one-third of the treated patients. Clinical remission is predicted by high BEC and male sex, whereas low total IgE, low FeNO and younger age indicate a lower likelihood of response.

Influence of multidisciplinary team care with abundant nurse staffing on patient-reported outcomes among patients with inflammatory bowel disease in clinical remission

BackgroundPatients with inflammatory bowel disease (IBD) experience difficulties in daily life and demanding self-care needs. The goal of our support for patients is to ease their difficulties and improve their belief in their capacity to self-manage their disease (self-efficacy), by increasing their ability for self-care. The nurse’s contribution is vital in empowering patients and supporting them to better manage their disease. There is evidence that higher nurse staffing levels are associated with better patient outcomes in acute care settings, but little is known about the outpatient setting. The objective of this study was to explore the impact of multidisciplinary team care with abundant nurse staffing levels on patient-reported outcome measures (PROMs) among patients with IBD, encompassing Crohn’s disease (CD) and ulcerative colitis (UC), in clinical remission.MethodsPatients with IBD in clinical remission were included because disease activity influences the patient’s subjective evaluation. A total of 499 valid responses from two different sources were analyzed: 318 from a specialized IBD clinic with abundant nurse staffing and a multidisciplinary care team (UC: 83, CD: 235) and 181 from an online survey panel (UC: 109, CD: 72). The IBD Self-Efficacy Scale (IBD-SES) and the difficulty of life scale (DLS) were used as disease-specific PROMs.ResultsIn two multiple regression models adjusted by background characteristics (age, sex, diagnosis [UC/CD], employment status, use of biologics, and disease duration) using the IBD-SES or DLS as a dependent variable, the responses from clinic patients showed a more favorable score (higher self-efficacy or lower difficulty) than the online responses.ConclusionsMultidisciplinary team care with abundant nurse staffing may improve self-efficacy and ease difficulties of life among patients with IBD in clinical remission. These results could help bring attention to nurse staffing in an outpatient setting, which has previously been overlooked, and be the first to provide evidence of its importance in encouraging enhanced staffing levels.

A228 RISANKIZUMAB - DRUG INDUCED LIVER INJURY; A CASE REPORT

Abstract Background Risankizumab is a humanized monoclonal antibody to IL-23. It was initially used in the treatment of plaque psoriasis with recent approval to extend use to treat moderate to severe Crohn’s disease with evidence of endoscopic healing and clinical remission of disease. In the drugs safety manual, it has been reported to have transient liver enzyme elevation that is asymptomatic and not to a degree requiring drug discontinuation. No reported data on steatohepatitis. In this article we describe a 28 year old female, who had no evidence of liver disease in the past who underwent treatment with Risankizumab and within several months developed evidence of steatohepatitis with radiological evidence of significant hepatomegaly. Aims Case report details Drug induced liver injury to Risankizumab. Methods Case Report Results Drug induced liver injury with elevated liver enzyme levels and liver biopsy showing drug related liver changes likely in the setting of Risankizumab use. Conclusions Risankizumab is a newly approved drug in the setting of Crohn's disease, although described in the drug assessment report that it may cause transient hepatitis or eleveted liver enzymes in the setting of lower drug dose for Psoriasis use, the higher drug level used in the setting of Crohn's disease has not been formally evaluated and no previous known case reports of Drug induced Liver Injury to Risankizumab causing severe steatohepatitis Funding Agencies None

P989 Switching from intravenous to subcutaneous vedolizumab in patients with inflammatory bowel disease in clinical remission: a multicenter study from GETECCU

Abstract Background Despite the established use of intravenous (IV) vedolizumab for treating inflammatory bowel disease (IBD), there's growing interest in exploring the advantages of the novel subcutaneous (SC) administration route. However, comprehensive real-world evidence regarding the extended safety and effectiveness of this approach remains scarce. The aim of the study was to evaluate the effectiveness and safety of vedolizumab SC among IBD patients in clinical remission. Methods Multicenter, observational, retrospective study. IBD patients on IV vedolizumab treatment across 24 Spanish hospitals who were in clinical remission were given the option to switch to SC injections or continue with IV treatment. Data encompassing clinical disease activity (assessed through partial Mayo score, and Harvey-Bradshaw Index), biochemical markers (C-reactive protein and fecal calprotectin), adverse events and treatment persistence were retrospectively gathered from prospectively maintained clinical records at baseline, and at weeks 12, 24, and 48. Non-parametric tests were used for comparisons and Kaplan-Meier for survival. Results We identified 166 patients, with 19 excluded due to not being in clinical remission and 8 excluded due to absence of follow-up data, resulting in a final inclusion of 139 patients for analysis. Of these, 36 (25.9%) remained on IV vedolizumab, while 103 (74.1%) switched to SC vedolizumab. Both groups exhibited comparable demographic characteristics including age, gender, disease type, disease duration and extension, previous therapy, presence of extra intestinal manifestations and comorbidities (Table 1). However, there were differences in Crohn’s disease behavior among groups (p=0.013). There were not significant differences in clinical, biochemical and fecal calprotectin remission at week 12, 24 and 48 neither in the overall cohort nor assessing Crohn’s disease or ulcerative colitis separately (Figure 1). At the end of follow-up, median duration 47 weeks (29-49), persistence on the same formulation was 85%,1 (2.8%) patient on IV and 4 (3.9%) on SC withdrew the drug (p=0.810), 5 (4.8%) switched back to IV from SC. Adverse events were reported in 1 (2.8%) IV vs 11 (10.7%) SC vedolizumab (p=0.292), most of them being mild skin reactions to SC injection 3 (2.9%). Conclusion In our study we found that transitioning from IV to SC vedolizumab in patients with IBD in remission showed comparable effectiveness in maintaining disease remission. Switching to SC formulation appears safe with no new safety signals identified and most adverse events being mild.

Dietary Perceptions among Patients with Crohn’s Disease in Clinical Remission: Comparison with an Era Preceding the Availability of Biologic Therapy

Introduction: Dietary temperance significantly affects the quality of life of patients with Crohn’s disease (CD) and remains a major concern. However, perceptions of diet in remission may have changed from the era when treatment options were limited. Therefore, we compared the dietary perceptions and treatment of patients with CD in remission with previously published data from the time biologic therapy was not introduced. Methods: We compared the data of 254 patients with CD in remission who completed a questionnaire survey in 2022 with those of 76 patients with CD in remission collected in 2003, when biologics were not used for maintenance therapy in Japan. Remission was defined as a CD activity index of 150 or less in both studies. Perceptions of diet (degree of eating whatever one likes) were assessed using single-item nominal scale responses. Results: The percentage of patients receiving enteral nutrition therapy had decreased (past vs. present: 43.4 vs. 12.6%), while the proportion of patients receiving biologic therapy increased (0 vs. 88.6%, respectively). The percentages of patients who responded “not at all,” “sometimes,” and “mostly” when asked if they could eat whatever they liked had changed, respectively, from 9.2%, 46.1%, and 44.7% in the past to 4.3%, 25.2%, and 70.5% in the present. Conclusion: The proportion of those who ate whatever they liked and the mean body mass index increased in comparison with the corresponding values 20 years ago. With the advent of biologic therapies, the number of patients with CD who can enjoy eating has increased.

Associations between dietary inflammatory index, gut microbiota, inflammation, and permeability in patients with inflammatory Bowel disease in clinical remission

Associations between dietary inflammatory index, gut microbiota, inflammation, and permeability in patients with inflammatory Bowel disease in clinical remission

Adherence to the Mediterranean Diet Is Associated with Decreased Fecal Calprotectin Levels in Children with Crohn's Disease in Clinical Remission under Biological Therapy.

Adherence to the Mediterranean diet (MD) was shown to be associated with decreased disease activity in adult patients with Crohn's disease (CD). Nevertheless, data on its association with fecal calprotectin (FC), particularly in children, remain limited. This study aimed to assess the association between adherence to the MD and FC as an indicator of mucosal healing in patients who are predominantly in remission while undergoing biological therapy. This was a cross-sectional study among children with CD. Adherence to MD was evaluated using both the KIDMED questionnaire and a food frequency questionnaire (FFQ). Israeli Mediterranean Diet Adherence Screener (I-MEDAS) score was calculated, and FC samples were obtained. Of 103 eligible patients, 99 were included (mean age 14.3 ± 2.6 years; 38.4% females); 88% were in clinical remission, and 30% presented with elevated FC. The mean KIDMED score was higher among patients who had FC <200 μg/g compared to patients with FC >200 μg/g (5.48 ± 2.58 vs. 4.37 ± 2.47, respectively; p = 0.04). A moderate correlation between the KIDMED score and the I-MEDAS score was observed (r = 0.46; p = 0.001). In a multivariate regression analysis, adherence to MD was associated with decreased calprotectin levels, OR 0.75 [95% CI: 0.6-0.95], p = 0.019. Vegetable consumption was found to be inversely associated with elevated FC (0.9 portion/day [0.3-2.9] in FC >200 μg/g vs. 2.2 portions/day [0.87-3.82] in FC <200 μg/g; p = 0.049). In children with CD who are mostly in clinical remission under biological therapy, high adherence to MD is associated with decreased FC levels. Encouraging vegetable consumption, especially during remission, may benefit these patients.

Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease

ObjectiveDeep remission defined by clinical-biomarker remission and mucosal healing has emerged as a new therapeutic target in inflammatory bowel disease. The aim of this study was to define an optimal cut-off concentration for infliximab and adalimumab during maintenance therapy associated with deep remission. The secondary objective, was to evaluate the influence of variables on anti tumor necrosis factor-alpha concentrations and deep remission. MethodRetrospective study including 120 and 122 patients inflammatory bowel disease diagnosed who received maintenance therapy with infliximab and adalimumab. Biomarker remission was considered by C-reactive protein < 5 mg/L and fecal calprotectin < 100 µg/g. Crohn's disease clinical remission was defined by a Harvey Bradshaw score < 5 and mucosal healing by a simple endoscopic score for Crohn's disease< 3. In ulcerative colitis, it was defined as a Mayo total score < 3 and Mayo endoscopic subscore < 2. Receiver operating characteristic test was performed to determine drug concentration thresholds associated with deep remission. Anti tumor necrosis factor-alpha concentrations were classified into quartiles. X2 and Kruskal-Wallis test were used to compare discrete and continuous variables between quartile groups. Multivariate logistic regression was performed to identify patient characteristics and serological facto C-reactive protein rs associated with deep remission. ResultsAnti tumor necrosis factor-alpha concentrations were higher in patients with deep remission, in infliximab (4.4, interquartile range: 3.3-6.5 vs 2.3, interquartile range: 1.1-4.2 µg/mL, P < 0.005) and adalimumab (6.3, interquartile range: 4.2-8.2 vs 3.9, interquartile range: 2.4-5.5 µg/mL, P < 0.005). A Receiver operating characteristic test identified a concentration threshold of 3.1 µg/mL in infliximab (area under the Receiver operating characteristic test curve, 0.72) and 6.3 µg/mL in adalimumab (area under receiver operating characteristic test curve, 0.75) associated with deep remission. Factors associated with the highest quartiles of serum infliximab concentration were: elevated body mass index, absence of previous inflammatory bowel disease-surgery, C-reactive protein < 5 mg/L, and fecal calprotectin < 100 µg/g. In adalimumab, higher quartiles were related to concomitant immunosuppressants, low body mass index, absence of previous inflammatory bowel disease-surgery, and C-reactive protein < 5 mg/L and fecal calprotectin < 100 µg/g. Multivariate regression identified fecal calprotectin < 100 µg/g, C-reactive protein < 5 mg/L, infliximab > 3.1 µg/mL and adalimumab concentrations > 6.3 µg/mL as factors significantly associated with deep remission. ConclusionsTrough infliximab and adalimumab concentrations, C-reactive protein < 5 mg/L and fecal calprotectin < 100 µg/g are associated with deep remission during maintenance therapy. Cutoff point of 3.1 and 6.3 g/mL for infliximab and adalimumab respectively, were identified as deep remission predictors.

Serum leucine-rich alpha-2 glycoprotein levels for predicting active ultrasonographic findings in intestinal lesions of patients with Crohn's disease in clinical remission.

This study aimed to investigate the cutoff value of leucine-rich alpha-2 glycoprotein (LRG) in predicting active intestinal ultrasonography (IUS) findings in patients with Crohn's disease (CD) in clinical remission. Data were retrospectively collected from patients with CD evaluated using LRG and undergoing IUS from September 2020 to August 2022. Patients with a Harvey-Bradshaw Index of ≤4 were included and those who underwent intestinal resection were excluded. Bowel wall thickness and stratification and blood flow signal using superb microvascular imaging (SMI) were used to assess ultrasonography findings. SMI signals were categorized into 4 grades following the Limberg score. Receiver operating characteristic curves were constructed and the area under the curve was calculated to determine the LRG cutoff values for predicting active IUS findings and were compared with those of C-reactive protein. This study included 213 patients. The LRG cutoff values to predict active bowel wall thickness, loss of bowel wall stratification, and SMI of ≥1, ≥2, and 3 were 14.6 μg/mL, 14.6 μg/mL, 14.6 μg/mL, 14.6 μg/mL, and 16.9 μg/mL, respectively, with significantly higher areas under the curve in SMI of ≥1 and 3 than in C-reactive protein. The best LRG cutoff value for predicting active IUS findings was 14.6 μg/mL in patients with CD in clinical remission, suggesting that LRG is better than C-reactive protein for detecting active IUS findings in CD.

N15 Influence of abundant nurse staffing on patient-reported outcomes among patients with inflammatory bowel disease in clinical remission

Abstract Background There is evidence that a higher number of nurses is associated with better patient outcomes in acute care settings, but little is known in outpatient settings. Patients with inflammatory bowel disease (IBD) are largely treated in outpatient settings and sometimes face difficulties due to their disease or treatment. Through the experience of living with their disease and managing it well, their self-efficacy related to IBD management would improve. Health professionals play important roles in empowering patients and supporting them to be able to manage their disease conditions well. The aim of this study is to explore the impact of adequate support with abundant nurse staffing on self-efficacy and difficulties of life among patients with IBD in clinical remission. Methods This is a cross-sectional questionnaire survey, using secondary analysis of a previously reported larger study. Data of a total of 499 patients with IBD in clinical remission, 318 from a specialized IBD clinic (UC: 83, CD: 235) and 181 online (UC: 109, CD: 72), was used for this study. The clinic has 10 full-time staffs (2 physicians, 7 nurses, 1 pharmacist) and 3 part-time staffs (2 doctors, 1 counselor) for approximately 30 outpatients visiting the clinic per day. This number shows the clinic is considerably abundant in nurse staffing compared to the Japanese standard of 1 nurse per 30 outpatients set by the Medical Care Law. The IBD-Self-Efficacy Scale (IBD-SES) and difficulty of life scale (DLS) were used as disease specific patient reported outcome measures. Multiple regression analysis was conducted in order to assess the extent of influence by the difference of facility after adjusting potential effects of confounders. Results All multi regression models included following confounders; age, sex, disease, job status, use of biologic, and disease duration. In IBD-SES, the subscales except for the subscale “managing medical care” showed significantly higher self-efficacy scores in patients who were recruited from the specialized clinic than those from online. As for DLS, all subscales and the total score showed significantly lower difficulty scores in patients who were recruited from the clinic. Conclusion Our results suggest that abundant nurse staffing influences favorably on self-efficacy and difficulties of life among patients with IBD in clinical remission.

Heart rate recovery in patients with inflammatory bowel disease in clinical remission

Heart rate recovery in patients with inflammatory bowel disease in clinical remission

Inflammatory Bowel Disease Patients' Acceptance for Switching from Intravenous Infliximab or Vedolizumab to Subcutaneous Formulation: The Nancy Experience.

Subcutaneous infliximab and vedolizumab formulations have been developed for maintenance therapy in inflammatory bowel disease. The objective of this study was to explore the inflammatory bowel disease patient's acceptance for switching from intravenous infliximab or vedolizumab to subcutaneous, as well as to describe the causes of refusal or, conversely, the factors associated with acceptance. Patients were prospectively recruited between June 2021 and March 2022 during their infusion of infliximab or vedolizumab in the Medical Day Hospital of Nancy University Hospital. Adult patients with an established diagnosis of inflammatory bowel disease in clinical remission were eligible for inclusion in this study if they had been treated with intravenous infliximab or vedolizumab for at least six months. One hundred and thirty patients were included in this study. Thirty-six patients (27.7%) received vedolizumab and ninety-four patients (72.3%) received infliximab. Median duration of treatment at inclusion was 7.0 years [3.0-11.0]. In this cohort, 77.7% of patients accepted the switch from intravenous infliximab or vedolizumab to subcutaneous. The main reasons for patient's refusal for switching from intravenous to subcutaneous formulation were fear of loss of efficacy, a more spaced-out medical follow-up, increased frequency of administration, and self-administered injection. A short duration of treatment was associated with a high switch acceptance rate (odd ratio (OR) (95% confidence interval (CI)) = 0.9 (0.8-0.9); p = 0.0002). A large majority of the patients included accepted the switch of their treatment with infliximab or vedolizumab from the intravenous form to the subcutaneous form. This study identified one predictor influencing the acceptance rate in inflammatory bowel disease population: short treatment duration. Subcutaneous infliximab and vedolizumab hold potential for greater patient flexibility by self-administration, reducing travel and hospital attendance for infusion.

Fecal S100A12 is associated with future hospitalization and step-up of medical treatment in patients with Crohn's disease in clinical remission: a pilot study.

Background/Aims Fecal S100A12 (FS) and serum S100A12 (SS) have been reported as novel biomarkers that accurately reflect intestinal inflammation. We evaluated if FS and SS in comparison to fecal calprotectin (FC) are associated with poor future outcomes in clinically quiescent Crohn’s disease (CD) patients.Methods We prospectively enrolled 49 CD patients in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150 for the past 6 months). Patients were followed for a median period of 4.4 years (interquartile range [IQR], 4.3–4.5). The following outcomes were evaluated: clinical relapse, CD-related hospitalization, step-up of medical treatment, and CD-related intestinal resection. Cox proportional-hazard regression model was constructed to assess the association of baseline markers with time-to-event outcomes.Results The median levels of baseline FS, FC, and SS were 0.042 mg/kg (IQR, 0.005–0.179), 486.8 mg/kg (IQR, 203.5–886.8) and 1,398.2 ng/mL (IQR, 791.8–2,759.9), respectively. FS correlated with FC (r = 0.689), erythrocyte sedimentation rate (r = 0.524), C-reactive protein (r = 0.499), and albumin (r = –0.446), but not with CDAI (r = 0.045). Interestingly, increased FS (top quartile) was associated with a 4.9-fold increased rate of future CD-related hospitalization (P= 0.009) and a 2.8-fold increased rate of step-up of medical treatment (P= 0.032), whereas increased FC and SS were not. These findings remained significant after adjusting for age, sex, disease duration, current smoking, C-reactive protein, serum albumin, CDAI, and FC, individually.Conclusions In this pilot study, increased FS and not FC or SS, was significantly associated with increased rates of future CD-related hospitalization and step-up of medical treatment among CD patients in clinical remission.

Health-Related Quality of Life in Patients with Inflammatory Bowel Disease in Clinical Remission: What Should We Look For?

Background and Objectives: Inflammatory bowel diseases (IBD) are chronic conditions with an unpredictable evolution that can have a negative impact on patients’ quality of life (QoL). Even though patients in remission have a better QoL compared to patients with active disease, they still have a lower QoL compared to healthy people. The aim of this study is to identify the factors that are associated with a lower QoL in patients with IBD in clinical remission, in a tertiary IBD center in Romania. Materials and Methods: Ninety-seven adult patients with a current diagnosis of IBD for over 3 months who were in clinical remission were enrolled in this study. Pregnant women, patients with ostomy, perianal disease, extraintestinal manifestations or other significant comorbidities were excluded. Out of the 97 patients, 63.9% were men. The median age was 39 years (IQR 29–47), and the median disease duration was 5 years (IQR 2–10). Disease activity was assessed using the SCCAI score for ulcerative colitis and HBI score for Crohn’s disease. Remission was defined for SCCAI score ≤ 1 and HBI score ≤ 4. The health-related quality of life (HR-QoL) was assessed using the IBDQ32 score. FACIT-Fatigue was used to evaluate the level of fatigue. Patients with symptoms of anxiety or depression were identified with the HADS score. Symptoms of anxiety were considered when HADS-A >7 points and symptoms of depression when HADS-D >7 points. Results: Sixty-five patients (67%) were diagnosed with CD and the remaining 32 (33%) with UC. Ninety-three patients (95.9%) were on biological therapy. The mean IBDQ score (total score) was 190.54 points (SD +/− 8.2). The mean FACIT Fatigue score was 42.5 (SD +/− 8.2), with 6.2% of patients suffering from severe fatigue (FACIT Fatigue < 30 points). A total of 33% of patients had symptoms of anxiety and 16.5% of depression. Exposure to more than one biologic therapy (p = 0.02), fatigue (p < 0.001) and symptoms of anxiety (p < 0.001) were associated with a lower HR-QoL in the multivariate analysis. Female patients, patients with Crohn’s disease, patients with anemia and patients with symptoms of depression also had a lower HR-QoL, but this did not reach statistical significance in our study. Conclusions: Exposure to a higher number of biological agents (patients that switched multiple biologics), the presence of fatigue and symptoms of anxiety impair the HR-QoL of patients with IBD in clinical remission. Further studies should assess in a prospective manner whether early identification of these factors with prompt clinical interventions could lead to a better HR-QoL in these patients.

P534 Effectiveness and safety of Adalimumab switch from originator to biosimilar in patients with inflammatory bowel disease in clinical remission

Abstract Background Multiple adalimumab (ADA) biosimilars are now available since they were first commercialized in 2019 after having proved their safety and effectiveness in rheumatoid diseases. However, real data in inflammatory bowel disease (IBD) remain scarce. The main aim was to evaluate the remission rates after switching from ADA originator (Humira) to biosimilar (Hyrimoz) in a cohort of patients in remission at time of inclusion as well as to describe any safety issues. Methods We performed a prospective, observational cohort in a tertiary IBD referral centre. All patients on Humira who were in clinical remission (defined as Harvey-Bradshaw score ≤4 or partial Mayo score ≤2) +/- biological remission (faecal calprotectin &amp;lt;250 μg/gr and C-reactive protein [CRP] &amp;lt;5gr/L) +/- endoscopic/radiologic remission at time of switch were included and followed-up for at least 9 months. Data on IBD phenotype, CRP, ADA drug and antibody levels and faecal calprotectin were collected. Results A total of 40 patients were included, 53.7% (22) men. Median follow-up 10.6 months (IQR 10–11.1). Regarding IBD type, 85.4% (35) suffered from Crohn′s disease (CD) and 14.6% (6) from ulcerative colitis (UC). Table 1 shows the baseline characteristics of patients. Prior to switch, adalimumab levels were 7.7 mg/mL (5.9–11.2), CRP 0.4 (0–1.7) gr/L and faecal calprotectin 140 μg/gr (69–180). One patient stopped the drug (2.5%) as per personal reasons and 5% (2) flared during the follow-up but no drug cessation was needed. At the end of follow-up 94.9% (37) patients remained in clinical remission. No severe adverse events were reported. Statistical differences were found in ADA levels prior and after switching (7.7 vs 5.9 mg/mL, p=0.001), CRP levels (0.4 vs 0.7 g/L; p=0.016) and albumin levels (4.4 vs 4.6 g/L, p=0.015). Conclusion Switching from Humira to Adalimumab biosimilar appeared to be effective and safe with most patients being in clinical remission at the end of follow-up. Statistical differences were found in adalimumab levels, CRP after switching and albumin, however, the impact of these differences was not noticeable.

P100 Serum inflammatory protein profiling to corroborate selection of therapy naïve moderate-to-severe pediatric Crohn’s disease patients eligible for first-line infliximab treatment

Abstract Background Early intervention with biologic therapy, especially with anti-Tumor Necrosis Factor-a, is very effective and now more commonly used to prevent disease progression and complications in Crohn’s disease (CD). However, a rational approach to decide which patient should be treated First-line Infliximab (FL-IFX) is lacking. In this study, using serum from a randomized control trial, we assessed how changes in immune profiles prior to therapy and after the first standardized induction treatment with either FL-IFX or conventional treatment (CONV) related to maintaining disease remission at week 52. Methods Serum samples from therapy naive moderate to severe CD patients from the TISKIDS study1 were used at time of diagnosis and at 10–14 weeks after induction therapy with FL-IFX (n=48) and CONV (n=43). FL-IFX consisted of 5 IFX infusions (5 mg/kg) combined with azathioprine (AZA) maintenance. CONV consisted of induction therapy with Exclusive Enteral Nutrition or oral prednisolone combined with AZA maintenance. Concentrations of 92 inflammatory proteins were determined with Olink Proteomics®. Significant differences in mean protein NPX after FDR adjustment with log2fold &amp;gt; 0.5 were considered meaningful. Results After 10–14 weeks of induction therapy, FL-IFX suppressed a larger number inflammatory proteins and induced stronger suppression compared to CONV. Of the 30 significantly modulated FL-IFX target proteins 18 were differentially regulated by FL-IFX only. Hierarchical clustering of patients based on their baseline profiles of the 30 IFX-modulated proteins revealed 2 patient clusters, a CD-hi cluster with significantly higher baseline clinical disease activity, CRP and blood neutrophil concentrations compared to the CD-lo cluster. The CD-hi cluster had an increased abundance of 23/30 proteins amongst which Oncostatin-M, TNFSF14, HGF and TGF-alpha compared to the CD-lo cluster (Figure 1A). Of the CD-lo patients treated with FL-IFX, 58% reached clinical disease remission without treatment escalation at week 52, while this was only 24% for CD-hi patients treated with FL-IFX. Only 20% of the CD-lo patients treated with CONV reached remission while this was only 6% for the CONV treated patients in the CD-hi group (Figure 1B). Strikingly, similar clustering using the immune profiles after 10–14 weeks induction therapy did not predict remission at week 52. Conclusion FL-IFX achieves stronger reduction and modulates more inflammatory serum immune protein concentrations than CONV. Stratification of patients according to profiles of IFX-modulated proteins prior to therapy identifies patients with a lower chance of reaching clinical remission without treatment escalation at week 52. Reference 1. Jongsma MME et al. Gut. 2020 Dec; DOI:10.1136/ PMID:33384335

Utility of interval kidney biopsy in ANCA-associated vasculitis.

ObjectivesANCA-associated vasculitis (AAV) is a rare autoimmune disorder that commonly involves the kidney. Early identification of kidney involvement, assessing treatment-response and predicting outcome are important clinical challenges. Here, we assessed the potential utility of interval kidney biopsy in AAV.MethodsIn a tertiary referral centre with a dedicated vasculitis service, we identified patients with AAV who had undergone interval kidney biopsy, defined as a repeat kidney biopsy (following an initial biopsy showing active AAV) undertaken to determine the histological response in the kidney following induction immunosuppression. We analysed biochemical, histological and outcome data, including times to kidney failure and death for all patients.ResultsWe identified 57 patients with AAV who underwent at least one interval kidney biopsy (59 interval biopsies in total; median time to interval biopsy ∼130 days). Of the 59 interval biopsies performed, 24 (41%) patients had clinically suspected active disease at time of biopsy which was confirmed histologically in only 42% of cases; 35 (59%) patients were in clinical disease-remission, and this was correct in 97% of cases. The clinician’s impression was incorrect in one in four patients. Hematuria at interval biopsy did not correlate with histological activity. Interval biopsy showed fewer acute lesions and more chronic damage compared with initial biopsy and led to immunosuppressive treatment-change in 75% (44/59) of patients. Clinical risk prediction tools tended to operate better using interval biopsy data.ConclusionInterval kidney biopsy is useful for determining treatment-response and subsequent disease management in AAV. It may provide better prognostic information than initial kidney biopsy and should be considered for inclusion into future clinical trials and treatment protocols for patients with AAV.