Disease Patients In Clinical Remission Research Articles

Effectiveness and Safety of Switching from Intravenous to Subcutaneous Vedolizumab Formulation in Inflammatory Bowel Disease Patients in Clinical Remission.

Subcutaneous vedolizumab formulation has been shown to be as effective and safe as the intravenous one in randomized control trials. Real-life data are limited especially for patients receiving long-term intravenous therapy. This study aimed to evaluate the safety and effectiveness of switching from intravenous to subcutaneous vedolizumab in a large cohort of patients with stable clinical remission. In this prospective cohort study, we enrolled consecutive patients attending our center between September 2021 and April 2022. The baseline demographic characteristics, 12- and 24-weeks follow-up clinical activity, C-reactive protein levels, and adverse events were recorded. The primary endpoint was to assess combined steroid-free clinical remission plus biochemical remission 24-week after the switch. 93 patients (43 Crohn's disease, 50 ulcerative colitis), switched to subcutaneous vedolizumab after a median duration of intravenous treatment of 36 months [IQR 16-52]. At baseline, 80 patients (86%) had a combined remission. At 24-week, 89.2% (n=74) maintained combined steroid-free clinical remission plus biochemical remission. 25 adverse events were reported, mostly SARS-CoV-2 infections and injection site reactions, with a further four recurrence episodes. Twelve patients (12.9%) discontinued subcutaneous administration and restarted intravenous vedolizumab. Switching from intravenous to subcutaneous vedolizumab can be considered effective and safe for maintaining remission in patients with inflammatory bowel disease. In addition, this might reduce healthcare costs. However, large-scale real-life studies with long-term follow-up are necessary.

Altered gut microbiota and gut permeability in Crohn’s disease patients in clinical remission

Rationale: Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD), which is associated with alterations in gut microbiota (GM) and increased gut permeability (GP). The aim of this study was to evaluate GM composition and GP in CD patients in remission comparing to healthy subjects.

Differences between gut microbiota profile and gut permeability in ulcerative colitis vs. Crohn’s disease patients in clinical remission

Rationale: Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and Ulcerative Colitis (UC), are chronic inflammatory diseases associated with alterations gut microbiota (GM) and gut permeability (GP). We aimed to investigate the differences in GM and GP profile in patients with IBD.

Poor Drug Sustainability in Inflammatory Bowel Disease Patients in Clinical Remission on Thiopurine Monotherapy.

Immunomodulator monotherapy is an important component in the treatment of inflammatory bowel disease (IBD). However, there is conflicting literature about thiopurines maintaining long-term remission in patients with active IBD. To determine the durable clinical remission rate in adults with Crohn's disease (CD) or ulcerative colitis (UC) on thiopurine monotherapy over 5years. We performed a retrospective analysis of adult patients identified at McGill University Health Centre from 2009 to 2012. We included IBD patients who initiated thiopurine monotherapy and were in remission for at least 3months (Harvey-Bradshaw Index (HBI) < 5 points for CD and partial Mayo Score (pMS) < 2 points in UC). The primary endpoint was sustained clinical remission on thiopurines during a 5-year follow-up. This included patients who had not relapsed or discontinued the drug due to side effects. The secondary endpoint was clinical relapse over the follow-up period, which was defined as HBI > 5 in CD and pMS > 2 in UC. There were 148 patients included in the study (100 CD; 48 UC). At 5years, 23% (34/148) patients remained in clinical remission on thiopurine monotherapy (25 CD and 9 UC patients). Thirty-three percent (33/100) of CD and 46% (22/48) of UC patients relapsed while on thiopurines. There was no difference in relapse rates between CD and UC patients. Eighty-four percent (42/50) of patients with CD with side effects and all UC (17/17) patients who experienced side effects discontinued the drug. This analysis demonstrates that there is poor sustainability of clinical remission in IBD patients on thiopurine monotherapy given that a high proportion of patients discontinue thiopurines due to either relapse or side effects.

Proactive TDM for Crohn's Disease Patients in Clinical Remission Under Anti-TNF Treatment: Current State of Evidence.

Proactive TDM for Crohn's Disease Patients in Clinical Remission Under Anti-TNF Treatment: Current State of Evidence.

P545 Deep remission assessed by endoscopy, magnetic resonance or intestinal ultrasound, in refractory Crohn’s disease patients in clinical remission with ustekinumab: a real-life single-centre experience

Abstract Background Current therapeutic goals in Crohn’s disease (CD) include not only the mere absence of symptoms but also the objective resolution of macroscopic lesions, so-called deep remission (DR), which has been related to better outcomes. DR is usually acknowledged by endoscopy, although magnetic resonance (MR) or intestinal ultrasound (IUS) are also reliable, provide extramucosal information and may be more appropriate in certain clinical scenarios. Data regarding the achievement of DR with ustekinumab in real-life clinical practice is still scarce. Methods Retrospective cohort study carried out in a tertiary hospital between April 2017 and April 2019 including patients who had clinically active CD (Harvey–Bradshaw index [HBI] ≥ 4) objectively assessed by either endoscopy, MR or IUS; received intravenous induction with ustekinumab, had achieved clinical remission and had treatment response assessed by either endoscopy, MR or IUS. DR was defined by SES-CD 0–3 or Rutgeerts index i0 if endoscopically assessed, or by complete normalisation of inflammatory parameters on cross-sectional imaging. Endoscopic response was defined by the decrease of SES-CD of 50% compared with baseline. Radiographic response was defined by improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyperenhancement compared with baseline imaging by physician global assessment. Demographics, clinical data and information regarding ustekinumab treatment were collected. Results 90 patients treated with ustekinumab at our centre were analyzed, but only 28 met inclusion criteria (14(50%) female; median age 45 (43–50)) with a median follow-up of 19 (IQR: 15–23) months. All of them had previously failed to antiTNFα and 20 (71%) failed to ≥2 biologics. Treatment response assessment was made by endoscopy (22 cases; 79%) or cross-sectional imaging technique (6 cases; 21%) in a median time of 10 months (IQR: 7–13) from the start of treatment. Deep remission was achieved in 18 (64%) patients. Endoscopic response was achieved in 5 (18%) additional patients. Five (18%) remaining patients obtained no objective response to ustekinumab despite being in clinical remission. Patients who had received prior treatment with ≥2 biologics or those classified as B2 or B3 according to Montreal Classification were less likely to achieve deep remission, although those associations did not reach statistical significance. Conclusion In our experience, a majority of refractory CD patients who achieved clinical remission with ustekinumab also reached deep remission assessed by either endoscopy, MR or IUS.

P378 Mucosal healing is achieved in most of the inflammatory bowel disease patients in clinical remission with vedolizumab: a real-life single-centre experience

Abstract Background Current therapeutic goals in inflammatory bowel disease (IBD) include not only the mere absence of symptoms but also the resolution of endoscopic lesions, so-called mucosal healing (MH), which has been related to better outcomes. Data regarding the achievement of MH with vedolizumab (VDZ) in real-life clinical practice is still scarce. Methods Retrospective cohort study was carried out in a tertiary hospital between January 2015 and April 2019 including patients with a basal colonoscopy showing activity and who achieved clinical remission under treatment with VDZ, defined by partial Mayo score &amp;lt;2 for ulcerative colitis (UC) and Harvey–Bradshaw Index score (HBI) &amp;lt;4 for Crohn’s disease (CD). Surveillance colonoscopy was performed along with the follow-up according to clinical practice. In UC patients, MH was defined as Mayo Endoscopic Subscore (MES) = 0; the endoscopic response was defined by a decrease in MES ≥1 point. In CD, MH was defined by achievement SES-CD = 0–3 or Rutgeerts index i0; the endoscopic response was defined by a decrease of SES-CD of 50% or Rutgeerts index &amp;lt;i2 with at least 1 point of decease compared with baseline. Results In total, 118 patients treated with VDZ were analysed, but only 45 met inclusion criteria with a median follow-up of 21 (IQR: 14–19) months. Surveillance colonoscopy was performed after a median time of 12 months (IQR:9–17) of treatment. MH achieved in 33/45 patients (73%): 17/23 CD patients (74%) and 16/22 UC patients (73%). The endoscopic response was achieved in 9 of the remaining 12 patients: 3/6 CD patients and 6/6 UC patients. Only 3 (7%) of patients included showed no endoscopic benefit at the time of surveillance endoscopy. In multivariate analysis, probability of not achieving MH was 75% in patients previously treated with immunosuppressants (ISS) (HR 0.25, 0.11–0.55 IC95; p = 0.001) and 60% in patients previously treated with anti-TNFα (HR 0.40, 0.18–0.90 95% CI; p = 0.026). Type of IBD, concomitant ISS, corticosteroid use at induction, baseline endoscopy score or duration of disease before VDZ treatment were not associated with the achievement of MH. Conclusion In our experience, most of the patients who achieve clinical remission with VDZ also achieve MH. Refractory patients were less likely to achieve MH despite having achieved clinical remission.

Evolution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission

Abstract Background and aim The biosimilar of infliximab (CT-P13) has been approved for the same indications held by the infliximab reference product (Remicade®); however, there are few clinical data on switching in inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy, safety, bioavailability profile and factors associated with relapse after switching to biosimilar infliximab in IBD patients in clinical remission. Material and method Observational study with IBD patients treated with Remicade® for at least 6 months and in clinical remission for at least 3 months who switched to infliximab biosimilar. The incidence of relapse, adverse effects and possible changes in drug bioavailability (trough level and antidrug antibodies) were evaluated. Results Thirty six patients were included (63.9% CD) with a mean follow-up of 8.4 months (SD ± 3.5). The 13.9% had clinical relapse. The longer clinical remission time before switching (HR = 0.54, 95% CI = 0.29–0.98, p = 0.04) and detectable infliximab levels at the time of switching (HR = 0.03, 95% CI = 0.001–0.89, p = 0.04) were associated with a lower risk of relapse. No differences were found between infliximab levels at the time of switching and at weeks 8 and 16 (p = 0.94); 8.3% of the patients had some adverse event, requiring the suspension of biosimilar in one patient for severe pneumonia. Conclusion Switching to biosimilar infliximab in a real-life cohort of IBD patients in clinical remission did not have a significant impact on short-term clinical outcomes. The factors associated with relapse were similar to those expected in patients continuing with Remicade®.

P627 Surrogate markers of mucosal healing in Crohn's disease patients in clinical remission under biological/immunomodulator treatment

P627 Surrogate markers of mucosal healing in Crohn's disease patients in clinical remission under biological/immunomodulator treatment

P545 Clinical outcomes following a switch from Remicade® to the biosimilar CT-P13 in inflammatory bowel disease patients in clinical remission: preliminary results

P545 Clinical outcomes following a switch from Remicade® to the biosimilar CT-P13 in inflammatory bowel disease patients in clinical remission: preliminary results

A Disease-Associated Microbial and Metabolomics State in Relatives of Pediatric Inflammatory Bowel Disease Patients.

Background & AimsMicrobes may increase susceptibility to inflammatory bowel disease (IBD) by producing bioactive metabolites that affect immune activity and epithelial function. We undertook a family based study to identify microbial and metabolic features of IBD that may represent a predisease risk state when found in healthy first-degree relatives.MethodsTwenty-one families with pediatric IBD were recruited, comprising 26 Crohn’s disease patients in clinical remission, 10 ulcerative colitis patients in clinical remission, and 54 healthy siblings/parents. Fecal samples were collected for 16S ribosomal RNA gene sequencing, untargeted liquid chromatography–mass spectrometry metabolomics, and calprotectin measurement. Individuals were grouped into microbial and metabolomics states using Dirichlet multinomial models. Multivariate models were used to identify microbes and metabolites associated with these states.ResultsIndividuals were classified into 2 microbial community types. One was associated with IBD but irrespective of disease status, had lower microbial diversity, and characteristic shifts in microbial composition including increased Enterobacteriaceae, consistent with dysbiosis. This microbial community type was associated similarly with IBD and reduced microbial diversity in an independent pediatric cohort. Individuals also clustered bioinformatically into 2 subsets with shared fecal metabolomics signatures. One metabotype was associated with IBD and was characterized by increased bile acids, taurine, and tryptophan. The IBD-associated microbial and metabolomics states were highly correlated, suggesting that they represented an integrated ecosystem. Healthy relatives with the IBD-associated microbial community type had an increased incidence of elevated fecal calprotectin.ConclusionsHealthy first-degree relatives can have dysbiosis associated with an altered intestinal metabolome that may signify a predisease microbial susceptibility state or subclinical inflammation. Longitudinal prospective studies are required to determine whether these individuals have a clinically significant increased risk for developing IBD.

P394. Psychosexual dysfunction in a cohort of Greek inflammatory bowel disease patients in clinical remission: preliminary results

P394. Psychosexual dysfunction in a cohort of Greek inflammatory bowel disease patients in clinical remission: preliminary results

Unrevealed Depression Involves Dysfunctional Coping Strategies in Crohn's Disease Patients in Clinical Remission.

Background and Aims. This study investigated the proportion of CD patients in clinical remission with clinical depression, and coping strategies in those with severe depressive disorders. Materials and Methods. One hundred consecutive CD patients in clinical remission were screened for anxiety and depression by using Hospital Anxiety and Depression Scale and patients with depressive symptoms were further investigated by means of Cognitive Behavioural Assessment 2.0 and Beck Depression Inventory (BDI). Afterwards the coping strategies were assessed through the Brief-COPE questionnaire. Results. Twenty-one patients had anxious symptoms and 16 had depressive symptoms with or without anxiety. Seven of these patients (43.8%) showed significant depressive symptoms. Compared to patients without psychiatric disorders, these patients showed significant lower score in “positive reframing” (p: 0.017) and in “planning” (p: 0.046) and higher score in “use of instrumental social support” (p < 0.001), in “denial” scale (p: 0.001), and in “use of emotional social support” (p: 0.003). Conclusions. Depressed CD patients in clinical remission may have dysfunctional coping strategies, meaning that they may not be able to implement functional strategies to manage at best stress related with their disease.

Therapeutic drug monitoring is predictive of loss of response after de-escalation of infliximab therapy in patients with inflammatory bowel disease in clinical remission

There is no evidence that therapeutic drug monitoring is helpful in patients with inflammatory bowel disease patients in clinical remission with infliximab therapy. Eighty consecutive inflammatory bowel disease patients in clinical remission on infliximab maintenance therapy were included and followed-up for at least one year. Infliximab trough level and antibody to infliximab concentration were measured prior to enrollment. At the time of enrollment, physicians in charge were free to alleviate infliximab therapy. Discrepancies between blind and therapeutic drug monitoring-based adjustments were assessed at the end of the follow-up period. Relapse-free survival was analyzed using univariate and multivariate analyses. The mean infliximab trough level was 3.1 μg/mL. Antibody to infliximab was found in 15 (19%) patients. At the end of the follow-up period, 18 (22.5%) patients experienced a relapse. The 3, 6, 9 and 12-month relapse-free rates were 98%, 87%, 86% and 80%, respectively. In our multivariate analysis, relapse-free survival was negatively associated with discrepancies between therapeutic drug monitoring-based and blind adjustments of infliximab therapy, absence of concomitant immunomodulator, the absence of mucosal healing, prior use of infliximab, infliximab therapy duration>2 years and C-reactive protein levels>5mg/L at the time of enrollment. In patients with inflammatory bowel disease in clinical remission on infliximab therapy, de-escalation of infliximab therapy should be considered based on therapeutic drug monitoring rather than according to symptoms and CRP.

Sa1194 Prospective, Multicenter Capsule Endoscopy Study of Small Bowel Crohn's Disease Patients in Clinical Remission: Long-Term Follow-Up and Correlation With Faecal Lactoferrin and Calprotectin Levels

Background: Histologic assessment is an evolving outcome measure in ulcerative colitis (UC). Many histological indices, including the Geboes score (GS; Figure 1 top panel) and Modified Riley Score (MRS; Figure 1 bottom panel) have been used to grade disease activity and served as endpoints for clinical trials. The operating properties of these indices, including agreement have not been fully evaluated. We assessed interand intra-rater agreement of central readers for histopathological evaluation of UC disease activity.Methods: Five central readers individually evaluated 50 slides of colonic biopsies taken from patients with UC on three separate occasions at least two weeks apart using the GS, MRS and a global rating of severity based on a 100 mm visual analogue scale (VAS). Interand intra-rater agreement was measured using intraclass correlation coefficients (ICC) for each grading system and for components of acute and chronic inflammation. Results: Intra-rater ICCs (95% confidence intervals) for the total GS, MRS and VAS scores were 0.83 (0.78, 0.87), 0.72 (0.65, 0.79) and 0.79 (0.74, 0.85), respectively. Corresponding inter-rater agreement ICCs were 0.57 (0.45, 0.68), 0.49 (0.38, 0.61) and 0.61 (0.51, 0.72) (Table 1). The correlation between each central reader's VAS with GS and MRS descriptors were 0.60 (0.44, 0.76) and 0.63 (0.47, 0.77), respectively. The items with lowest ICC (highest disagreement) were granuloma (0.01), patchiness (0.20), lamina propria fibrosis (0.21), lamina propria eosinophilia (0.26), crypt abscesses (0.32), crypt destruction (0.34), surface epithelium integrity (0.35), and lamina propria neutrophils (0.37). Conclusion: There is substantial to almost perfect intra-rater agreement among histopathologists in the assessment of disease activity in UC. Inter-rater agreement was less satisfactory. The results indicate that a central reader is highly reliable for the assessment of UC histologic disease. However, differences in interpretations of the scores among readers requires further study and standardization in order to determine the optimal instrument for use in UC clinical trials. A Delphi process has been initiated to further characterize the most important sources of disagreement. Table 1. Interand Intra-rater Agreement for Index Components

A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn's disease

BackgroundFaecal calprotectin (FC) is a non-invasive marker of gastrointestinal inflammation. AimTo determine whether higher FC levels in individuals with quiescent Crohn's disease are associated with clinical relapse over the ensuing 12months. MethodsA single centre prospective study was undertaken in Crohn's disease patients in clinical remission. The receiver operating characteristic (ROC) curve for the primary endpoint of clinical relapse by 12months, based on FC at baseline, was calculated. Kaplan–Meier curves of time to relapse were based on the resulting optimal FC cutoff for predicting relapse. ResultsOf 97 patients recruited, 92 were either followed up for 12months without relapsing, or reached the primary endpoint within that period. Of these, 10 (11%) relapsed by 12months. Median FC was lower for non-relapsers, 96μg/g (IQR 39–237), than for relapsers, 414μg/g (IQR 259–590), (p=0.005). The area under the ROC curve to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240μg/g to predict relapse had sensitivity of 80.0% and specificity of 74.4%. Negative predictive value was 96.8% and positive predictive value was 27.6%, FC≥240μg/g was associated with likelihood of relapse by 12-months 12.18 (95%CI 2.55–58.2) times higher than lower values (p=0.002). ConclusionsIn this prospective dataset, FC is a useful tool to help identify quiescent Crohn's disease patients at a low risk of relapse over the ensuing 12months. FC of 240μg/g was the optimal cutoff in this cohort.

Probe-based confocal laser endomicroscopy: A new method for quantitative analysis of pit structure in healthy and Crohn's disease patients

Probe-based confocal laser endomicroscopy enables microscopic examination of the digestive mucosa. (1) To identify and validate quantitative endomicroscopic criteria for evaluation of the colonic mucosa and (2) to compare these criteria between healthy and Crohn's disease patients in clinical remission. Six healthy controls and ten Crohn's disease patients in clinical remission were included in this prospective study. Methylene blue-stained biopsies of the right colon and corresponding endomicroscopic images were analyzed. Major axis, minor axis, and major axis/minor axis ratio of crypt lumens were quantified. Quantitative assessment was performed on 21 ± 4 crypt lumens per patient. Major axis/minor axis ratio values measured with endomicroscopy or methylene blue-stained biopsies were linearly correlated (r=0.63, p=0.01). All macroscopically inflamed mucosa had values of major axis/minor axis ratio higher than the median of controls. Interestingly, 50% (3/6) of Crohn's disease patients with macroscopically normal mucosa had also a higher ratio than pooled controls. Histological analysis showed that 6/7 patients with major axis/minor axis ratio superior to 1.7 had microscopic inflammation. Probe-based confocal laser endomicroscopy allows quantitative analysis of colonic pit structure. Endomicroscopic analysis of major axis/minor axis ratio allows the detection of microscopic residual inflammation with greater accuracy than standard endoscopy in Crohn's disease patients in clinical remission.

A prospective single‐centre evaluation of the intra‐individual variability of faecal calprotectin in quiescent Crohn's disease

As a non-invasive marker of gastrointestinal inflammation, faecal calprotectin (FC) is being increasingly used to guide the management of Crohn's disease. It is therefore a concern that studies have shown variability in day to day levels. To determine the degree of this intrapersonal variability in the context of quiescent Crohn's disease. A single-centre prospective study was undertaken in 143 Crohn's disease patients in clinical remission. Three faecal calprotectin levels were analysed from stool samples on consecutive days. Consistency of faecal calprotectin levels was determined by measuring the intraclass correlation (ICC). Due to higher variability at higher faecal calprotectin levels, the ICC was calculated for the log-transformed values. The reliability of detecting a 'case' of active inflammation as defined for specific concentrations of faecal calprotectin was measured by the kappa statistic. Ninety-eight complete sets of results were obtained. The ICC was 0.84 (95% CI: 0.79-0.89), which represents low variability across samples. The kappa statistic for the reliability of detecting a case as defined by an FC level of >50 μg/g was substantial at 0.648 (0.511-0.769). Day to day variability of faecal calprotectin is low in our cohort of quiescent Crohn's disease patients and the reliability of defining a 'case' is moderately good. These data provide reassurance to clinicians using a single calprotectin sample to inform therapeutic strategies in this cohort.

970 Multicenter Capsule Endoscopy Study of Small Bowel Crohn's Disease Patients in Clinical Remission: Long-Term Follow-up and Correlation With Faecal Biomarkers and Clinical Outcome

970 Multicenter Capsule Endoscopy Study of Small Bowel Crohn's Disease Patients in Clinical Remission: Long-Term Follow-up and Correlation With Faecal Biomarkers and Clinical Outcome

847r Capsule Endoscopy Findings in Small Bowel Crohn's Disease Patients in Clinical Remission: Correlation With the Crohn's Disease Activity Index, Faecal Calprotectin and S100A12

847r Capsule Endoscopy Findings in Small Bowel Crohn's Disease Patients in Clinical Remission: Correlation With the Crohn's Disease Activity Index, Faecal Calprotectin and S100A12