Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0440
M Katsaros, A Katsoula, M Kalogirou, P Paschos, P Papagiannakis, T Tsionis, O Giouleme
Background The assessment of treatment response in patients with Inflammatory Bowel Disease (IBD) is often based on clinical indices [Harvey Bradshaw index (HBI), Partial Mayo score (PMS)] and biomarkers [C - reactive protein (CRP)]. Intestinal ultrasound (IUS) has been proposed as a modality capable of objectively evaluating therapeutic response. We investigated the utility of the IUS as a tool to assess treatment response, as well as its association with HBI, PMS and CRP. Methods We included patients with an established diagnosis of IBD who initiated biologic agent (infliximab, adalimumab, ustekinumab, vedolizumab) or tofacitinib. Active disease on IUS was defined as an increase in bowel wall thickness (BWT) >3 mm in the most affected bowel segment, while the presence of a Doppler signal (CDS) in the bowel wall was also assessed. Treatment response on IUS was defined according to the International Bowel Ultrasound Group (IBUS) criteria: reduction in bowel wall thickness (in continuous measurements) >25% or >2.0 mm or >1.0 mm with concomitant reduction in CDS by 1 unit at week 14 ± 2 from the initiation of treatment. Results A total of 19 patients (11 men, 11 with Crohn's disease) underwent IUS at week 0 and week 14 ± 2, while CRP, HBI and PMS were calculated at the same time points. We included bio-naïve as well bio experienced patients (table 1). At week 0, 84.2% of patients exhibited clinical activity (HBI ≥5, PMS ≥2), median CRP was 24.7 mg /L (IQR 18.6-42.8) and median BWT was 7.1mm (IQR 6.5-7.6). At week 14 ± 2, 42.1% of patients remained clinically active, median CRP was 6.8 mg/L (IQR 4.6-20.7) and median BWT was 5.2 mm (IQR 4.6- 6.4). Overall 10/19 patients fulfilled the criteria of treatment response on IUS at week 14 ± 2. Clinical remission was observed in 8/10 patients who demonstrated therapeutic response on IUS and 3/9 patients who did not (p=0.07). Normalization of CRP value (<6mg/L) was observed in 8/10 patients who exhibited treatment response on IUS and in none of the patients who did not (p<0.001). Among the IUS parameters at baseline, a statistically significant difference was found only in the presence of fat wrapping between treatment responders and treatment non-responders (table 2). Finally, median CRP was 4.9 mg/L (IQR 2.6-6.2) in IUS treatment responders and 20.7 mg/L (IQR 10.5-28.5) in IUS treatment non-responders. (p<0.001), with median BWT being 4.7mm (IQR 3.3-5.1) and 6.4mm (IQR 6.1-6.9) respectively (p<0.001). Conclusion IUS represents an objective tool for evaluating treatment response in patients with IBD, which demonstrates a significant correlation with CRP but not with clinical indices of activity.
{"title":"P310 Intestinal ultrasound as a tool to assess treatment response in patients with Inflammatory Bowel Diseases","authors":"M Katsaros, A Katsoula, M Kalogirou, P Paschos, P Papagiannakis, T Tsionis, O Giouleme","doi":"10.1093/ecco-jcc/jjad212.0440","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0440","url":null,"abstract":"Background The assessment of treatment response in patients with Inflammatory Bowel Disease (IBD) is often based on clinical indices [Harvey Bradshaw index (HBI), Partial Mayo score (PMS)] and biomarkers [C - reactive protein (CRP)]. Intestinal ultrasound (IUS) has been proposed as a modality capable of objectively evaluating therapeutic response. We investigated the utility of the IUS as a tool to assess treatment response, as well as its association with HBI, PMS and CRP. Methods We included patients with an established diagnosis of IBD who initiated biologic agent (infliximab, adalimumab, ustekinumab, vedolizumab) or tofacitinib. Active disease on IUS was defined as an increase in bowel wall thickness (BWT) &gt;3 mm in the most affected bowel segment, while the presence of a Doppler signal (CDS) in the bowel wall was also assessed. Treatment response on IUS was defined according to the International Bowel Ultrasound Group (IBUS) criteria: reduction in bowel wall thickness (in continuous measurements) &gt;25% or &gt;2.0 mm or &gt;1.0 mm with concomitant reduction in CDS by 1 unit at week 14 ± 2 from the initiation of treatment. Results A total of 19 patients (11 men, 11 with Crohn's disease) underwent IUS at week 0 and week 14 ± 2, while CRP, HBI and PMS were calculated at the same time points. We included bio-naïve as well bio experienced patients (table 1). At week 0, 84.2% of patients exhibited clinical activity (HBI ≥5, PMS ≥2), median CRP was 24.7 mg /L (IQR 18.6-42.8) and median BWT was 7.1mm (IQR 6.5-7.6). At week 14 ± 2, 42.1% of patients remained clinically active, median CRP was 6.8 mg/L (IQR 4.6-20.7) and median BWT was 5.2 mm (IQR 4.6- 6.4). Overall 10/19 patients fulfilled the criteria of treatment response on IUS at week 14 ± 2. Clinical remission was observed in 8/10 patients who demonstrated therapeutic response on IUS and 3/9 patients who did not (p=0.07). Normalization of CRP value (&lt;6mg/L) was observed in 8/10 patients who exhibited treatment response on IUS and in none of the patients who did not (p&lt;0.001). Among the IUS parameters at baseline, a statistically significant difference was found only in the presence of fat wrapping between treatment responders and treatment non-responders (table 2). Finally, median CRP was 4.9 mg/L (IQR 2.6-6.2) in IUS treatment responders and 20.7 mg/L (IQR 10.5-28.5) in IUS treatment non-responders. (p&lt;0.001), with median BWT being 4.7mm (IQR 3.3-5.1) and 6.4mm (IQR 6.1-6.9) respectively (p&lt;0.001). Conclusion IUS represents an objective tool for evaluating treatment response in patients with IBD, which demonstrates a significant correlation with CRP but not with clinical indices of activity.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.1199
J H Bae, J B Park, J E Baek, Y J Lee, K O Kim, E S Kim, H H Jo, S W Hong, S H Park, D H Yang, B D Ye, J S Byeon, S J Myung, S K Yang, E Y Kim, S W Hwang
Background An elective switching to the subcutaneous (SC) formulation of infliximab (IFX) has shown effectiveness and safety in patients with inflammatory bowel disease (IBD) on intravenous (IV) IFX maintenance therapy. However, data on long-term outcomes in patients not in clinical remission during maintenance therapy is limited. This study aims to evaluate the long-term outcomes of SC switching in patients who were in clinical remission and not in remission during IV IFX maintenance therapy. Methods This retrospective multicentre study was conducted from January 2021 to October 2023. Clinical remission was defined as Crohn’s Disease Activity Index (CDAI) <150 for Crohn’s disease (CD) and partial Mayo score <2 for ulcerative colitis. Biological remission was defined as faecal calprotectin (FC) <250 µg/g and C-reactive protein (CRP) <0.5 mg/dL. The primary outcome measure was 1-year treatment persistence of SC IFX. Results Among 127 patients included in the study, 80 (62.9%) had CD, and 47 (37.1%) had UC. At the time of switching, 90 patients (70.9 %) were in clinical remission; whereas, 37 (29.1 %) were in a non-remission state. The treatment persistence rate at 1 year was high at 92.9%. Treatment persistence rates between the clinical remission and non-remission groups did not differ significantly (94.4% vs. 89.2%, p=0.287). In both groups, IFX pharmacokinetics and biomarkers between baseline and 12 months (p<0.01) significantly improved. The median infliximab levels increased from a baseline of 3.3 µg/mL (interquartile range [IQR] 1.3–5.1) to 14.4 µg/mL (IQR 9.4–23.0, p<0.001) at 12 months. Disease activity index was stable in the remission group, and decreased in the non-remission group (partial Mayo score, p<0.001; CDAI, p=0.063). At the one-year follow-up, clinical remission and biological remission were achieved in 86.6% and 60.6%, respectively, an increase from baseline (70.9% and 48.0%, respectively). Biologics exposure before IFX was the only significant variable associated with treatment persistence (odds ratio 5.138, 95% confidence interval 1.150–22.951, p=0.032). The concomitant use of immunomodulators was not associated. The incidence of IFX-related adverse events was 14.2%, with only three patients discontinuing treatment. Conclusion Switching to SC IFX from IV IFX maintenance therapy demonstrated high treatment persistence and favourable safety profiles, irrespective of remission status at the time of switching. Patients in both remission or non-remission states showed significant improvement in pharmacokinetics and biomarkers, and/or stable disease activity indices.
{"title":"P1069 One-year clinical outcomes of switching to subcutaneous infliximab in patients with inflammatory bowel disease on maintenance of intravenous infliximab therapy with or without remission: A multicentre cohort study","authors":"J H Bae, J B Park, J E Baek, Y J Lee, K O Kim, E S Kim, H H Jo, S W Hong, S H Park, D H Yang, B D Ye, J S Byeon, S J Myung, S K Yang, E Y Kim, S W Hwang","doi":"10.1093/ecco-jcc/jjad212.1199","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1199","url":null,"abstract":"Background An elective switching to the subcutaneous (SC) formulation of infliximab (IFX) has shown effectiveness and safety in patients with inflammatory bowel disease (IBD) on intravenous (IV) IFX maintenance therapy. However, data on long-term outcomes in patients not in clinical remission during maintenance therapy is limited. This study aims to evaluate the long-term outcomes of SC switching in patients who were in clinical remission and not in remission during IV IFX maintenance therapy. Methods This retrospective multicentre study was conducted from January 2021 to October 2023. Clinical remission was defined as Crohn’s Disease Activity Index (CDAI) &lt;150 for Crohn’s disease (CD) and partial Mayo score &lt;2 for ulcerative colitis. Biological remission was defined as faecal calprotectin (FC) &lt;250 µg/g and C-reactive protein (CRP) &lt;0.5 mg/dL. The primary outcome measure was 1-year treatment persistence of SC IFX. Results Among 127 patients included in the study, 80 (62.9%) had CD, and 47 (37.1%) had UC. At the time of switching, 90 patients (70.9 %) were in clinical remission; whereas, 37 (29.1 %) were in a non-remission state. The treatment persistence rate at 1 year was high at 92.9%. Treatment persistence rates between the clinical remission and non-remission groups did not differ significantly (94.4% vs. 89.2%, p=0.287). In both groups, IFX pharmacokinetics and biomarkers between baseline and 12 months (p&lt;0.01) significantly improved. The median infliximab levels increased from a baseline of 3.3 µg/mL (interquartile range [IQR] 1.3–5.1) to 14.4 µg/mL (IQR 9.4–23.0, p&lt;0.001) at 12 months. Disease activity index was stable in the remission group, and decreased in the non-remission group (partial Mayo score, p&lt;0.001; CDAI, p=0.063). At the one-year follow-up, clinical remission and biological remission were achieved in 86.6% and 60.6%, respectively, an increase from baseline (70.9% and 48.0%, respectively). Biologics exposure before IFX was the only significant variable associated with treatment persistence (odds ratio 5.138, 95% confidence interval 1.150–22.951, p=0.032). The concomitant use of immunomodulators was not associated. The incidence of IFX-related adverse events was 14.2%, with only three patients discontinuing treatment. Conclusion Switching to SC IFX from IV IFX maintenance therapy demonstrated high treatment persistence and favourable safety profiles, irrespective of remission status at the time of switching. Patients in both remission or non-remission states showed significant improvement in pharmacokinetics and biomarkers, and/or stable disease activity indices.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0826
S Rohekar, T Boyd, R Lambert, M Beaton, N Chande, J Gregor, H Lennox, K McIntosh, T Ponich, A Rahman, T Sharma, M Sey, M Tauqir, V Jairath
Background Prior case series indicated a temporal relationship between use of vedolizumab and new-onset spondyloarthritis. Methods We aimed to evaluate the relationship between initiation of vedolizumab and development of new-onset spondyloarthritis in patients with inflammatory bowel disease, through serial clinical evaluation and magnetic resonance imaging. A single-centre prospective observational study of 24 patients with inflammatory bowel disease. Patients were eligible if they had active ulcerative colitis or Crohn’s disease and initiating vedolizumab, had no prior history of arthritis or spondyloarthritis and suitable for undergoing serial magnetic resonance imaging. Clinical evaluation was performed by a rheumatologist prior to first dose of vedolizumab and at weeks 8 and 24 weeks after administration. Axial magnetic resonance imaging was performed at baseline, weeks 8 and 24 and evaluated by a blinded central reader. Results Nine tumour necrosis factor inhibitor-naïve patients (4 male; mean age 53.2 yrs; 6 ulcerative colitis; 3 Crohn’s disease) and eight tumour necrosis factor inhibitor-experienced patients (7 male; mean age 48 yrs; 3 ulcerative colitis; 5 Crohn’s disease) completed all assessments. No patients developed new features of axial arthritis either on clinical or blinded radiological assessment at weeks 8 or 24, nor any features of peripheral spondyloarthritis including inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp). Both the tumour necrosis factor inhibitor-naive and tumour necrosis factor inhibitor-experienced patients demonstrated good intestinal response to vedolizumab. Conclusion Initiation of vedolizumab did not induce new features of axial or peripheral spondyloarthritis in tumour necrosis factor inhibitor-experienced or tumour necrosis factor inhibitor-naive patients with inflammatory bowel disease.
{"title":"P696 Initiation of Vedolizumab did not provoke new-onset spondylarthritis in patients with inflammatory bowel disease: A Prospective Study Including Rheumatological and Blinded Imaging Assessments","authors":"S Rohekar, T Boyd, R Lambert, M Beaton, N Chande, J Gregor, H Lennox, K McIntosh, T Ponich, A Rahman, T Sharma, M Sey, M Tauqir, V Jairath","doi":"10.1093/ecco-jcc/jjad212.0826","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0826","url":null,"abstract":"Background Prior case series indicated a temporal relationship between use of vedolizumab and new-onset spondyloarthritis. Methods We aimed to evaluate the relationship between initiation of vedolizumab and development of new-onset spondyloarthritis in patients with inflammatory bowel disease, through serial clinical evaluation and magnetic resonance imaging. A single-centre prospective observational study of 24 patients with inflammatory bowel disease. Patients were eligible if they had active ulcerative colitis or Crohn’s disease and initiating vedolizumab, had no prior history of arthritis or spondyloarthritis and suitable for undergoing serial magnetic resonance imaging. Clinical evaluation was performed by a rheumatologist prior to first dose of vedolizumab and at weeks 8 and 24 weeks after administration. Axial magnetic resonance imaging was performed at baseline, weeks 8 and 24 and evaluated by a blinded central reader. Results Nine tumour necrosis factor inhibitor-naïve patients (4 male; mean age 53.2 yrs; 6 ulcerative colitis; 3 Crohn’s disease) and eight tumour necrosis factor inhibitor-experienced patients (7 male; mean age 48 yrs; 3 ulcerative colitis; 5 Crohn’s disease) completed all assessments. No patients developed new features of axial arthritis either on clinical or blinded radiological assessment at weeks 8 or 24, nor any features of peripheral spondyloarthritis including inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp). Both the tumour necrosis factor inhibitor-naive and tumour necrosis factor inhibitor-experienced patients demonstrated good intestinal response to vedolizumab. Conclusion Initiation of vedolizumab did not induce new features of axial or peripheral spondyloarthritis in tumour necrosis factor inhibitor-experienced or tumour necrosis factor inhibitor-naive patients with inflammatory bowel disease.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0103
M Malham, S Jansson, H A S Ingels, M H Jørgensen, N Roed, A V Wewer, M P Fox
Background Patients with pediatric-onset immune-mediated inflammatory diseases (pIMID) show more aggressive phenotypes compared to patients diagnosed as adults. Despite this, data on mortality is extrapolated from patients diagnosed in adulthood, which might underestimate the actual risk. We aim to estimate the effect of pIMID compared to reference individuals from the general population on the long-term risk of all-cause mortality. Methods A population-based cohort study using the nationwide Danish health care registers. We included all patients diagnosed with pIMID in Denmark from 1980 to 2018 and matched them to up to ten reference individuals from the general population (with no recorded IMID) based on sex, age at diagnosis, and area of residence. Exposure was pIMID, defined as ICD codes indicative of autoimmune hepatitis, primary sclerosing cholangitis, Crohn’s disease, ulcerative colitis, juvenile idiopathic arthritis, system lupus erythematosus, or vasculitis registered before age 18. The primary outcome was all-cause mortality. The secondary outcome was cause-specific mortality. Cox survival analysis was used to estimate hazard ratios (HR) and Aalen survival analysis to estimate rate differences with corresponding 95% confidence intervals (CI) adjusted for the year of diagnosis and family income. Denmark has universal free health care, and health care data can be accessed through the nationwide health registers, continuously updated since 1980. Results We included 11,581 individuals diagnosed with pIMID, and 99,665 matched reference individuals, accounting for 1,371,994 person-years of follow-up. Median age at pIMID diagnosis was 12.6 years (IQR: 7.9 – 15.9). During follow-up, 152 pIMID patients and 316 reference individuals died, resulting in an all-cause mortality adjusted HR (aHR) of 3.8 (95% confidence interval [CI]: 3.1-4.7) compared to reference individuals without pIMID. This corresponded to 7.8 (95%CI: 6.1-9.5) additional deaths per 10,000 person-years. The strongest associations were found for gastrointestinal disorders (aHR 22.8 [95%CI: 9.6-64.1]), gastrointestinal cancers (aHR 19.2 [95%CI: 5.0-74.2]), and lymphoproliferative diseases (aHR 6.8 [95%CI: 2.8-16.8]). The aHR of suicide was 2.9 (95%CI: 1.6-5.0). Conclusion Patients diagnosed with pIMID have a four-fold increased risk of mortality when followed into adulthood. This underlines the severe disease course of pIMID and highlights the need for lifelong multidisciplinary care.
{"title":"DOP63 Mortality in Pediatric-onset Immune-Mediated Inflammatory Disease – A Nationwide Study","authors":"M Malham, S Jansson, H A S Ingels, M H Jørgensen, N Roed, A V Wewer, M P Fox","doi":"10.1093/ecco-jcc/jjad212.0103","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0103","url":null,"abstract":"Background Patients with pediatric-onset immune-mediated inflammatory diseases (pIMID) show more aggressive phenotypes compared to patients diagnosed as adults. Despite this, data on mortality is extrapolated from patients diagnosed in adulthood, which might underestimate the actual risk. We aim to estimate the effect of pIMID compared to reference individuals from the general population on the long-term risk of all-cause mortality. Methods A population-based cohort study using the nationwide Danish health care registers. We included all patients diagnosed with pIMID in Denmark from 1980 to 2018 and matched them to up to ten reference individuals from the general population (with no recorded IMID) based on sex, age at diagnosis, and area of residence. Exposure was pIMID, defined as ICD codes indicative of autoimmune hepatitis, primary sclerosing cholangitis, Crohn’s disease, ulcerative colitis, juvenile idiopathic arthritis, system lupus erythematosus, or vasculitis registered before age 18. The primary outcome was all-cause mortality. The secondary outcome was cause-specific mortality. Cox survival analysis was used to estimate hazard ratios (HR) and Aalen survival analysis to estimate rate differences with corresponding 95% confidence intervals (CI) adjusted for the year of diagnosis and family income. Denmark has universal free health care, and health care data can be accessed through the nationwide health registers, continuously updated since 1980. Results We included 11,581 individuals diagnosed with pIMID, and 99,665 matched reference individuals, accounting for 1,371,994 person-years of follow-up. Median age at pIMID diagnosis was 12.6 years (IQR: 7.9 – 15.9). During follow-up, 152 pIMID patients and 316 reference individuals died, resulting in an all-cause mortality adjusted HR (aHR) of 3.8 (95% confidence interval [CI]: 3.1-4.7) compared to reference individuals without pIMID. This corresponded to 7.8 (95%CI: 6.1-9.5) additional deaths per 10,000 person-years. The strongest associations were found for gastrointestinal disorders (aHR 22.8 [95%CI: 9.6-64.1]), gastrointestinal cancers (aHR 19.2 [95%CI: 5.0-74.2]), and lymphoproliferative diseases (aHR 6.8 [95%CI: 2.8-16.8]). The aHR of suicide was 2.9 (95%CI: 1.6-5.0). Conclusion Patients diagnosed with pIMID have a four-fold increased risk of mortality when followed into adulthood. This underlines the severe disease course of pIMID and highlights the need for lifelong multidisciplinary care.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.1016
X Serra-Ruiz, E Céspedes Martínez, L Mayorga Ayala, C Herrera de-Guise, V Robles Alonso, Z Pérez Martínez, E Oller, N Borruel Sainz
Background It is unclear whether ustekinumab (UST) concentrations can predict the clinical course of inflammatory bowel disease (IBD) and guide treatment algorithms during the induction phase. The aim of our study was to assess the association between serum UST concentrations during the induction phase and clinical outcomes at week 24 and to determine the validity of a UST threshold for guiding intensification strategies. Methods We conducted a retrospective study including Crohn's disease (CD) and ulcerative colitis (UC) patients who started UST treatment between June 2022 and February 2023. Intensification strategies were determined according to standard clinical practice. UST concentrations were collected at weeks 8, 16, and 24. Quartile analysis and logistic regression were performed to evaluate the association between UST concentrations and treatment targets. Definitions are clinical steroid-free remission as a Harvey-Bradshaw index <5 and a partial Mayo score <2; endoscopic remission as a simple endoscopic score (SES-CD) ≤2 and Mayo endoscopic score (EMS) ≤1; and endoscopic response as a ≥50% reduction in SES-CD and ≥1 point in EMS. Results We included 42 patients (CD: 24). At week 24, clinical remission rates of 67% and endoscopic response and remission rates of 57% and 28%, respectively, were achieved. At week 24, the majority of patients continued intensified treatment: 90 mg subcutaneously every 4 weeks in 55% and 130 mg intravenously every 4 weeks in 36%. Patients who achieved an endoscopic response at week 24 had higher UST levels at week 8 (4.1 vs. 2.9 µg/ml, p=0.029). No significant differences between endoscopic remission rates and UST levels at any week were observed. The differences observed in the quartile analysis between the UST concentrations at week 8 and the endoscopic response were not statistically significant (p=0.451). The area under the ROC curve value for UST levels at week 8 to predict endoscopic response was 0.734 (p=0.012). Logistic regression analysis identified prior exposure to vedolizumab and absence of perianal disease as predictors of endoscopic response and remission at week 24 in univariate analysis, but not in multivariate analysis. No association was observed between UST levels and drug persistence rates. Conclusion In this real-world cohort, higher UST concentrations at week 8 were associated with higher rates of endoscopic response at week 24. A reliable concentration threshold for predicting endoscopic response and treatment intensification could not be determined, probably due to the insufficient number of patients included in the study and the relatively poor performance of the ROC curve. Prospective, randomized studies are needed to validate these results.
{"title":"P886 Ustekinumab concentrations in induction are associated with mid-term endoscopic outcomes in patients with inflammatory bowel disease","authors":"X Serra-Ruiz, E Céspedes Martínez, L Mayorga Ayala, C Herrera de-Guise, V Robles Alonso, Z Pérez Martínez, E Oller, N Borruel Sainz","doi":"10.1093/ecco-jcc/jjad212.1016","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1016","url":null,"abstract":"Background It is unclear whether ustekinumab (UST) concentrations can predict the clinical course of inflammatory bowel disease (IBD) and guide treatment algorithms during the induction phase. The aim of our study was to assess the association between serum UST concentrations during the induction phase and clinical outcomes at week 24 and to determine the validity of a UST threshold for guiding intensification strategies. Methods We conducted a retrospective study including Crohn's disease (CD) and ulcerative colitis (UC) patients who started UST treatment between June 2022 and February 2023. Intensification strategies were determined according to standard clinical practice. UST concentrations were collected at weeks 8, 16, and 24. Quartile analysis and logistic regression were performed to evaluate the association between UST concentrations and treatment targets. Definitions are clinical steroid-free remission as a Harvey-Bradshaw index &lt;5 and a partial Mayo score &lt;2; endoscopic remission as a simple endoscopic score (SES-CD) ≤2 and Mayo endoscopic score (EMS) ≤1; and endoscopic response as a ≥50% reduction in SES-CD and ≥1 point in EMS. Results We included 42 patients (CD: 24). At week 24, clinical remission rates of 67% and endoscopic response and remission rates of 57% and 28%, respectively, were achieved. At week 24, the majority of patients continued intensified treatment: 90 mg subcutaneously every 4 weeks in 55% and 130 mg intravenously every 4 weeks in 36%. Patients who achieved an endoscopic response at week 24 had higher UST levels at week 8 (4.1 vs. 2.9 µg/ml, p=0.029). No significant differences between endoscopic remission rates and UST levels at any week were observed. The differences observed in the quartile analysis between the UST concentrations at week 8 and the endoscopic response were not statistically significant (p=0.451). The area under the ROC curve value for UST levels at week 8 to predict endoscopic response was 0.734 (p=0.012). Logistic regression analysis identified prior exposure to vedolizumab and absence of perianal disease as predictors of endoscopic response and remission at week 24 in univariate analysis, but not in multivariate analysis. No association was observed between UST levels and drug persistence rates. Conclusion In this real-world cohort, higher UST concentrations at week 8 were associated with higher rates of endoscopic response at week 24. A reliable concentration threshold for predicting endoscopic response and treatment intensification could not be determined, probably due to the insufficient number of patients included in the study and the relatively poor performance of the ROC curve. Prospective, randomized studies are needed to validate these results.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.1375
P Avery, K Kemp, L Dibley, S Green
Background Since the COVID-19 pandemic, the use of health tools (video/phone consultations, patient portals, and digital applications) has increased in the clinical management of patients with Inflammatory Bowel Disease (PIBD). We aimed to evidence the acceptability of eHealth tools by investigating the shared experience of PIBD and healthcare professionals (HCPs) in using eHealth to carry out follow-up appointments and support self-management. Methods An exploratory qualitative method was used. Participants were recruited via professional networks, social media platforms, Crohn's and Colitis UK website and newsletters. Semi-structured interviews were conducted remotely in April/May 2023 using MS Teams or Zoom. Transcripts were analysed using a thematic analysis. Results Fifteen HCPs (13 female) participated: IBD specialist nurses (n=9); gastroenterologists (n=2), pharmacists (n=2) and Dieticians (n=2). The 16 PIBD (10 female) participants were living with Crohn’s Disease (n=9), Ulcerative Colitis (n=6), and Inflammatory Bowel Disease Unclassified (n=1); age was reported in ranges 18 -24 (n=3), 24-34 (n=1), 35-54 (n=8), and 55-65 (n=2) and 75-85 (n=1). Time since IBD diagnosis ranged from < 6 months - 43 years (mean time 18.7 years). Some participants had pre-diagnosis symptoms for at least one year (81%) to over five years (25%). Four themes emerged: • Flexibility and Accessibility: PIBD appreciated the ease of virtual appointments and access to test results and information but wanted flexibility and a personal approach to their care; eHealth connected them to their IBD team more easily. • Resource: HCPs wanted better digital training since remote assessment skills differ from in-person assessment skills. They also identified the need for admin support when planning to implement eHealth tools. HCPs and PIBD wondered whether eHealth was primarily a cost-savings exercise, whilst the need for resource efficiencies across the health service was recognised. • e-Literacy: HCPs were concerned that some older PIBD might be excluded from accessing eHealth due to e-literacy and capability issues, perceiving that eHealth is for the younger generation. • The Human Factor: PIBD and HCPs wanted to have already met in person anyone they engaged with later virtually. For PIBD, in-person consultations meant they felt seen or understood, and they described the importance of hands-on abdominal examinations in reassuring them about their health status. Conclusion There is an acceptability of eHealth to support the care of PIBD, but HCPs and PIBD still value the Human factor. Concerns over Resourcing, Flexibility and Accessibility and e-Literacy may need addressing to avoid these becoming barriers to the benefits of virtual healthcare in supporting PIBD.
{"title":"N03 Flexibility & Accessibility, e-Literacy, Resourcing and The Human Factor: Early Lessons from EIBD, a UK Qualitative Interview Study","authors":"P Avery, K Kemp, L Dibley, S Green","doi":"10.1093/ecco-jcc/jjad212.1375","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1375","url":null,"abstract":"Background Since the COVID-19 pandemic, the use of health tools (video/phone consultations, patient portals, and digital applications) has increased in the clinical management of patients with Inflammatory Bowel Disease (PIBD). We aimed to evidence the acceptability of eHealth tools by investigating the shared experience of PIBD and healthcare professionals (HCPs) in using eHealth to carry out follow-up appointments and support self-management. Methods An exploratory qualitative method was used. Participants were recruited via professional networks, social media platforms, Crohn's and Colitis UK website and newsletters. Semi-structured interviews were conducted remotely in April/May 2023 using MS Teams or Zoom. Transcripts were analysed using a thematic analysis. Results Fifteen HCPs (13 female) participated: IBD specialist nurses (n=9); gastroenterologists (n=2), pharmacists (n=2) and Dieticians (n=2). The 16 PIBD (10 female) participants were living with Crohn’s Disease (n=9), Ulcerative Colitis (n=6), and Inflammatory Bowel Disease Unclassified (n=1); age was reported in ranges 18 -24 (n=3), 24-34 (n=1), 35-54 (n=8), and 55-65 (n=2) and 75-85 (n=1). Time since IBD diagnosis ranged from &lt; 6 months - 43 years (mean time 18.7 years). Some participants had pre-diagnosis symptoms for at least one year (81%) to over five years (25%). Four themes emerged: • Flexibility and Accessibility: PIBD appreciated the ease of virtual appointments and access to test results and information but wanted flexibility and a personal approach to their care; eHealth connected them to their IBD team more easily. • Resource: HCPs wanted better digital training since remote assessment skills differ from in-person assessment skills. They also identified the need for admin support when planning to implement eHealth tools. HCPs and PIBD wondered whether eHealth was primarily a cost-savings exercise, whilst the need for resource efficiencies across the health service was recognised. • e-Literacy: HCPs were concerned that some older PIBD might be excluded from accessing eHealth due to e-literacy and capability issues, perceiving that eHealth is for the younger generation. • The Human Factor: PIBD and HCPs wanted to have already met in person anyone they engaged with later virtually. For PIBD, in-person consultations meant they felt seen or understood, and they described the importance of hands-on abdominal examinations in reassuring them about their health status. Conclusion There is an acceptability of eHealth to support the care of PIBD, but HCPs and PIBD still value the Human factor. Concerns over Resourcing, Flexibility and Accessibility and e-Literacy may need addressing to avoid these becoming barriers to the benefits of virtual healthcare in supporting PIBD.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0348
A Singh, C Kakkar, A Bhardwaj, P A Bonaffini, M Goyal, M Marwah, A Sachdeva, N Bansal, R Mahajan, V Midha, A Sood
Background Magnetic resonance imaging (MRI) is the standard for evaluating perianal fistulae. Perianal fistula can be the first manifestation of CD, and needs to be differentiated from non-CD associated perianal fistula. This study sought to identify the variations in MRI characteristics of perianal fistulas in patients with and without inflammatory bowel disease (IBD), considering the potential implications for treatment decisions. Methods This was a single-center cross-sectional analysis of patients who underwent pelvic MRI for assessment of perianal fistula between January 2021 and June 2022 at Dayanand Medical College and Hospital (DMCH), Ludhiana, India. Patients who underwent dedicated MRI fistula protocol were included. Patients with prior anal resection or anastomosis, anorectal tumor, or equivocal imaging findings that could not be definitely assessed as a fistula were excluded. The following features were assessed: anatomic type of fistula (Parks classification), luminal origin (hour clock position), anal verge distance, signs of acute inflammation, circumference of anus involved by inflammation, presence of rectal inflammation, and abscess. Results Between January 2022 and December 2022, a total of 287 MRI scans were conducted to assess for perianal fistulae. Out of these, 119 MRI scans met the eligibility criteria and 32(26.89%) were associated with an established clinical diagnosis of CD. A higher proportion of females had CD-associated perianal fistula compared to non-CD perianal fistula. A significantly greater percentage of CD-associated perianal fistulas exhibited supra-levator extension, multiple and branched fistula tracts, and ≥2 internal and external openings. Patients with CD had higher prevalence of concurrent perianal abscess, proctitis, anorectal strictures, and a greater number of clock hours of inflamed anal circumference, compared to patients with cryptoglandular fistula. (Table 1) On multivariate logistic regression analysis, female sex, ≥2 internal openings, proctitis and height of the mucosal origin of the fistula from the anal verge >1.85 cm independently predicted the perianal fistula to be associated with CD. We constructed the DMCH index as follows: DMCH index: (3xfemale sex) + (3x≥2 internal openings of the fistula tract) + (6xrectal wall thickening) + (2xheight of mucosal origin of the fistula from anal verge >1.85 cm) The DMCH index greater than 7 identified the perianal fistulae associated with CD with a sensitivity of 84% and specificity of 91% [Area under curve 0.91; 95% CI 0.85-0.97; P< 0.0001].(Figure 1) Conclusion The DMCH index identifies CD associates perianal fistula with a high level of accuracy. These findings require validation and confirmation in independent, multi-reader studies.
{"title":"P218 Development of Magnetic Resonance Imaging based index to differentiate Crohn’s disease associated perianal fistula and cryptoglandular perianal fistula","authors":"A Singh, C Kakkar, A Bhardwaj, P A Bonaffini, M Goyal, M Marwah, A Sachdeva, N Bansal, R Mahajan, V Midha, A Sood","doi":"10.1093/ecco-jcc/jjad212.0348","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0348","url":null,"abstract":"Background Magnetic resonance imaging (MRI) is the standard for evaluating perianal fistulae. Perianal fistula can be the first manifestation of CD, and needs to be differentiated from non-CD associated perianal fistula. This study sought to identify the variations in MRI characteristics of perianal fistulas in patients with and without inflammatory bowel disease (IBD), considering the potential implications for treatment decisions. Methods This was a single-center cross-sectional analysis of patients who underwent pelvic MRI for assessment of perianal fistula between January 2021 and June 2022 at Dayanand Medical College and Hospital (DMCH), Ludhiana, India. Patients who underwent dedicated MRI fistula protocol were included. Patients with prior anal resection or anastomosis, anorectal tumor, or equivocal imaging findings that could not be definitely assessed as a fistula were excluded. The following features were assessed: anatomic type of fistula (Parks classification), luminal origin (hour clock position), anal verge distance, signs of acute inflammation, circumference of anus involved by inflammation, presence of rectal inflammation, and abscess. Results Between January 2022 and December 2022, a total of 287 MRI scans were conducted to assess for perianal fistulae. Out of these, 119 MRI scans met the eligibility criteria and 32(26.89%) were associated with an established clinical diagnosis of CD. A higher proportion of females had CD-associated perianal fistula compared to non-CD perianal fistula. A significantly greater percentage of CD-associated perianal fistulas exhibited supra-levator extension, multiple and branched fistula tracts, and ≥2 internal and external openings. Patients with CD had higher prevalence of concurrent perianal abscess, proctitis, anorectal strictures, and a greater number of clock hours of inflamed anal circumference, compared to patients with cryptoglandular fistula. (Table 1) On multivariate logistic regression analysis, female sex, ≥2 internal openings, proctitis and height of the mucosal origin of the fistula from the anal verge &gt;1.85 cm independently predicted the perianal fistula to be associated with CD. We constructed the DMCH index as follows: DMCH index: (3xfemale sex) + (3x≥2 internal openings of the fistula tract) + (6xrectal wall thickening) + (2xheight of mucosal origin of the fistula from anal verge &gt;1.85 cm) The DMCH index greater than 7 identified the perianal fistulae associated with CD with a sensitivity of 84% and specificity of 91% [Area under curve 0.91; 95% CI 0.85-0.97; P&lt; 0.0001].(Figure 1) Conclusion The DMCH index identifies CD associates perianal fistula with a high level of accuracy. These findings require validation and confirmation in independent, multi-reader studies.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.1119
B Gros, N Manceñido Marcos, J Guardiola, I Alonso Abreu, I Rodríguez Lago, R Alvarado, Á Ponferrada, J Orobitg Bernades, F Argüelles-Arias, F Mesonero, I Guerra, F Cañete, L Madero, P Borràs, G E Rodríguez, M Iborra, J Castro, A Caballero Mateos, M Barreiro-de Acosta, J M Huguet Malavés, E Brunet-Mas, F López Romero-Salazar, B Caballol, Y Zabana, C Suria Bolufer, P Soto, B Castro, S Marín, S Porto-Silva, J M Benítez, A Gutierrez, E Iglesias-Flores
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.
{"title":"P989 Switching from intravenous to subcutaneous vedolizumab in patients with inflammatory bowel disease in clinical remission: a multicenter study from GETECCU","authors":"B Gros, N Manceñido Marcos, J Guardiola, I Alonso Abreu, I Rodríguez Lago, R Alvarado, Á Ponferrada, J Orobitg Bernades, F Argüelles-Arias, F Mesonero, I Guerra, F Cañete, L Madero, P Borràs, G E Rodríguez, M Iborra, J Castro, A Caballero Mateos, M Barreiro-de Acosta, J M Huguet Malavés, E Brunet-Mas, F López Romero-Salazar, B Caballol, Y Zabana, C Suria Bolufer, P Soto, B Castro, S Marín, S Porto-Silva, J M Benítez, A Gutierrez, E Iglesias-Flores","doi":"10.1093/ecco-jcc/jjad212.1119","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1119","url":null,"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.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0873
A Croft, S Okano, G Hartel, A Lord, G Walker, G Radford-Smith
Background An episode of acute ulcerative colitis (UC) represents an important watershed moment in a patient’s disease course. Foreknowledge of a patient's likely response to intravenous corticosteroid therapy has significant clinical utility. Using a large prospectively collected acute UC patient database and machine learning-based techniques we aimed to derive and validate a personalised algorithm for identifying patients at high risk of corticosteroid therapy failure from variables available at hospital presentation. Methods A prospectively collected database of 600 consecutive presentations of acute UC was collated at a single referral centre between 1996 and 2022. An AIC-based Elastic Net model was used to select variables on the 419 earliest presentations of acute UC (1996-2017). Two risk-scoring algorithms, with and without utilising additional endoscopic variables, were constructed using logistic regression models. These risk scores were then validated on a separate cohort of 181 acute UC presentations (2018-2022). Results The partial risk of rescue (ROR) score included the admission indices of oral corticosteroid treatment; bowel frequency ≥6/24 hours; albumin; CRP ≥12mg/ml and log10CRP. The full ROR score incorporates the same variables with the addition of the Mayo endoscopic subscore and disease extent. The ROC AUCs in the validation cohort were 0.76 (95% CI: 0.69-0.83) and 0.78 (95% CI: 0.71-0.85) for the partial and full ROR scores, respectively. When incomplete cases were excluded, the full ROR score validation cohort ROC AUC increased from 0.78 to 0.80. Conclusion These pragmatic personalised risk scores (available at www.severecolitis.com) have comparably strong performance characteristics and usability enabling the identification of individuals at high risk of corticosteroid treatment failure before or after endoscopic assessment. These patients may be suitable for consideration of early treatment escalation or screening for participation in clinical trials.
{"title":"P743 A personalised algorithm predicting the risk of intravenous corticosteroid failure in acute ulcerative colitis","authors":"A Croft, S Okano, G Hartel, A Lord, G Walker, G Radford-Smith","doi":"10.1093/ecco-jcc/jjad212.0873","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0873","url":null,"abstract":"Background An episode of acute ulcerative colitis (UC) represents an important watershed moment in a patient’s disease course. Foreknowledge of a patient's likely response to intravenous corticosteroid therapy has significant clinical utility. Using a large prospectively collected acute UC patient database and machine learning-based techniques we aimed to derive and validate a personalised algorithm for identifying patients at high risk of corticosteroid therapy failure from variables available at hospital presentation. Methods A prospectively collected database of 600 consecutive presentations of acute UC was collated at a single referral centre between 1996 and 2022. An AIC-based Elastic Net model was used to select variables on the 419 earliest presentations of acute UC (1996-2017). Two risk-scoring algorithms, with and without utilising additional endoscopic variables, were constructed using logistic regression models. These risk scores were then validated on a separate cohort of 181 acute UC presentations (2018-2022). Results The partial risk of rescue (ROR) score included the admission indices of oral corticosteroid treatment; bowel frequency ≥6/24 hours; albumin; CRP ≥12mg/ml and log10CRP. The full ROR score incorporates the same variables with the addition of the Mayo endoscopic subscore and disease extent. The ROC AUCs in the validation cohort were 0.76 (95% CI: 0.69-0.83) and 0.78 (95% CI: 0.71-0.85) for the partial and full ROR scores, respectively. When incomplete cases were excluded, the full ROR score validation cohort ROC AUC increased from 0.78 to 0.80. Conclusion These pragmatic personalised risk scores (available at www.severecolitis.com) have comparably strong performance characteristics and usability enabling the identification of individuals at high risk of corticosteroid treatment failure before or after endoscopic assessment. These patients may be suitable for consideration of early treatment escalation or screening for participation in clinical trials.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.0146
I Jacobs, J Cremer, M Ferrante, J Sabino, S Vermeire, C Breynaert, T Vanuytsel, B Verstockt
Background Patients with ulcerative colitis (UC) are often treated with biological therapies or small molecules. Knowledge about the impact of these therapies on the intestinal and peripheral blood immune cell composition is scarce. Therefore, we investigated how advanced therapies modulate immune cell distribution in UC patients. Methods We included 30 UC patients (53% male, median age 42 years) who started a biological or small molecule. Before the first drug administration, mucosal colonic biopsies and a peripheral blood sample were obtained. At the end of induction, colonic biopsies and peripheral blood were sampled again. Patients starting adalimumab (n=2), infliximab (n=3), vedolizumab (n=11), ustekinumab (n=6), ozanimod (n=2) and the JAK inhibitors filgotinib (n=3) and tofacitinib (n=3) were included. Endoscopic improvement was defined as a Mayo endoscopic subscore of 0-1 at the end of induction. From the biopsies, a single-cell suspension was made. Intestinal and circulating immune cells were characterized via flow cytometry. Statistical analysis was performed using a paired t-test. Results Independent of the mechanism of action (MOA), patients responding to therapy showed a decrease of colonic granulocytes (neutrophils (p<0.0001) (Figure 1A), basophils (p<0.0001) (Figure 1B) and eosinophils (p=0.008) (Figure 1C)), active eosinophils (p=0.002) (Figure 1D)), B cells (p=0.05) (Figure 1E), regulatory T cells (p<0.0001) (Figure 1F) and T helper (Th) 2 cells (p=0.02) (Figure 1G), balanced with an increase of Th1 cells (p=0.03) (Figure 1H). In peripheral blood, eosinophils increased in patients not responding to therapy (p=0.05) (Figure 1I). Furthermore, we observed that only patients starting vedolizumab (n=11) showed a decrease in colonic eosinophils (p=0.02) (Figure 1J), active eosinophils (p=0.002) (Figure 1K), B cells (p=0.03) (Figure 1L) and T cells (p=0.004) (Figure 1M). Considering only non-vedolizumab patients (n=19), we did not observe this effect. Conclusion UC patients responding to advanced therapies showed a different intestinal immune cell distribution compared to non-responders, regardless of MOA. Vedolizumab therapy furthermore decreased several mucosal immune cell subsets that migrate to the gut through α4β7-MAdCAM-1 binding. While the effect of vedolizumab on B cells and T cells was previously described, we have now potentially identified an additional eosinophil-reducing effect in the colon.
背景溃疡性结肠炎（UC）患者通常接受生物疗法或小分子药物治疗。有关这些疗法对肠道和外周血免疫细胞组成的影响的知识很少。因此，我们研究了先进疗法如何调节 UC 患者的免疫细胞分布。方法 我们纳入了 30 名开始接受生物或小分子药物治疗的 UC 患者（53% 为男性，中位年龄 42 岁）。首次用药前，我们采集了结肠粘膜活检样本和外周血样本。在诱导治疗结束时，再次采集结肠活检和外周血样本。开始使用阿达木单抗（2例）、英夫利昔单抗（3例）、维多珠单抗（11例）、乌司他珠单抗（6例）、奥扎尼莫德（2例）以及JAK抑制剂非格替尼（3例）和托法替尼（3例）的患者均被纳入其中。内镜改善的定义是在诱导结束时梅奥内镜子评分为0-1。从活检组织中提取单细胞悬液。通过流式细胞术鉴定肠道和循环免疫细胞。统计分析采用配对 t 检验。结果 与作用机制（MOA）无关，对治疗有反应的患者结肠粒细胞（中性粒细胞（p<0.0001）（图 1A）、嗜碱性粒细胞（p<0.0001）（图 1B）和嗜酸性粒细胞（p=0.008）（图 1C））、活性嗜酸性粒细胞（p=0.002）（图 1D））、B 细胞（p=0.05）（图 1E）、调节性 T 细胞（p<0.0001）（图 1F）和 T 辅助（Th）2 细胞（p=0.02）（图 1G），与 Th1 细胞的增加（p=0.03）（图 1H）相平衡。在外周血中，对治疗无反应的患者嗜酸性粒细胞增加（p=0.05）（图 1I）。此外，我们还观察到，只有开始使用维多利珠单抗的患者（n=11）的结肠嗜酸性粒细胞（p=0.02）（图 1J）、活性嗜酸性粒细胞（p=0.002）（图 1K）、B 细胞（p=0.03）（图 1L）和 T 细胞（p=0.004）（图 1M）有所减少。仅考虑非韦多珠单抗患者（n=19），我们没有观察到这种效应。结论 对晚期疗法有反应的 UC 患者的肠道免疫细胞分布与无反应者不同，与 MOA 无关。维多珠单抗疗法进一步减少了通过α4β7-MAdCAM-1结合迁移到肠道的多个粘膜免疫细胞亚群。虽然维多珠单抗对 B 细胞和 T 细胞的作用之前已有描述，但我们现在可能又发现了一种减少结肠中嗜酸性粒细胞的作用。
{"title":"P016 Reduction of mucosal (active) eosinophils, B cells and T cells after vedolizumab therapy in patients with ulcerative colitis","authors":"I Jacobs, J Cremer, M Ferrante, J Sabino, S Vermeire, C Breynaert, T Vanuytsel, B Verstockt","doi":"10.1093/ecco-jcc/jjad212.0146","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0146","url":null,"abstract":"Background Patients with ulcerative colitis (UC) are often treated with biological therapies or small molecules. Knowledge about the impact of these therapies on the intestinal and peripheral blood immune cell composition is scarce. Therefore, we investigated how advanced therapies modulate immune cell distribution in UC patients. Methods We included 30 UC patients (53% male, median age 42 years) who started a biological or small molecule. Before the first drug administration, mucosal colonic biopsies and a peripheral blood sample were obtained. At the end of induction, colonic biopsies and peripheral blood were sampled again. Patients starting adalimumab (n=2), infliximab (n=3), vedolizumab (n=11), ustekinumab (n=6), ozanimod (n=2) and the JAK inhibitors filgotinib (n=3) and tofacitinib (n=3) were included. Endoscopic improvement was defined as a Mayo endoscopic subscore of 0-1 at the end of induction. From the biopsies, a single-cell suspension was made. Intestinal and circulating immune cells were characterized via flow cytometry. Statistical analysis was performed using a paired t-test. Results Independent of the mechanism of action (MOA), patients responding to therapy showed a decrease of colonic granulocytes (neutrophils (p&lt;0.0001) (Figure 1A), basophils (p&lt;0.0001) (Figure 1B) and eosinophils (p=0.008) (Figure 1C)), active eosinophils (p=0.002) (Figure 1D)), B cells (p=0.05) (Figure 1E), regulatory T cells (p&lt;0.0001) (Figure 1F) and T helper (Th) 2 cells (p=0.02) (Figure 1G), balanced with an increase of Th1 cells (p=0.03) (Figure 1H). In peripheral blood, eosinophils increased in patients not responding to therapy (p=0.05) (Figure 1I). Furthermore, we observed that only patients starting vedolizumab (n=11) showed a decrease in colonic eosinophils (p=0.02) (Figure 1J), active eosinophils (p=0.002) (Figure 1K), B cells (p=0.03) (Figure 1L) and T cells (p=0.004) (Figure 1M). Considering only non-vedolizumab patients (n=19), we did not observe this effect. Conclusion UC patients responding to advanced therapies showed a different intestinal immune cell distribution compared to non-responders, regardless of MOA. Vedolizumab therapy furthermore decreased several mucosal immune cell subsets that migrate to the gut through α4β7-MAdCAM-1 binding. While the effect of vedolizumab on B cells and T cells was previously described, we have now potentially identified an additional eosinophil-reducing effect in the colon.","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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