Pub Date : 2024-01-24DOI: 10.1093/ecco-jcc/jjad212.1330
D G Ribaldone, C Cafasso, M Antonucci, A Palermiti, G P Caviglia, M Vernero, A D'Avolio, J Cusato
Background Vitamin D (VD) is a fat-soluble vitamin essential for calcium homeostasis and that acts at the extraskeletal level. UVB skin exposure allows the synthesis of provitamin D. This undergoes a first hydroxylation in the leaver by the CYP2R1 enzyme and a second hydroxylation in the kidney by the CYP27B1 enzyme: active VD is obtained. VD is transported into the circulation by VDBP and exerts its activity in the target cells binding its VDR receptor. Finally, VD is inactivated by the renal enzyme CYP24A1. Perianal disease (pCD) is a severe phenotypic manifestation of CD that may present as perianal fistula, abscess, recto-vaginal fistula, or stenosis. Among the mechanisms involved in its pathogenesis we recognise local inflammation and intestinal microbiota alteration. Vitamin D (VD) seems to act on these elements. As there are currently no studies on this subject in the literature, the aim of this study is to evaluate the presence of an association between SNPs of genes coding for enzymes, transporters and receptors involved in the VD pathway and the occurrence of pCD in CD patients. Methods The study was carried out on the biological samples of 206 patients with CD, including 34 with pCD, who were followed up at the inflammatory bowel disease clinic in Turin, Italy. Through the use of Real-Time PCR, the genotype distribution of the following genes were assessed: VDR, CYP27B1, CYP24A1, and GC. For the association study, chi-square test was performed with calculation of p value and, when significant, logistic regression and calculation of OR with 95% CI was performed. Results Studying the association between SNPs and the presence of pCD, the following results were obtained: BsmI p=0.0470 and Apal p=0.0251. For BsmI heterozygous genotype there was an OR=2.5 (95% CI 1.2-5.3) of developing perianal disease and p value=0.02, while for ApaI heterozygous there was OR=2.91 (95% CI 1.3-6.6) of presenting pCD, with p value=0.01. Conclusion In the literature, there are several studies examining the association between the heterozygous Aa genotypes of ApaI and Bb genotypes of BsmI and increased inflammatory markers. In addition, some studies suggest that these two genotypes represent a risk factor for some diseases, including multiple myeloma, systemic lupus erythematosus, and mild cognitive disorder. This study demonstrates for the first time an impact of polymorphisms of genes associated with the VD pathway in predicting the onset of pCD. Specifically, the presence of the heterozygous genotype of BsmI and ApaI significantly increases the risk. Future studies need to be performed in different and larger cohorts of patients in order to confirm these data.
背景 维生素 D（VD）是一种脂溶性维生素，是钙平衡所必需的，在骨骼外发挥作用。维生素 D 通过 CYP2R1 酶在体内进行第一次羟化，再通过 CYP27B1 酶在肾脏进行第二次羟化，从而获得活性维生素 D。VD 通过 VDBP 转运进入血液循环，并结合其 VDR 受体在靶细胞中发挥活性。最后，VD 被肾脏酶 CYP24A1 灭活。肛周疾病（pCD）是 CD 的一种严重表型表现，可表现为肛周瘘管、脓肿、直肠阴道瘘或狭窄。其发病机制包括局部炎症和肠道微生物群改变。维生素 D（VD）似乎对这些因素起作用。由于目前还没有这方面的文献研究，本研究旨在评估参与 VD 通路的酶、转运体和受体编码基因的 SNPs 与 CD 患者 pCD 发生之间是否存在关联。方法 该研究对意大利都灵炎症性肠病诊所随访的 206 名 CD 患者（包括 34 名 pCD 患者）的生物样本进行了分析。通过实时 PCR 技术，对以下基因的基因型分布进行了评估：VDR、CYP27B1、CYP24A1 和 GC。在关联研究中，进行了卡方检验并计算了 p 值，如果显著，则进行了逻辑回归并计算了 OR 和 95% CI。结果 在研究 SNP 与 pCD 存在之间的关联时，得出了以下结果：BsmI p=0.0470，Apal p=0.0251。BsmI 杂合基因型的肛周疾病发病率为 OR=2.5（95% CI 1.2-5.3），P 值=0.02；而 ApaI 杂合基因型的肛周疾病发病率为 OR=2.91（95% CI 1.3-6.6），P 值=0.01。结论 在文献中，有多项研究探讨了 ApaI 的杂合 Aa 基因型和 BsmI 的杂合 Bb 基因型与炎症标志物增加之间的关联。此外，一些研究表明，这两种基因型是某些疾病的风险因素，包括多发性骨髓瘤、系统性红斑狼疮和轻度认知障碍。本研究首次证明了与 VD 通路相关的基因多态性对预测 pCD 发病的影响。具体来说，BsmI 和 ApaI 的杂合基因型会显著增加发病风险。未来的研究需要在不同和更大的患者群中进行，以证实这些数据。
{"title":"P1200 Study of correlation between polymorphisms of vitamin D metabolism genes and perianal disease in Crohn's disease","authors":"D G Ribaldone, C Cafasso, M Antonucci, A Palermiti, G P Caviglia, M Vernero, A D'Avolio, J Cusato","doi":"10.1093/ecco-jcc/jjad212.1330","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1330","url":null,"abstract":"Background Vitamin D (VD) is a fat-soluble vitamin essential for calcium homeostasis and that acts at the extraskeletal level. UVB skin exposure allows the synthesis of provitamin D. This undergoes a first hydroxylation in the leaver by the CYP2R1 enzyme and a second hydroxylation in the kidney by the CYP27B1 enzyme: active VD is obtained. VD is transported into the circulation by VDBP and exerts its activity in the target cells binding its VDR receptor. Finally, VD is inactivated by the renal enzyme CYP24A1. Perianal disease (pCD) is a severe phenotypic manifestation of CD that may present as perianal fistula, abscess, recto-vaginal fistula, or stenosis. Among the mechanisms involved in its pathogenesis we recognise local inflammation and intestinal microbiota alteration. Vitamin D (VD) seems to act on these elements. As there are currently no studies on this subject in the literature, the aim of this study is to evaluate the presence of an association between SNPs of genes coding for enzymes, transporters and receptors involved in the VD pathway and the occurrence of pCD in CD patients. Methods The study was carried out on the biological samples of 206 patients with CD, including 34 with pCD, who were followed up at the inflammatory bowel disease clinic in Turin, Italy. Through the use of Real-Time PCR, the genotype distribution of the following genes were assessed: VDR, CYP27B1, CYP24A1, and GC. For the association study, chi-square test was performed with calculation of p value and, when significant, logistic regression and calculation of OR with 95% CI was performed. Results Studying the association between SNPs and the presence of pCD, the following results were obtained: BsmI p=0.0470 and Apal p=0.0251. For BsmI heterozygous genotype there was an OR=2.5 (95% CI 1.2-5.3) of developing perianal disease and p value=0.02, while for ApaI heterozygous there was OR=2.91 (95% CI 1.3-6.6) of presenting pCD, with p value=0.01. Conclusion In the literature, there are several studies examining the association between the heterozygous Aa genotypes of ApaI and Bb genotypes of BsmI and increased inflammatory markers. In addition, some studies suggest that these two genotypes represent a risk factor for some diseases, including multiple myeloma, systemic lupus erythematosus, and mild cognitive disorder. This study demonstrates for the first time an impact of polymorphisms of genes associated with the VD pathway in predicting the onset of pCD. Specifically, the presence of the heterozygous genotype of BsmI and ApaI significantly increases the risk. Future studies need to be performed in different and larger cohorts of patients in order to confirm these data.","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":"139559499","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 : 2024-01-01DOI: 10.1093/ecco-jcc/jjad212.1077
N. Fliss Isakov, C. Seidenberg, D. Meiri, M. Yackobovitch-Gavan, N. Maharshak, A. Hirsch
Medical cannabis (MC) is prescribed to improve appetite and nutritional status in patients with inflammatory bowel diseases (IBD) despite no supporting evidence. We aimed to describe the effect of MC on appetite and dietary intake among patients with IBD. An observational prospective cohort study, among patients with IBD, initiating treatment with MC for disease related symptoms, at the IBD clinic of a tertiary referral medical center. Patients' demographics, anthropometric measurements, medical history, cannabis use history, and medical treatment were documented and an appetite questionnaire (SNAQ), and food frequency questionnaire (FFQ) were filled before MC initiation and throughout 6 months of treatment. Of patients enrolled in the study (n=149, age 39.0±14.1 years, 42.3% female) and treated with MC for disease related symptoms, on top of their routine therapy regimen, while 33.6% received MC for increasing appetite and improving nutritional status. Among patients treated for raising appetite and improving nutritional status, 34.0% experienced a significant increase in appetite after 3 months. None the less, all patients experienced a modest increase in appetite (P<0.05), a trend which was more profound among patients treated with high THC/CBD ratio (SNAQ score 27.0±4.1 at 3 months vs. 25.2±3.6 at baseline, P=0.021). Nonetheless, this increase in appetite throughout the study did not result in increased energy, macronutrient intake or in BMI following MC treatment. Among patients without a significant increase in appetite by 3 months of MC therapy, a significant decrease in BMI was noticed at 6 months (24.1±3.7 at baseline vs. 23.4±3.6 at 6 months, Pv=0.010). Use of MC, and specifically THC, may be a potential strategy to improve appetite among some patients with IBD. This increase in appetite was not associated with an increase in caloric intake or in BMI at follow-up.
尽管没有证据证明医用大麻（MC）可改善炎症性肠病（IBD）患者的食欲和营养状况，但仍有处方医用大麻用于改善患者的食欲和营养状况。我们旨在描述医用大麻对 IBD 患者食欲和饮食摄入的影响。 我们在一家三级转诊医疗中心的 IBD 诊所对因疾病相关症状而开始接受 MC 治疗的 IBD 患者进行了一项前瞻性队列观察研究。研究记录了患者的人口统计学特征、人体测量数据、病史、大麻使用史和治疗情况，并在开始使用 MC 之前和整个 6 个月的治疗期间填写了食欲问卷（SNAQ）和食物频率问卷（FFQ）。 参与研究的患者（人数=149，年龄（39.0±14.1）岁，42.3%为女性）中，除常规治疗外，还有33.6%的患者因疾病相关症状而接受MC治疗，以提高食欲和改善营养状况。在接受提高食欲和改善营养状况治疗的患者中，34.0%的患者在 3 个月后食欲明显增加。尽管如此，所有患者的食欲都略有增加（P<0.05），这一趋势在接受高 THC/CBD 比率治疗的患者中更为明显（3 个月时的 SNAQ 评分为 27.0±4.1 vs. 基线时的 25.2±3.6，P=0.021）。然而，在整个研究过程中，食欲的增加并没有导致能量、宏量营养素摄入的增加，也没有导致 MC 治疗后体重指数的增加。在接受 MC 治疗 3 个月后食欲没有明显增加的患者中，6 个月时体重指数明显下降（基线为 24.1±3.7 vs. 6 个月时为 23.4±3.6，Pv=0.010）。 使用MC，特别是THC，可能是改善部分IBD患者食欲的一种潜在策略。食欲的增加与随访时热量摄入或体重指数的增加无关。
{"title":"P947 medical cannabis increases appetite but not body weight in patients with inflammatory bowel diseases","authors":"N. Fliss Isakov, C. Seidenberg, D. Meiri, M. Yackobovitch-Gavan, N. Maharshak, A. Hirsch","doi":"10.1093/ecco-jcc/jjad212.1077","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1077","url":null,"abstract":"\u0000 \u0000 \u0000 Medical cannabis (MC) is prescribed to improve appetite and nutritional status in patients with inflammatory bowel diseases (IBD) despite no supporting evidence. We aimed to describe the effect of MC on appetite and dietary intake among patients with IBD.\u0000 \u0000 \u0000 \u0000 An observational prospective cohort study, among patients with IBD, initiating treatment with MC for disease related symptoms, at the IBD clinic of a tertiary referral medical center. Patients' demographics, anthropometric measurements, medical history, cannabis use history, and medical treatment were documented and an appetite questionnaire (SNAQ), and food frequency questionnaire (FFQ) were filled before MC initiation and throughout 6 months of treatment.\u0000 \u0000 \u0000 \u0000 Of patients enrolled in the study (n=149, age 39.0±14.1 years, 42.3% female) and treated with MC for disease related symptoms, on top of their routine therapy regimen, while 33.6% received MC for increasing appetite and improving nutritional status. Among patients treated for raising appetite and improving nutritional status, 34.0% experienced a significant increase in appetite after 3 months. None the less, all patients experienced a modest increase in appetite (P<0.05), a trend which was more profound among patients treated with high THC/CBD ratio (SNAQ score 27.0±4.1 at 3 months vs. 25.2±3.6 at baseline, P=0.021). Nonetheless, this increase in appetite throughout the study did not result in increased energy, macronutrient intake or in BMI following MC treatment. Among patients without a significant increase in appetite by 3 months of MC therapy, a significant decrease in BMI was noticed at 6 months (24.1±3.7 at baseline vs. 23.4±3.6 at 6 months, Pv=0.010).\u0000 \u0000 \u0000 \u0000 Use of MC, and specifically THC, may be a potential strategy to improve appetite among some patients with IBD. This increase in appetite was not associated with an increase in caloric intake or in BMI at follow-up.\u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631126","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 : 2024-01-01DOI: 10.1093/ecco-jcc/jjad212.1080
P. Dhoble, D. Desai, P. Abraham, T. Gupta, V. Dharap, M. Kutar
Most of the nutritional assessment tools assess only nutrition. The Malnutrition Inflammation Risk Tool (MIRT) incorporates both malnutrition and inflammation (CRP).1 However, CRP is a less sensitive biomarker than fecal calprotectin for the assessment of inflammation. Adding fecal calprotectin (FC) in the MIRT score may improve the assessment of malnutrition risk. FC level cutoff of < 250 mg/kg in adults correlate with endoscopic remission with good sensitivity and specificity.2 Fecal calprotectin level greater than 800 µg/g is predictive of a need for rescue therapy.3 To study if adding fecal calprotectin to CRP by improves the yield of MIRT score This is a single center, prospective, cohort study including consecutive patients with IBD (Ulcerative colitis {UC} and Crohn’s disease {CD}). Malnutrition was defined as per European society for clinical nutrition and metabolism (ESPEN guidelines): BMI <18.5 kg/m2 or unintentional weight loss >10% (indefinite time). MIRT score was calculated with BMI, weight loss and CRP and MIRT-FC by adding FC to CRP with as shown in the table below: During 2019 to 2021, 200 patients included, median age 39 years (IQR 28-53) (105 UC, 93 CD and 2 IBD-U), 60 (30%) patients had malnutrition (32 UC, 26 CD and 2 IBD-U and 27 (45%) malnourished IBD patients had MIRT score > 3. CRP values were normal in 30 (50%). Adding fecal calprotectin to MIRT score malnourished IBD patients, 46 (76%) malnourished IBD patients had MIRT score > 3 (P=0.005). This modification (MIRT FC) increased the yield of existing MIRT score by 31%. MIRT-FC score improved the yield of MIRT score. Prospective studies are required to validate this further. References: 1. Jansen I, Prager M, Valentini L, Büning C. Inflammation-driven malnutrition: a new screening tool predicts outcome in Crohn’s disease. British Journal of Nutrition. Cambridge University Press; 2016;116(6):1061–7. 2. D'Haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012; 18:2218-2224. 3. Sasidharan S, Sasson AN, Shannon KM, Ananthakrishnan AN. Fecal Calprotectin Is a Predictor of Need for Rescue Therapy in Hospitalized Severe Colitis. Inflamm Bowel Dis. 2022;28(12):1833-1837.
大多数营养评估工具只评估营养状况。营养不良炎症风险工具（MIRT）包含营养不良和炎症（CRP）1。然而，在炎症评估方面，CRP 是一种灵敏度低于粪便热保护蛋白的生物标志物。在 MIRT 评分中加入粪便钙蛋白（FC）可改善对营养不良风险的评估。3 目的：研究在 CRP 的基础上添加粪便钙蛋白是否能提高 MIRT 评分的准确性。营养不良的定义符合欧洲临床营养与代谢学会（ESPEN）指南：体重指数为 10%（不定期）。MIRT 评分通过 BMI、体重减轻和 CRP 计算得出，MIRT-FC 通过将 FC 与 CRP 相加计算得出，如下表所示： 在 2019 年至 2021 年期间，共纳入 200 例患者，中位年龄为 39 岁（IQR 28-53）（105 例 UC、93 例 CD 和 2 例 IBD-U），60 例（30%）患者营养不良（32 例 UC、26 例 CD 和 2 例 IBD-U），27 例（45%）营养不良的 IBD 患者 MIRT 评分大于 3。30名（50%）患者的 CRP 值正常。在营养不良 IBD 患者的 MIRT 评分中加入粪便钙蛋白，46 例（76%）营养不良 IBD 患者的 MIRT 评分大于 3（P=0.005）。这一修改（MIRT FC）将现有 MIRT 评分的收益率提高了 31%。 MIRT-FC 评分提高了 MIRT 评分的得分率。需要进行前瞻性研究来进一步验证。参考文献1.Jansen I、Prager M、Valentini L、Büning C.炎症驱动的营养不良：预测克罗恩病预后的新筛查工具。英国营养学杂志》。剑桥大学出版社；2016；116（6）：1061-7。2.D'Haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease.Inflamm Bowel Dis 2012; 18:2218-2224.3.Sasidharan S, Sasson AN, Shannon KM, Ananthakrishnan AN.粪便钙蛋白是住院重症结肠炎患者是否需要抢救治疗的预测因子》（Fecal Calprotectin Is a Predictor of Need for Rescue Therapy in Hospitalized Severe Colitis.Inflamm Bowel Dis.2022;28(12):1833-1837.
{"title":"P950 Advancing Precision Nutritional Assessment in Inflammatory Bowel Disease (IBD): Adding Fecal Calprotectin in the Malnutrition Inflammation Risk Tool (MIRT) score","authors":"P. Dhoble, D. Desai, P. Abraham, T. Gupta, V. Dharap, M. Kutar","doi":"10.1093/ecco-jcc/jjad212.1080","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1080","url":null,"abstract":"\u0000 \u0000 \u0000 Most of the nutritional assessment tools assess only nutrition. The Malnutrition Inflammation Risk Tool (MIRT) incorporates both malnutrition and inflammation (CRP).1 However, CRP is a less sensitive biomarker than fecal calprotectin for the assessment of inflammation. Adding fecal calprotectin (FC) in the MIRT score may improve the assessment of malnutrition risk. FC level cutoff of < 250 mg/kg in adults correlate with endoscopic remission with good sensitivity and specificity.2 Fecal calprotectin level greater than 800 µg/g is predictive of a need for rescue therapy.3\u0000 \u0000 \u0000 \u0000 To study if adding fecal calprotectin to CRP by improves the yield of MIRT score\u0000 \u0000 \u0000 \u0000 This is a single center, prospective, cohort study including consecutive patients with IBD (Ulcerative colitis {UC} and Crohn’s disease {CD}). Malnutrition was defined as per European society for clinical nutrition and metabolism (ESPEN guidelines): BMI <18.5 kg/m2 or unintentional weight loss >10% (indefinite time). MIRT score was calculated with BMI, weight loss and CRP and MIRT-FC by adding FC to CRP with as shown in the table below:\u0000 \u0000 \u0000 \u0000 During 2019 to 2021, 200 patients included, median age 39 years (IQR 28-53) (105 UC, 93 CD and 2 IBD-U), 60 (30%) patients had malnutrition (32 UC, 26 CD and 2 IBD-U and 27 (45%) malnourished IBD patients had MIRT score > 3. CRP values were normal in 30 (50%). Adding fecal calprotectin to MIRT score malnourished IBD patients, 46 (76%) malnourished IBD patients had MIRT score > 3 (P=0.005). This modification (MIRT FC) increased the yield of existing MIRT score by 31%.\u0000 \u0000 \u0000 \u0000 MIRT-FC score improved the yield of MIRT score. Prospective studies are required to validate this further.\u0000 References:\u0000 1. Jansen I, Prager M, Valentini L, Büning C. Inflammation-driven malnutrition: a new screening tool predicts outcome in Crohn’s disease. British Journal of Nutrition. Cambridge University Press; 2016;116(6):1061–7.\u0000 2. D'Haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012; 18:2218-2224.\u0000 3. Sasidharan S, Sasson AN, Shannon KM, Ananthakrishnan AN. Fecal Calprotectin Is a Predictor of Need for Rescue Therapy in Hospitalized Severe Colitis. Inflamm Bowel Dis. 2022;28(12):1833-1837.\u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631198","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 : 2024-01-01DOI: 10.1093/ecco-jcc/jjad212.1191
G. Raphael, G. Damera, T. Angeles, S. Li, S. Stoyanov
TEV-48574 is a human antibody that targets tumor necrosis factor (TNF)-like ligand 1A, also known as TNF superfamily member 15 (TNFSF15). It is in clinical development as a potential treatment for ulcerative colitis (UC) and Crohn’s disease (CD). TL1A signalling is believed to amplify immune-mediated inflammation in asthma and inflammatory bowel disease (IBD); thus, targeting TL1A may mitigate over-activation of immune responses. A proof-of-concept phase 2A study evaluated safety, tolerability and efficacy of TEV-48574 as treatment for adults with severe uncontrolled asthma (Clinicaltrials.gov NCT04545385). Although the study terminated (after meeting pre-specified criteria for futility at a preplanned interim analysis) the drug demonstrated favourable safety, tolerability and immunogenicity data, supporting the potential use of anti-TL1A treatment in patients with UC and CD. TEV-48574 was administered as a loading dose followed by 7 maintenance doses given subcutaneously (sc) every 2 weeks for 16 weeks in adult patients (n = 65) with severe T2-low asthma with no/low inflammation at baseline. The primary efficacy endpoint was reduction in patients who experience loss of asthma control (LoAC). Patients were monitored for LoAC at bi-weekly visits and daily by use of a handheld spirometer/e-diary. Safety was assessed throughout the study. Of 65 randomized patients, 64 received at least one dose of study drug and were included in the safety analysis (33 active drug; 31 placebo). There were no severe AEs, treatment related SAEs, deaths, or withdrawals due to adverse events, and no medical device-related issues. There were no clinically meaningful changes in lab parameters, vital signs or ECGs. Furthermore, there was no evidence of immune suppression, opportunistic infections, or malignancies. Mild treatment-related adverse reactions occurred in both treatment groups (erythema and pruritus in two placebo patients; erythema in one TEV-48574 treated patient). Mild injection site reactions occurred more frequently (not statistically different) in the TEV-48574 group. Treatment-emergent anti-drug antibodies were reported in patients taking TEV-48574 (3 patients; 9.09%), with no anaphylactic or severe systemic reactions. Overall, TEV-48574 administered every 2 weeks over 16 weeks demonstrated a favourable safety and tolerability profile with no emerging safety signals or evidence of immunosuppression. This is consistent with TL1A being an amplifier of inflammation. Treatment with TEV-48574 may dampen excessive inflammation without inducing a state of immunodeficiency in patients with conditions such as UC or CD, supporting further development in these indications.
{"title":"P1061 TEV-48574, an anti-TL1A antibody in development for use in IBD, is safe and well tolerated following 16 weeks of subcutaneous treatment in adults with severe uncontrolled T2-low/non T2 asthma","authors":"G. Raphael, G. Damera, T. Angeles, S. Li, S. Stoyanov","doi":"10.1093/ecco-jcc/jjad212.1191","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1191","url":null,"abstract":"\u0000 \u0000 \u0000 TEV-48574 is a human antibody that targets tumor necrosis factor (TNF)-like ligand 1A, also known as TNF superfamily member 15 (TNFSF15). It is in clinical development as a potential treatment for ulcerative colitis (UC) and Crohn’s disease (CD). TL1A signalling is believed to amplify immune-mediated inflammation in asthma and inflammatory bowel disease (IBD); thus, targeting TL1A may mitigate over-activation of immune responses. A proof-of-concept phase 2A study evaluated safety, tolerability and efficacy of TEV-48574 as treatment for adults with severe uncontrolled asthma (Clinicaltrials.gov NCT04545385). Although the study terminated (after meeting pre-specified criteria for futility at a preplanned interim analysis) the drug demonstrated favourable safety, tolerability and immunogenicity data, supporting the potential use of anti-TL1A treatment in patients with UC and CD.\u0000 \u0000 \u0000 \u0000 TEV-48574 was administered as a loading dose followed by 7 maintenance doses given subcutaneously (sc) every 2 weeks for 16 weeks in adult patients (n = 65) with severe T2-low asthma with no/low inflammation at baseline. The primary efficacy endpoint was reduction in patients who experience loss of asthma control (LoAC). Patients were monitored for LoAC at bi-weekly visits and daily by use of a handheld spirometer/e-diary. Safety was assessed throughout the study.\u0000 \u0000 \u0000 \u0000 Of 65 randomized patients, 64 received at least one dose of study drug and were included in the safety analysis (33 active drug; 31 placebo). There were no severe AEs, treatment related SAEs, deaths, or withdrawals due to adverse events, and no medical device-related issues. There were no clinically meaningful changes in lab parameters, vital signs or ECGs. Furthermore, there was no evidence of immune suppression, opportunistic infections, or malignancies. Mild treatment-related adverse reactions occurred in both treatment groups (erythema and pruritus in two placebo patients; erythema in one TEV-48574 treated patient). Mild injection site reactions occurred more frequently (not statistically different) in the TEV-48574 group. Treatment-emergent anti-drug antibodies were reported in patients taking TEV-48574 (3 patients; 9.09%), with no anaphylactic or severe systemic reactions.\u0000 \u0000 \u0000 \u0000 Overall, TEV-48574 administered every 2 weeks over 16 weeks demonstrated a favourable safety and tolerability profile with no emerging safety signals or evidence of immunosuppression. This is consistent with TL1A being an amplifier of inflammation. Treatment with TEV-48574 may dampen excessive inflammation without inducing a state of immunodeficiency in patients with conditions such as UC or CD, supporting further development in these indications.\u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631418","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 : 2024-01-01DOI: 10.1093/ecco-jcc/jjad212.0480
A. Vernon-Roberts, P. Chan, B. Christensen, R. Havrlant, E. Giles, A. Williams
The incidence of paediatric inflammatory bowel disease (IBD) is rising, and as such there is an increasing need to support adolescents with IBD as they from transition from paediatric to adult care. The use of a structured process for transition is well supported in the literature, however, variation in the delivery of transitional care for adolescents with IBD has been identified across Australis and New Zealand. The aim of this study was to develop consensus statements, based on evidence and expert opinion, to guide transitional care services in IBD. The consensus statements were developed using a modified UCLA-RAND methodology. An IBD expert steering committee was formed, and then a systematic literature review conducted to grade the available evidence and inform initial development of consensus statements. A multi-disciplinary group was formed comprising 16 participants [clinicians, nurses, surgeons, psychologists], that voted anonymously on the level of appropriateness and necessity for each consensus statement, as well as provided general feedback for each. Scoring was facilitated using Likert scales [1=lowest, 9=highest] with a median ≥7 required for inclusion. Fourteen consensus statements were devised by the Steering committee (Table 1). Key recommendations including the use of a structured transition programme and transition coordinator. Statements recommended assessment of mental health and transition readiness, and outlined discussion points regarding lifestyle, environment and psychosocial factors to be held with adolescents. The importance of allied health input, the age for transition, recommendations for clinical communication and handover were highlighted, as well as considerations for individual patients. In the first voting round by the multi-disciplinary group each statement reached a median score of ≥ 8 for appropriateness, and ≥7 for necessity. An online meeting with both groups was held to discuss voting results and refine statements. Table 1. Final consensus statements to guide transition of children with inflammatory bowel disease in Australasia. There is an identified need for guidance in paediatric to adult transitional care for adolescents with IBD. Consensus statements were developed by a multi-disciplinary group, supported by published evidence, to provide this guidance. The planned publication of the consensus process and statements will facilitate standardize delivery of IBD transitional care within Australasia.
{"title":"P350 Development of consensus statements for transitional care for adolescents with Inflammatory bowel disease throughout Australia and New Zealand","authors":"A. Vernon-Roberts, P. Chan, B. Christensen, R. Havrlant, E. Giles, A. Williams","doi":"10.1093/ecco-jcc/jjad212.0480","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0480","url":null,"abstract":"\u0000 \u0000 \u0000 The incidence of paediatric inflammatory bowel disease (IBD) is rising, and as such there is an increasing need to support adolescents with IBD as they from transition from paediatric to adult care. The use of a structured process for transition is well supported in the literature, however, variation in the delivery of transitional care for adolescents with IBD has been identified across Australis and New Zealand. The aim of this study was to develop consensus statements, based on evidence and expert opinion, to guide transitional care services in IBD.\u0000 \u0000 \u0000 \u0000 The consensus statements were developed using a modified UCLA-RAND methodology. An IBD expert steering committee was formed, and then a systematic literature review conducted to grade the available evidence and inform initial development of consensus statements. A multi-disciplinary group was formed comprising 16 participants [clinicians, nurses, surgeons, psychologists], that voted anonymously on the level of appropriateness and necessity for each consensus statement, as well as provided general feedback for each. Scoring was facilitated using Likert scales [1=lowest, 9=highest] with a median ≥7 required for inclusion.\u0000 \u0000 \u0000 \u0000 Fourteen consensus statements were devised by the Steering committee (Table 1). Key recommendations including the use of a structured transition programme and transition coordinator. Statements recommended assessment of mental health and transition readiness, and outlined discussion points regarding lifestyle, environment and psychosocial factors to be held with adolescents. The importance of allied health input, the age for transition, recommendations for clinical communication and handover were highlighted, as well as considerations for individual patients. In the first voting round by the multi-disciplinary group each statement reached a median score of ≥ 8 for appropriateness, and ≥7 for necessity. An online meeting with both groups was held to discuss voting results and refine statements.\u0000 Table 1. Final consensus statements to guide transition of children with inflammatory bowel disease in Australasia.\u0000 \u0000 \u0000 \u0000 \u0000 There is an identified need for guidance in paediatric to adult transitional care for adolescents with IBD. Consensus statements were developed by a multi-disciplinary group, supported by published evidence, to provide this guidance. The planned publication of the consensus process and statements will facilitate standardize delivery of IBD transitional care within Australasia.\u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631470","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 : 2024-01-01DOI: 10.1093/ecco-jcc/jjad212.0696
O. Atia, Z. Shavit-Brunschwig, G. Focht, R. Lev-Tzion, R. Stein, E. Broide, D. Urlep, J. Hyams, B. Weiss, M. Aloi, A. Assa, R. Russell, D. Turner
Prospective long-term data on vedolizumab (VDZ) in children with Crohn’s disease (CD) and ulcerative colitis (UC) are lacking. In this prospective, multicenter cohort study, we aimed to evaluate the effectiveness and safety of maintenance therapy with VDZ in pediatric CD and UC. Children commenced on VDZ were followed at baseline and 2, 6, 14, 30 and 54 weeks thereafter. Serum for drug levels and stool for calprotectin were repeatedly obtained. The primary outcome was sustained steroid-free remission (SSFR), defined as clinical remission )PUCAI<10 or wPCDAI<12.5) without steroids/EEN at both 30 and 54 weeks, analyzed under the ITT principle. 139 children were enrolled (77 [55%] UC, 62 [45%] CD; age 14.9 years (IQR 12.0-16.6). Of the 119 (86%) children >30kg, 110 (92%) received a dose of 300mg; 20 (14%) weighed<30 kg and received a dose of 8.3mg/kg (IQR 7–10.3). Week-54 remission rate was 52% in UC and 37% in CD; SSFR rates were 42% and 24%, respectively (OR 2.2 [95%CI 1.1-4.7] Figure). SSFR rate was numerically higher in isolated colonic CD than in ileal disease (5/11 [45%] vs 10/49 [20%], OR 3.3 [95%CI 0.8-12.9]; p=0.08). Infusion interval was shortened in 22 children (10 [13%] UC, 12 [19%] CD), of whom none achieved SSFR. SSFR rate was higher in week-6 responders compared to non-responders in UC (51% vs 27%, OR 2.9 [1.1-7.7]) and CD (35% vs 14%, OR 3.4 [95%CI 0.95-12.4]), similar to the week-14 figures (UC: 50% vs 22%, OR 3.6 [1.2-11.1]; CD: 36% vs 8%, OR 6.2 [1.3-30.8]). SSFR was eventually achieved in 49% of UC children having mild disease at week-6 and 14% with moderate-severe disease (OR 5.8 [95%CI 1.2-28.2]); the corresponding rates in CD were 31% and 0% (p=0.02). In multivariable models, the best predictors in CD were lower wPCDAI at baseline (AUROC 0.88 [95%CI 0.79-0.96]; optimal cutoff 25 (sens/spec 76%/80%)) and at week 6 (0.90 [0.82-0.98]; optimal cutoff 17.5 (80%/87%)). In UC, the best predictors were PUCAI at week 6 (0.70 [0.57-0.82]; optimal cutoff 10 (64%/57%)) and at week-14 (0.78 [0.67-0.89]; optimal cutoff 5 (76%/60%; Table). In children <30kg, SSFR was associated with week 6 drug levels >30ug/mL, not reaching statistical significance (3/6 [50%] vs 1/8 [13%], OR 7.0 [95%CI 0.5-97]). By week 54, 197 adverse events were recorded, of which were VDZ-related in 8 (5.8%) children, and in 2 (1.4%) led to stopping VDZ; none were severe. There was 1 lymphoma case judged to be unrelated to VDZ. VDZ was effective for maintaining remission, more so in UC and in colonic CD. The likelihood of eventually achieving SSFR was very low in children with moderate-severe disease or those not showing response at week-6, particularly in CD.
目前还缺乏有关维多珠单抗（VDZ）在克罗恩病（CD）和溃疡性结肠炎（UC）患儿中的长期前瞻性数据。在这项前瞻性多中心队列研究中，我们旨在评估VDZ在儿童克罗恩病和溃疡性结肠炎维持治疗中的有效性和安全性。 我们对开始使用 VDZ 的儿童进行了基线随访，并在此后的 2、6、14、30 和 54 周进行了随访。反复采集血清检测药物水平和粪便检测钙蛋白。主要结果是持续无类固醇缓解（SSFR），定义为临床缓解 )PUCAI30公斤，110人（92%）接受了300毫克的剂量；20人（14%）称重30ug/mL，未达到统计学意义（3/6 [50%] vs 1/8 [13%]，OR 7.0 [95%CI 0.5-97]）。截至第54周，共记录了197例不良事件，其中8例（5.8%）儿童的不良事件与VDZ有关，2例（1.4%）导致停用VDZ；无严重不良事件。有1例淋巴瘤病例被判定与VDZ无关。 VDZ 对维持缓解有效，对 UC 和结肠 CD 更有效。中度重症患儿或在第 6 周时未显示出反应的患儿最终达到 SSFR 的可能性非常低，尤其是 CD 患儿。
{"title":"P566 Maintenance vedolizumab treatment in pediatric IBD: 54-week follow-up of the prospective multicenter VEDOKIDS study","authors":"O. Atia, Z. Shavit-Brunschwig, G. Focht, R. Lev-Tzion, R. Stein, E. Broide, D. Urlep, J. Hyams, B. Weiss, M. Aloi, A. Assa, R. Russell, D. Turner","doi":"10.1093/ecco-jcc/jjad212.0696","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0696","url":null,"abstract":"\u0000 \u0000 \u0000 Prospective long-term data on vedolizumab (VDZ) in children with Crohn’s disease (CD) and ulcerative colitis (UC) are lacking. In this prospective, multicenter cohort study, we aimed to evaluate the effectiveness and safety of maintenance therapy with VDZ in pediatric CD and UC.\u0000 \u0000 \u0000 \u0000 Children commenced on VDZ were followed at baseline and 2, 6, 14, 30 and 54 weeks thereafter. Serum for drug levels and stool for calprotectin were repeatedly obtained. The primary outcome was sustained steroid-free remission (SSFR), defined as clinical remission )PUCAI<10 or wPCDAI<12.5) without steroids/EEN at both 30 and 54 weeks, analyzed under the ITT principle.\u0000 \u0000 \u0000 \u0000 139 children were enrolled (77 [55%] UC, 62 [45%] CD; age 14.9 years (IQR 12.0-16.6). Of the 119 (86%) children >30kg, 110 (92%) received a dose of 300mg; 20 (14%) weighed<30 kg and received a dose of 8.3mg/kg (IQR 7–10.3). Week-54 remission rate was 52% in UC and 37% in CD; SSFR rates were 42% and 24%, respectively (OR 2.2 [95%CI 1.1-4.7] Figure). SSFR rate was numerically higher in isolated colonic CD than in ileal disease (5/11 [45%] vs 10/49 [20%], OR 3.3 [95%CI 0.8-12.9]; p=0.08). Infusion interval was shortened in 22 children (10 [13%] UC, 12 [19%] CD), of whom none achieved SSFR.\u0000 SSFR rate was higher in week-6 responders compared to non-responders in UC (51% vs 27%, OR 2.9 [1.1-7.7]) and CD (35% vs 14%, OR 3.4 [95%CI 0.95-12.4]), similar to the week-14 figures (UC: 50% vs 22%, OR 3.6 [1.2-11.1]; CD: 36% vs 8%, OR 6.2 [1.3-30.8]). SSFR was eventually achieved in 49% of UC children having mild disease at week-6 and 14% with moderate-severe disease (OR 5.8 [95%CI 1.2-28.2]); the corresponding rates in CD were 31% and 0% (p=0.02).\u0000 In multivariable models, the best predictors in CD were lower wPCDAI at baseline (AUROC 0.88 [95%CI 0.79-0.96]; optimal cutoff 25 (sens/spec 76%/80%)) and at week 6 (0.90 [0.82-0.98]; optimal cutoff 17.5 (80%/87%)). In UC, the best predictors were PUCAI at week 6 (0.70 [0.57-0.82]; optimal cutoff 10 (64%/57%)) and at week-14 (0.78 [0.67-0.89]; optimal cutoff 5 (76%/60%; Table).\u0000 In children <30kg, SSFR was associated with week 6 drug levels >30ug/mL, not reaching statistical significance (3/6 [50%] vs 1/8 [13%], OR 7.0 [95%CI 0.5-97]). By week 54, 197 adverse events were recorded, of which were VDZ-related in 8 (5.8%) children, and in 2 (1.4%) led to stopping VDZ; none were severe. There was 1 lymphoma case judged to be unrelated to VDZ.\u0000 \u0000 \u0000 \u0000 VDZ was effective for maintaining remission, more so in UC and in colonic CD. The likelihood of eventually achieving SSFR was very low in children with moderate-severe disease or those not showing response at week-6, particularly in CD.\u0000 \u0000 \u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631499","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 : 2024-01-01DOI: 10.1093/ecco-jcc/jjad212.1285
P. Alavi Nejad, M. Mokhtare, F. Farsi, M. Arshadzadeh, S. Shetty, O. Eslami, M. Arefi, M. H. Emara, E. Abdelsameea, J. Rezaei, S. M. A. Alavi, Q. T. Tran, R. Salma, A. Parsi, M. H. Ahmed, A. Monged, A. Quadri, A. Jawad, A. U. Rehman, S. H. Lee, N. S. Behl, E. Ghoneem
The aim of current study is to evaluate impact of COVID19 pandemic and vaccination against it on the course and symptoms of IBD. During a six months’ period, all of the IBD cases who attend in outpatient clinics of nine referral centers in 6 countries include and request to fill a questionnaire about their demographic characters and pattern of IBD, any history of involvement with COVID19 and their vaccination history. overall 812 cases from 16 countries included (52.4% male) with average age of 36.8 y (range 7 – 76). 68.5% of participants diagnosed as UC and 29.5% as CD. 80% of participants have vaccinated against COVID19 (average 2.3 times, range 1 – 5). Among those who vaccinated (group A) 31.6% experienced side effects and complication without any mortality. The most common complications of vaccination include fever (24%), fatigue (20.1%) and anorexia 8.6%. The most common reasons for vaccination refusal (group B) were fear of vaccine complication (55.5%), no believe in vaccine protection (29.6%) and fear of immunocompromised condition (17.9%). In group A overall 61% of participants involved with COVID 19 (36.2% after vaccination) in comparison with 48.1% in group B (P = 0.0052). Most of the involvements in both groups were not sever and just a minority of patients admitted to hospital (10% in group A and 6.4% in group B). Following COVID involvement, 45.1% of cases suffered with GI symptoms (mostly diarrhea (72.5%) and abdominal pain (64.5%)). In group A, 37.3% of involvements have happened before vaccination. Vaccination against COVID19 is safe and effective among IBD patients and following vaccination, most of complications are minor and negligible. In case of COVID involvement, it would not be serious and there is no need to hold the medications. Among IBD patients, the most common reason for vaccination refusal is fear of vaccine side effect.
{"title":"P1155 Impact of COVID19 pandemic and vaccination among IBD patients: a multinational cross sectional survey","authors":"P. Alavi Nejad, M. Mokhtare, F. Farsi, M. Arshadzadeh, S. Shetty, O. Eslami, M. Arefi, M. H. Emara, E. Abdelsameea, J. Rezaei, S. M. A. Alavi, Q. T. Tran, R. Salma, A. Parsi, M. H. Ahmed, A. Monged, A. Quadri, A. Jawad, A. U. Rehman, S. H. Lee, N. S. Behl, E. Ghoneem","doi":"10.1093/ecco-jcc/jjad212.1285","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1285","url":null,"abstract":"\u0000 \u0000 \u0000 The aim of current study is to evaluate impact of COVID19 pandemic and vaccination against it on the course and symptoms of IBD.\u0000 \u0000 \u0000 \u0000 During a six months’ period, all of the IBD cases who attend in outpatient clinics of nine referral centers in 6 countries include and request to fill a questionnaire about their demographic characters and pattern of IBD, any history of involvement with COVID19 and their vaccination history.\u0000 \u0000 \u0000 \u0000 overall 812 cases from 16 countries included (52.4% male) with average age of 36.8 y (range 7 – 76). 68.5% of participants diagnosed as UC and 29.5% as CD. 80% of participants have vaccinated against COVID19 (average 2.3 times, range 1 – 5). Among those who vaccinated (group A) 31.6% experienced side effects and complication without any mortality. The most common complications of vaccination include fever (24%), fatigue (20.1%) and anorexia 8.6%. The most common reasons for vaccination refusal (group B) were fear of vaccine complication (55.5%), no believe in vaccine protection (29.6%) and fear of immunocompromised condition (17.9%). In group A overall 61% of participants involved with COVID 19 (36.2% after vaccination) in comparison with 48.1% in group B (P = 0.0052). Most of the involvements in both groups were not sever and just a minority of patients admitted to hospital (10% in group A and 6.4% in group B). Following COVID involvement, 45.1% of cases suffered with GI symptoms (mostly diarrhea (72.5%) and abdominal pain (64.5%)). In group A, 37.3% of involvements have happened before vaccination.\u0000 \u0000 \u0000 \u0000 Vaccination against COVID19 is safe and effective among IBD patients and following vaccination, most of complications are minor and negligible. In case of COVID involvement, it would not be serious and there is no need to hold the medications. Among IBD patients, the most common reason for vaccination refusal is fear of vaccine side effect.\u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631553","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 : 2024-01-01DOI: 10.1093/ecco-jcc/jjad212.1379
E. De Dycker, S. Vermeire, M. Ferrante, T. Lambrechts, A. Paps, P. Geens, E. Loddewijkx, J. Sabino, T. Hillary, B. Verstockt
Three Janus kinase (JAK) inhibitors, tofacitinib (TFC), filgotinib (FIL) and upadacitinib (UPA), have been approved for treatment of Crohn’s disease (CD) and/or ulcerative colitis (UC). During the IBD registrational trials, acne was reported as adverse event (AE) in 5-7% of UPA treated patients, but not in the FIL and TFC programs. Hence, we assessed the prevalence of JAK inhibitor associated acne in a real-life cohort. All patients initiating JAK inhibitors for active moderate-to-severe CD or UC at our center were included. Patients were prospectively monitored at prespecified timepoints, and specifically assessed for AEs including acne. Affected patients completed a visual analogue scale (VAS) to assess the impact of acne on their quality of life. All pictures of skin lesions were assessed by a dermatologist specialized in inflammatory skin diseases. In total, 46 patients initiated TFC, 40 FIL and 79 UPA. None of the TFC or FIL treated patients reported new onset of acne. Instead, 17 (21.5%) patients (9 CD, 8 UC; median [IQR] age 28.2 [25.2-45.0]; 47.1% female) spontaneously reported acne during UPA therapy. Most (89.5%) reported new onset of acne, while 2 (10.5%) mentioned a deterioration of existing acne during UPA induction. Previous acne during adolescence was reported by 46.2%. Lesions were present in the face (82.3%), back (23.5%), chest (23.5%) and scalp (11.8%). The acne phenotype included inflammatory papules in all patients, but also pustules (66.7%), nodules (33.3%), cysts (11.1%) and comedones (11.1%) were observed. A median VAS score of 5.5 [5.0-7.0] highlighted the impact on the patient’s quality of life, though no patient interrupted UPA due to acne. Six (35.2%) patients were referred to a dermatologist for acne. Most patients (82.4%) received topical skin therapy during UPA induction based on a standard operation procedure approved by the dermatologist and communicated via the IBD nurses. Three patients (17.6%) received antibiotics during UPA induction because of acne. During UPA maintenance, 5 patients (29.4%) reported resolution of skin problems with only 1 requiring continued skin therapy. Ten patients (58.7%) continued topical skin therapy during maintenance, with 4 of them requiring continued antibiotic treatment for at least 3 months. A single patient was deescalated from UPA 30mg to 15mg QD because of severe acne, with little improvement. In this real-world experience, JAK inhibitor associated acne was uniquely linked to UPA, occurring in one fifth of patients. This is more prevalent than observed in the registrational trials. Awareness and patient education are therefore important, as well as early referral to the dermatologist for appropriate treatment.
{"title":"N07 JAKne: JAK inhibitor associated acne, a real-life single-center experience","authors":"E. De Dycker, S. Vermeire, M. Ferrante, T. Lambrechts, A. Paps, P. Geens, E. Loddewijkx, J. Sabino, T. Hillary, B. Verstockt","doi":"10.1093/ecco-jcc/jjad212.1379","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.1379","url":null,"abstract":"\u0000 \u0000 \u0000 Three Janus kinase (JAK) inhibitors, tofacitinib (TFC), filgotinib (FIL) and upadacitinib (UPA), have been approved for treatment of Crohn’s disease (CD) and/or ulcerative colitis (UC). During the IBD registrational trials, acne was reported as adverse event (AE) in 5-7% of UPA treated patients, but not in the FIL and TFC programs. Hence, we assessed the prevalence of JAK inhibitor associated acne in a real-life cohort.\u0000 \u0000 \u0000 \u0000 All patients initiating JAK inhibitors for active moderate-to-severe CD or UC at our center were included. Patients were prospectively monitored at prespecified timepoints, and specifically assessed for AEs including acne. Affected patients completed a visual analogue scale (VAS) to assess the impact of acne on their quality of life. All pictures of skin lesions were assessed by a dermatologist specialized in inflammatory skin diseases.\u0000 \u0000 \u0000 \u0000 In total, 46 patients initiated TFC, 40 FIL and 79 UPA. None of the TFC or FIL treated patients reported new onset of acne. Instead, 17 (21.5%) patients (9 CD, 8 UC; median [IQR] age 28.2 [25.2-45.0]; 47.1% female) spontaneously reported acne during UPA therapy. Most (89.5%) reported new onset of acne, while 2 (10.5%) mentioned a deterioration of existing acne during UPA induction. Previous acne during adolescence was reported by 46.2%. Lesions were present in the face (82.3%), back (23.5%), chest (23.5%) and scalp (11.8%). The acne phenotype included inflammatory papules in all patients, but also pustules (66.7%), nodules (33.3%), cysts (11.1%) and comedones (11.1%) were observed. A median VAS score of 5.5 [5.0-7.0] highlighted the impact on the patient’s quality of life, though no patient interrupted UPA due to acne. Six (35.2%) patients were referred to a dermatologist for acne. Most patients (82.4%) received topical skin therapy during UPA induction based on a standard operation procedure approved by the dermatologist and communicated via the IBD nurses. Three patients (17.6%) received antibiotics during UPA induction because of acne. During UPA maintenance, 5 patients (29.4%) reported resolution of skin problems with only 1 requiring continued skin therapy. Ten patients (58.7%) continued topical skin therapy during maintenance, with 4 of them requiring continued antibiotic treatment for at least 3 months. A single patient was deescalated from UPA 30mg to 15mg QD because of severe acne, with little improvement.\u0000 \u0000 \u0000 \u0000 In this real-world experience, JAK inhibitor associated acne was uniquely linked to UPA, occurring in one fifth of patients. This is more prevalent than observed in the registrational trials. Awareness and patient education are therefore important, as well as early referral to the dermatologist for appropriate treatment.\u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631636","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 : 2024-01-01DOI: 10.1093/ecco-jcc/jjad212.0596
G. Mulinacci, L. Pirola, D. Gandola, D. Ippolito, C. Viganò, A. Laffusa, C. Gallo, P. Invernizzi, S. Danese, S. Massironi
Sarcopenia is prevalent among patients with Inflammatory Bowel Disease (IBD) and impacts IBD patient’s surgical and therapeutic outcomes, thus necessitating effective diagnostic tools to assess muscle mass and function in this population. A total of 153 consecutive patients were enrolled, 100 in the "training cohort" and 53 in the "study cohort". Three superficial muscles (Rectus Femoris (RF), Rectus Abdominis (RA) and Biceps Brachii (BB)) were chosen for sarcopenia detection with muscle ultrasound (US). The "training cohort" served for feasibility and interobserver variability assessment of US measurement. In the "study cohort", muscle ultrasound (US), bioelectrical impedance analysis (BIA), and magnetic resonance imaging (MRI) were employed to measure muscle parameters. BIA served as the reference standard for comparison. Accuracy of a self-reported questionnaire for sarcopenia screening was assessed. The prevalence of sarcopenia in IBD patients was 50%. Muscle US demonstrated good diagnostic accuracy in detecting sarcopenia compared to BIA, with Area Under the Receiver Operating Characteristic Curve (AUROC) values of 80% and 85% for RA and BB thickness, respectively. Moreover, an Ultrasound Muscle Index (USMI) was defined by the sum of RA, BB, and RF thickness measurements divided by the square of the patient's height, resulting in an AUROC of 81%. Several muscle cutoffs for sarcopenia were recognized, with those of RA and USMI being correlated with the highest positive (84.3%) and negative (99%) predictive values, respectively. Excellent inter-rater and intra-rater reliability (ICC > 0.95) were observed for US measurements. Additionally, the agreement between the US and magnetic resonance measurements of rectus abdominis was excellent (ICC 0.96). The findings of this study emphasize the potential of muscle US as a reliable diagnostic tool for assessing sarcopenia in IBD patients. The study provides cutoff values for US measurements, aiding clinicians in accurate diagnosis. Self-reported questionnaires showed limitations in identifying sarcopenia, underlining the importance of objective measures like US or BIA. Muscle loss in IBD patients appears to be associated with disease activity rather than systemic inflammatory markers. This research has significant implications for disease management in IBD patients and underscores the need for further investigations with larger cohorts and long-term follow-ups to validate these findings.
{"title":"P466 Ultrasound muscle assessment for sarcopenia screening in patients with Inflammatory Bowel Disease: A prospective study (SarcUS-IBD)","authors":"G. Mulinacci, L. Pirola, D. Gandola, D. Ippolito, C. Viganò, A. Laffusa, C. Gallo, P. Invernizzi, S. Danese, S. Massironi","doi":"10.1093/ecco-jcc/jjad212.0596","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0596","url":null,"abstract":"\u0000 \u0000 \u0000 Sarcopenia is prevalent among patients with Inflammatory Bowel Disease (IBD) and impacts IBD patient’s surgical and therapeutic outcomes, thus necessitating effective diagnostic tools to assess muscle mass and function in this population.\u0000 \u0000 \u0000 \u0000 A total of 153 consecutive patients were enrolled, 100 in the \"training cohort\" and 53 in the \"study cohort\". Three superficial muscles (Rectus Femoris (RF), Rectus Abdominis (RA) and Biceps Brachii (BB)) were chosen for sarcopenia detection with muscle ultrasound (US). The \"training cohort\" served for feasibility and interobserver variability assessment of US measurement. In the \"study cohort\", muscle ultrasound (US), bioelectrical impedance analysis (BIA), and magnetic resonance imaging (MRI) were employed to measure muscle parameters. BIA served as the reference standard for comparison. Accuracy of a self-reported questionnaire for sarcopenia screening was assessed.\u0000 \u0000 \u0000 \u0000 The prevalence of sarcopenia in IBD patients was 50%. Muscle US demonstrated good diagnostic accuracy in detecting sarcopenia compared to BIA, with Area Under the Receiver Operating Characteristic Curve (AUROC) values of 80% and 85% for RA and BB thickness, respectively. Moreover, an Ultrasound Muscle Index (USMI) was defined by the sum of RA, BB, and RF thickness measurements divided by the square of the patient's height, resulting in an AUROC of 81%. Several muscle cutoffs for sarcopenia were recognized, with those of RA and USMI being correlated with the highest positive (84.3%) and negative (99%) predictive values, respectively. Excellent inter-rater and intra-rater reliability (ICC > 0.95) were observed for US measurements. Additionally, the agreement between the US and magnetic resonance measurements of rectus abdominis was excellent (ICC 0.96).\u0000 \u0000 \u0000 \u0000 The findings of this study emphasize the potential of muscle US as a reliable diagnostic tool for assessing sarcopenia in IBD patients. The study provides cutoff values for US measurements, aiding clinicians in accurate diagnosis. Self-reported questionnaires showed limitations in identifying sarcopenia, underlining the importance of objective measures like US or BIA. Muscle loss in IBD patients appears to be associated with disease activity rather than systemic inflammatory markers. This research has significant implications for disease management in IBD patients and underscores the need for further investigations with larger cohorts and long-term follow-ups to validate these findings.\u0000 \u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631673","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 : 2024-01-01DOI: 10.1093/ecco-jcc/jjad212.0715
J. H. Bae, J. B. Park, J. Baek, S. W. Hong, S. Park, D. H. Yang, B. Ye, J. Byeon, S. Myung, S. K. Yang, S. Hwang
Studies on elective switching to the subcutaneous (SC) formulation of infliximab revealed comparable efficacy and safety and higher infliximab level than those exhibited by intravenous (IV) infliximab. However, no studies have reported on the effectiveness of SC switching in ulcerative colitis (UC) patients who experienced IV infliximab failure during maintenance treatment. This retrospective study included UC patients who had been switched to SC infliximab because of IV infliximab failure, between January 2021 and January 2023. Group A was defined as having clinically and biochemically active UC (secondary loss of response), and group B consisted of patients with stable symptoms but biochemically active UC. Twenty-three patients met the inclusion criteria: 15 in group A and 8 in group B. The serum infliximab levels significantly increased after SC switching in both groups. Electively switched group also exhibited increased infliximab levels after SC switching. Group A showed improved partial Mayo score with a significant decrease in faecal calprotectin (FC) and C-reactive protein after switching. In group B, the FC level significantly decreased without clinical relapse after switching. A high proportion of patients (≥ 80%) in both groups achieved clinical and/or biochemical response at last follow-up. During the follow-up period, only two patients in group A discontinued SC infliximab, and only one complained of severe injection site reaction. In UC patients who experience IV infliximab failure during maintenance treatment, switching to SC infliximab may be a promising option because of its efficacy and safety.
关于选择改用英夫利西单抗皮下注射制剂的研究显示，与静脉注射英夫利西单抗相比，皮下注射英夫利西单抗的疗效和安全性相当，英夫利西单抗水平也更高。然而，对于在维持治疗期间静脉注射英夫利西单抗失败的溃疡性结肠炎（UC）患者，还没有关于皮下注射英夫利西单抗的有效性的研究报告。 这项回顾性研究纳入了 2021 年 1 月至 2023 年 1 月期间因静脉注射英夫利西单抗失败而改用静脉注射英夫利西单抗的 UC 患者。A组定义为临床和生化活动性UC（继发性应答丧失），B组包括症状稳定但生化活动性UC患者。 23 名患者符合纳入标准：两组患者的血清英夫利西单抗水平在SC转换后均显著升高。选择性换药组在换药后也显示出英夫利西单抗水平的升高。A 组的部分梅奥评分有所改善，换药后粪便钙粘蛋白（FC）和 C 反应蛋白明显下降。在 B 组中，换药后 FC 水平明显下降，但无临床复发。在最后一次随访中，两组中均有很高比例的患者（≥ 80%）获得了临床和/或生化应答。在随访期间，A 组仅有两名患者停用了 SC 英夫利西单抗，仅有一名患者抱怨出现了严重的注射部位反应。 对于在维持治疗过程中静脉注射英夫利西单抗失败的 UC 患者，改用 SC 英夫利西单抗可能是一个很有前途的选择，因为它既有效又安全。
{"title":"P585 Effectiveness of Switching to Subcutaneous Infliximab in Ulcerative Colitis Patients Experiencing Intravenous Infliximab Failure","authors":"J. H. Bae, J. B. Park, J. Baek, S. W. Hong, S. Park, D. H. Yang, B. Ye, J. Byeon, S. Myung, S. K. Yang, S. Hwang","doi":"10.1093/ecco-jcc/jjad212.0715","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjad212.0715","url":null,"abstract":"\u0000 \u0000 \u0000 Studies on elective switching to the subcutaneous (SC) formulation of infliximab revealed comparable efficacy and safety and higher infliximab level than those exhibited by intravenous (IV) infliximab. However, no studies have reported on the effectiveness of SC switching in ulcerative colitis (UC) patients who experienced IV infliximab failure during maintenance treatment.\u0000 \u0000 \u0000 \u0000 This retrospective study included UC patients who had been switched to SC infliximab because of IV infliximab failure, between January 2021 and January 2023. Group A was defined as having clinically and biochemically active UC (secondary loss of response), and group B consisted of patients with stable symptoms but biochemically active UC.\u0000 \u0000 \u0000 \u0000 Twenty-three patients met the inclusion criteria: 15 in group A and 8 in group B. The serum infliximab levels significantly increased after SC switching in both groups. Electively switched group also exhibited increased infliximab levels after SC switching. Group A showed improved partial Mayo score with a significant decrease in faecal calprotectin (FC) and C-reactive protein after switching. In group B, the FC level significantly decreased without clinical relapse after switching. A high proportion of patients (≥ 80%) in both groups achieved clinical and/or biochemical response at last follow-up. During the follow-up period, only two patients in group A discontinued SC infliximab, and only one complained of severe injection site reaction.\u0000 \u0000 \u0000 \u0000 In UC patients who experience IV infliximab failure during maintenance treatment, switching to SC infliximab may be a promising option because of its efficacy and safety.\u0000 \u0000 \u0000","PeriodicalId":15453,"journal":{"name":"Journal of Crohn's and Colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631898","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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