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Effects of COVID-19 vaccines on patient-reported outcomes in patients with inflammatory bowel disease: a multicenter survey study in Korea. COVID-19 疫苗对炎症性肠病患者报告结果的影响:韩国多中心调查研究。
IF 3.4 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-07-01 Epub Date: 2024-03-26 DOI: 10.5217/ir.2023.00077
Jung Hyun Ji, Seung Hwan Shin, Yong Eun Park, Jihye Park, Jae Jun Park, Jae Hee Cheon, Tae Il Kim, Sang-Bum Kang, Sang Hyoung Park, Soo Jung Park

Background/aims: The impact of vaccination on inflammatory bowel disease (IBD) patients is still unknown, and no studies have assessed the changes in patient-reported outcomes (PROs) after vaccination in patients with IBD. Therefore, in this study, we investigated the impact of vaccines on the PROs of patients with IBD.

Methods: We conducted a questionnaire survey of patients with IBD who visited outpatient clinics at 4 specialized IBD clinics of referral university hospitals from April 2022 to June 2022. A total of 309 IBD patients were included in the study. Patient information was collected from a questionnaire and their medical records, including laboratory findings, were reviewed retrospectively. Risk factors associated with an increase in PROs after COVID-19 vaccination were analyzed using logistic regression analyses. In addition, we assessed whether there were differences in variables by vaccine order using the linear mixed model.

Results: In multivariate analysis, young age ( < 40 years) and ulcerative colitis (UC) were found to be independent risk factors for aggravation of PROs in patients with IBD. In all patients, platelet count significantly increased with continued vaccination in multiple pairwise comparisons. In UC patients, PROs such as the short health scale, UC-abdominal signs and symptoms, and UC-bowel signs and symptoms were aggravated significantly with continued vaccination. There was no significant increase in the variables of patients with Crohn's disease.

Conclusions: Therefore, there may be a need to counsel patients with IBD younger than 40 years of age, and patients with UC before they receive COVID-19 vaccinations.

背景/目的:疫苗接种对炎症性肠病(IBD)患者的影响尚不清楚,也没有研究评估了IBD患者接种疫苗后患者报告结果(PROs)的变化。因此,在本研究中,我们调查了疫苗对 IBD 患者的 PROs 的影响:方法:我们对 2022 年 4 月至 2022 年 6 月期间在 4 家转诊大学医院 IBD 专科门诊就诊的 IBD 患者进行了问卷调查。共有 309 名 IBD 患者被纳入研究。研究人员通过问卷收集了患者信息,并回顾性审查了他们的病历,包括实验室检查结果。我们使用逻辑回归分析法对接种 COVID-19 疫苗后 PROs 增加的相关风险因素进行了分析。此外,我们还使用线性混合模型评估了不同疫苗接种顺序的变量是否存在差异:结果:在多变量分析中发现,年轻(< 40 岁)和溃疡性结肠炎(UC)是导致 IBD 患者 PROs 恶化的独立风险因素。在多对比较中,所有患者的血小板计数都随着持续接种疫苗而明显增加。在 UC 患者中,简易健康量表、UC 腹部体征和症状以及 UC 肠道体征和症状等 PROs 在持续接种疫苗后明显加重。克罗恩病患者的变量没有明显增加:因此,40 岁以下的 IBD 患者和 UC 患者在接种 COVID-19 疫苗前可能需要进行咨询。
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引用次数: 0
Changes in the clinical course and prognosis of ulcerative colitis in Chinese populations: a retrospective cohort study. 中国人群溃疡性结肠炎临床过程和预后的变化:一项回顾性队列研究。
IF 3.4 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-07 DOI: 10.5217/ir.2023.00106
Xinyu Liu, Qingfan Yang, Na Diao, Jian Tang, Zicheng Huang, Xiang Gao, Kang Chao

Background/aims: Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China.

Methods: This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007-2011, cohort II: 2012-2016, cohort III: 2017-2021). Patients' clinical characteristics and natural history were analyzed retrospectively.

Results: Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P= 0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P< 0.001), so did the use of glucocorticoids (58.2% vs. 43.5%, P< 0.001) and immunosuppressants (14.1% vs. 13.4%, P= 0.016), and days of hospitalization (13 days vs. 9 days, P< 0.001). Biologics were used more frequently during the first year (0.8%, 2.1%, and 13.7% for cohorts I to III, respectively; P< 0.001). The rate of mucosal healing increased over time.

Conclusions: In Chinese UC patients, one-third of patients experienced proximal disease extension. The rates of malignancy and mortality were low. More biologics were used, while use of immunosuppressants and glucocorticoids were reduced over time. Early biologics use seemed to promote mucosal healing, but the rate of colectomy has not dramatically decreased.

背景/目的:有关中国溃疡性结肠炎(UC)患者自然病程的数据十分缺乏。本研究旨在评估过去15年中国溃疡性结肠炎患者的自然病史和预后:这项队列研究纳入了2007年至2021年在中国南方一家三甲医院就诊的UC患者(队列I:2007-2011年;队列II:2012-2016年;队列III:2017-2021年)。对患者的临床特征和自然病史进行回顾性分析:在纳入的1139名患者中,683名患者在确诊时表现为直肠炎或左侧结肠炎,其中38.5%的患者(263/683)出现了近端疾病扩展。58%的患者经历了复发、慢性持续性和间歇性活动期。5名患者(0.4%)出现结直肠肿瘤/增生。总手术率为8.6%,三组患者的手术率分别为14.2%、7.8%和8.0%(P= 0.059)。从诊断到手术的平均时间从第一组到第三组有所缩短(144 个月对 36 个月,P< 0.001),糖皮质激素(58.2% 对 43.5%,P< 0.001)和免疫抑制剂(14.1% 对 13.4%,P= 0.016)的使用率以及住院天数也有所缩短(13 天对 9 天,P< 0.001)。生物制剂在第一年的使用频率更高(第一组至第三组分别为 0.8%、2.1% 和 13.7%;P< 0.001)。随着时间的推移,粘膜愈合率也在增加:结论:在中国的 UC 患者中,三分之一的患者出现了近端疾病扩展。结论:在中国的 UC 患者中,三分之一的患者出现了近端疾病扩展,恶性肿瘤发生率和死亡率较低。随着时间的推移,免疫抑制剂和糖皮质激素的使用逐渐减少。早期生物制剂的使用似乎促进了粘膜愈合,但结肠切除术的比例并未显著下降。
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引用次数: 0
Halitosis: an underestimated but important extraintestinal manifestation in inflammatory bowel disease. 口臭:炎症性肠病中被低估但重要的肠外表现。
IF 3.4 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-07 DOI: 10.5217/ir.2024.00016
Xiao Xian Qian
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引用次数: 0
Long-term efficacy and safety of tofacitinib in patients with ulcerative colitis: 3-year results from a real-world study. 托法替尼对溃疡性结肠炎患者的长期疗效和安全性:一项真实世界研究的三年结果。
IF 3.4 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-07-01 Epub Date: 2024-07-16 DOI: 10.5217/ir.2023.00194
Hiromichi Shimizu, Yuko Aonuma, Shuji Hibiya, Ami Kawamoto, Kento Takenaka, Toshimitsu Fujii, Eiko Saito, Masakazu Nagahori, Kazuo Ohtsuka, Ryuichi Okamoto

Background/aims: The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles.

Methods: A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events.

Results: Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study.

Conclusions: Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice.

背景/目的:托法替尼治疗难治性溃疡性结肠炎(UC)的有效性和安全性已在临床试验中得到证实。尽管已经发表了一系列有关其短期疗效和安全性的真实世界证据报告,但有关长期真实世界数据的报告却很有限。我们旨在展示临床使用托法替尼治疗 UC 的 3 年证据,重点关注其疗效和安全性:我们对本院开始使用托法替尼治疗活动性难治性 UC 的患者进行了一项回顾性观察研究。主要结果是患者在开始服用托法替尼 156 周后的保留率。次要结果为4周、8周和12周的短期疗效;52周、104周和156周的长期疗效;与累计保留率相关的预后因素;应答丧失;以及包括不良事件在内的安全性概况:46名患者在开始服用托法替尼后接受了长达156周的监测。54.3%的患者可继续服用托法替尼至156周,其中应答率>50%,缓解率>40%。在诱导治疗8周后获得应答或缓解并停用托法替尼的患者中,有54.3%的患者复发,但除1名患者外,其余患者均被成功挽救并继续接受诱导治疗。研究中未观察到严重的不良反应:在实际临床实践中,托法替尼对难治性UC患者群的长期治疗有效且安全。
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引用次数: 0
Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023. 台湾溃疡性结肠炎的管理:台湾炎症性肠病学会共识指南(2023 年更新)》。
IF 3.4 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-07-01 Epub Date: 2024-07-29 DOI: 10.5217/ir.2023.00050
Hsu-Heng Yen, Jia-Feng Wu, Horng-Yuan Wang, Ting-An Chang, Chung-Hsin Chang, Chen-Wang Chang, Te-Hsin Chao, Jen-Wei Chou, Yenn-Hwei Chou, Chiao-Hsiung Chuang, Wen-Hung Hsu, Tzu-Chi Hsu, Tien-Yu Huang, Tsung-I Hung, Puo-Hsien Le, Chun-Che Lin, Chun-Chi Lin, Ching-Pin Lin, Jen-Kou Lin, Wei-Chen Lin, Yen-Hsuan Ni, Ming-Jium Shieh, I-Lun Shih, Chia-Tung Shun, Tzung-Jiun Tsai, Cheng-Yi Wang, Meng-Tzu Weng, Jau-Min Wong, Deng-Chyang Wu, Shu-Chen Wei

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

溃疡性结肠炎(UC)是一种慢性胃肠道炎症,其特点是炎症和缓解期交替出现。虽然台湾的溃疡性结肠炎发病率低于西方国家,但其影响仍然相当大,因此需要更新指南,以应对当地的医疗挑战和患者需求。修订后的指南采用国际标准和最新研究成果,强调在台湾医疗保健系统中的实际应用。自2017年指南制定以来,台湾炎症性肠病学会一直认为有必要不断修订指南,以纳入新的治疗方案和不断发展的疾病管理实践。本更新指南旨在使 UC 管理与当地情况相一致,确保提供全面且针对具体情况的建议,从而提高台湾 UC 患者的护理标准。通过调整和优化与本地相关的国际方案,这些努力旨在提高 UC 患者的健康状况。
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引用次数: 0
Ustekinumab for anti-tumor necrosis factor refractory pediatric ulcerative colitis: a promising approach towards endoscopic healing. 乌司他单抗治疗抗肿瘤坏死因子难治性小儿溃疡性结肠炎:实现内镜下愈合的前景广阔的方法。
IF 3.4 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-07-01 Epub Date: 2024-02-06 DOI: 10.5217/ir.2023.00091
Rahiya Rehman, Muhammad Safwan Riaz, Dyadin Esharif, Phinnara Has, Michael Herzlinger, Jason Shapiro, Shova Subedi

Background/aims: To describe the role of ustekinumab in inducing remission and endoscopic healing in anti-tumor necrosis factor α nonresponsive pediatric ulcerative colitis patients at a tertiary care inflammatory bowel disease center.

Methods: A retrospective chart review was performed on patients with ulcerative colitis receiving ustekinumab. Primary outcome was steroidfree clinical remission at follow-up. Secondary outcomes were biochemical remission and endoscopic healing.

Results: Ten children were analyzed; 7 (70%) had ulcerative colitis, and 3 (30%) had inflammatory bowel disease unspecified with colitis. Median follow-up period was 56 weeks. Nine patients (90%) achieved steroid-free clinical remission and biochemical remission. Seven patients had follow-up colonoscopies, out of which 6 (86%) achieved endoscopic remission, while 1 (14%) underwent colectomy. Out of the 3 patients without a follow-up colonoscopy, fecal calprotectin levels downtrended to < 150 mg/kg in 2 patients and < 400 mg/kg in 1 patient from baseline level of > 2,000 mg/kg.

Conclusions: Ustekinumab appears efficacious in achieving not only clinical and biochemical remission but also has promising role in inducing endoscopic healing end point in patients who fail other biologics.

背景/目的描述乌司替库单抗在一家三级医疗炎症性肠病中心诱导抗肿瘤坏死因子α无反应的小儿溃疡性结肠炎患者病情缓解和内镜愈合中的作用:对接受乌司替尼治疗的溃疡性结肠炎患者进行回顾性病历审查。主要结果是随访期间无类固醇临床缓解。次要结果是生化缓解和内镜愈合:结果:10名儿童接受了分析,其中7名(70%)患有溃疡性结肠炎,3名(30%)患有不明原因的炎症性肠病合并结肠炎。中位随访期为 56 周。九名患者(90%)实现了无类固醇临床缓解和生化缓解。7 名患者接受了结肠镜随访,其中 6 人(86%)获得了内镜下缓解,1 人(14%)接受了结肠切除术。在没有进行后续结肠镜检查的3名患者中,有2名患者的粪钙蛋白水平从基线水平> 2,000毫克/千克降至< 150毫克/千克,1名患者降至< 400毫克/千克:乌司替库单抗不仅能有效实现临床和生化缓解,还能在诱导其他生物制剂治疗失败的患者达到内镜下愈合终点方面发挥重要作用。
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引用次数: 0
Diagnostic strategy of irritable bowel syndrome: a low- and middle-income country perspective. 肠易激综合征的诊断策略:中低收入国家的视角。
IF 3.4 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-07-01 Epub Date: 2024-03-26 DOI: 10.5217/ir.2023.00199
Amal Arifi Hidayat, Langgeng Agung Waskito, Titong Sugihartono, Hafeza Aftab, Yudith Annisa Ayu Rezkitha, Ratha-Korn Vilaichone, Muhammad Miftahussurur

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder associated with substantial impairment which considerably burdens healthcare systems worldwide. Research on IBS has largely been conducted in high-income countries posing barriers to the application of diagnostic strategies in low- and middle-income countries (LMICs) due to differences in disease characteristics, healthcare resources, and socioeconomic factors. This review discusses the diagnostic issues associated with LMICs. We present a concise overview of the relevant approaches and propose a diagnostic strategy based on the latest evidence. A positive diagnostic strategy that relies on appropriate symptom-based criteria is crucial within the diagnostic framework. A combination of complete blood count, fecal occult blood test, and complete stool test may reliably identify individuals with suspected IBS who are more likely to have organic diseases, thus justifying the necessity for a colonoscopy. Eventually, we developed a diagnostic algorithm based on a limited setting perspective that summarizes the available evidence and may be applied in LMICs.

肠易激综合征(IBS)是一种发病率很高的胃肠道疾病,会对人体造成严重损害,给全世界的医疗保健系统带来沉重负担。由于疾病特征、医疗资源和社会经济因素的差异,有关肠易激综合征的研究大多在高收入国家进行,这给在中低收入国家(LMIC)应用诊断策略造成了障碍。本综述讨论了与中低收入国家相关的诊断问题。我们简要概述了相关方法,并根据最新证据提出了诊断策略。在诊断框架内,基于适当症状标准的积极诊断策略至关重要。结合全血细胞计数、粪便潜血试验和大便常规试验,可以可靠地识别出更有可能患有器质性疾病的疑似肠易激综合征患者,从而证明结肠镜检查的必要性。最后,我们从有限环境的角度出发,总结了现有的证据,制定了一套诊断算法,可用于低收入国家。
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引用次数: 0
Adequacy of sigmoidoscopy as compared to colonoscopy for assessment of disease activity in patients of ulcerative colitis: a prospective study. 在评估溃疡性结肠炎患者的疾病活动性时,乙状结肠镜检查与结肠镜检查相比是否足够:一项前瞻性研究。
IF 3.4 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-16 DOI: 10.5217/ir.2023.00174
Sameet Tariq Patel, Anuraag Jena, Sanjay Chandnani, Shubham Jain, Pankaj Nawghare, Saurabh Bansal, Harsh Gandhi, Rishikesh Malokar, Jay Chudasama, Prasanta Debnath, Seemily Kahmei, Rima Kamat, Sangeeta Kini, Qais Q Contractor, Pravin M Rathi

Background/aims: Patients of ulcerative colitis (UC) on follow-up are routinely evaluated by sigmoidoscopy. There is no prospective literature to support this practice. We assessed agreement between sigmoidoscopy and colonoscopy prospectively in patients with disease extent beyond the sigmoid colon.

Methods: We conducted a prospective observational study at a tertiary care institute for agreement between sigmoidoscopy and colonoscopy. We assessed endoscopic activity using the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and histological activity using the Nancy Index (NI), Robarts Histopathology Index (RHI), and Simplified Geboes Score (SGS).

Results: Sigmoidoscopy showed a strong agreement with colonoscopy for MES and UCEIS with a kappa (κ) of 0.96 and 0.94 respectively. The misclassification rate for MES and UCEIS was 3% and 5% respectively. Sigmoidoscopy showed perfect agreement (κ = 1.00) with colonoscopy for assessment of the presence of endoscopic activity in the colon using MES ≥ 1 as activity criteria and strong agreement (κ = 0.93) using MES > 1 as activity criteria. Sigmoidoscopy showed strong agreement with colonoscopy for assessment of the presence of endoscopic activity using UCEIS (κ = 0.92). Strong agreement was observed between sigmoidoscopy and colonoscopy using NI (κ = 0.86), RHI (κ = 1.00), and SGS (κ = 0.92) for the detection of histological activity. The misclassification rate for the detection of histological activity was 2%, 0%, and 1% for NI, RHI, and SGS respectively.

Conclusions: Sigmoidoscopy showed strong agreement with colonoscopy for endoscopic and histologic disease activity. Sigmoidoscopy is adequate for assessment of disease activity in patients with UC during follow-up evaluation.

背景/目的:对溃疡性结肠炎(UC)患者进行随访时,通常都要进行乙状结肠镜检查。目前还没有前瞻性文献支持这种做法。我们对疾病范围超过乙状结肠的患者进行了乙状结肠镜检查和结肠镜检查的一致性前瞻性评估:我们在一家三级医疗机构开展了一项前瞻性观察研究,以评估乙状结肠镜检查和结肠镜检查之间的一致性。我们使用梅奥内镜评分(MES)和溃疡性结肠炎内镜严重程度指数(UCEIS)评估内镜活动度,使用南希指数(NI)、罗巴特组织病理学指数(RHI)和简化吉布斯评分(SGS)评估组织学活动度:乙状结肠镜检查与结肠镜检查在 MES 和 UCEIS 方面显示出很高的一致性,卡帕(K)分别为 0.96 和 0.94。MES和UCEIS的误诊率分别为3%和5%。乙状结肠镜检查与结肠镜检查在以 MES ?1 为活动标准评估结肠是否存在内镜活动方面显示出完美的一致性(K = 1.00),而以 MES > 1 为活动标准则显示出很强的一致性(K = 0.93)。乙状结肠镜与结肠镜在使用 UCEIS 评估是否存在内镜活动方面显示出很高的一致性(K = 0.92)。使用 NI(K = 0.86)、RHI(K = 1.00)和 SGS(K = 0.92)检测组织学活动性时,乙状结肠镜检查和结肠镜检查之间的一致性很高。NI、RHI和SGS检测组织学活动的误判率分别为2%、0%和1%:结论:乙状结肠镜检查与结肠镜检查在内镜和组织学疾病活动性方面显示出很强的一致性。乙状结肠镜检查足以在随访评估期间评估 UC 患者的疾病活动性。
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引用次数: 0
Efficacy and safety of mirikizumab as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a subgroup analysis of the global phase 3 LUCENT-1 and LUCENT-2 studies. 米利珠单抗作为日本中度至重度活动性溃疡性结肠炎患者的诱导和维持疗法的疗效和安全性:全球三期 LUCENT-1 和 LUCENT-2 研究的亚组分析。
IF 4.9 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-04-01 Epub Date: 2024-04-25 DOI: 10.5217/ir.2023.00043
Taku Kobayashi, Katsuyoshi Matsuoka, Mamoru Watanabe, Tadakazu Hisamatsu, Fumihito Hirai, Joe Milata, Xingyuan Li, Nathan Morris, Vipin Arora, Tomoko Ishizuka, Koji Matsuo, Yoichi Satoi, Catherine Milch, Toshifumi Hibi

Background/aims: Mirikizumab is a p19-directed anti-interleukin-23 antibody with potential efficacy against ulcerative colitis (UC). We evaluated the efficacy and safety of mirikizumab in a Japanese subpopulation with moderately to severely active UC from the LUCENT-1 and LUCENT-2 studies.

Methods: LUCENT-1 and LUCENT-2 were phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab therapy in adults with moderately to severely active UC. LUCENT-1 was a 12-week induction trial where patients were randomized 3:1 to receive intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W). Patients achieving a clinical response with mirikizumab following the induction study were re-randomized 2:1 to double-blind treatment with either mirikizumab 200 mg or placebo subcutaneously Q4W during the 40-week maintenance study. The primary outcomes were clinical remission at week 12 of LUCENT-1 and week 40 of LUCENT-2.

Results: A total of 137 patients enrolled in Japan were randomized to mirikizumab (n = 102) or placebo (n = 35). Compared with placebo, patients who received mirikizumab showed numerically higher clinical remission at week 12 of induction (32.4% [n = 33] vs. 2.9% [n = 1]) and at week 40 of maintenance (48.9% [n = 23] vs. 28.0% [n = 7]). A greater number of patients achieved key secondary endpoints in the mirikizumab group compared with placebo. The frequency of treatment-emergent adverse events was similar across mirikizumab and placebo groups. Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population.

Conclusions: Mirikizumab induction and maintenance treatments were effective in Japanese patients with moderately to severely active UC. No new safety concerns were identified.

背景/目的:米利珠单抗是一种p19导向的抗白细胞介素-23抗体,对溃疡性结肠炎(UC)具有潜在疗效。我们从 LUCENT-1 和 LUCENT-2 研究中评估了米利珠单抗在中度至重度活动性 UC 日本亚群中的疗效和安全性:LUCENT-1和LUCENT-2是米利珠单抗治疗中重度活动性UC成人患者的3期随机、双盲、安慰剂对照试验。LUCENT-1是一项为期12周的诱导试验,患者按3:1的比例随机分配,每4周(Q4W)接受一次静脉注射300毫克米利珠单抗或安慰剂。诱导研究结束后,使用米利珠单抗获得临床应答的患者将以2:1的比例重新随机分配到双盲治疗中,在为期40周的维持治疗研究中,每4周皮下注射米利珠单抗200毫克或安慰剂。主要结果为LUCENT-1第12周和LUCENT-2第40周的临床缓解:日本共有137名患者随机接受了米利珠单抗(102人)或安慰剂(35人)治疗。与安慰剂相比,接受米利珠单抗治疗的患者在诱导治疗第12周(32.4% [n = 33] vs. 2.9% [n = 1])和维持治疗第40周(48.9% [n = 23] vs. 28.0% [n = 7])的临床缓解率均高于安慰剂。与安慰剂组相比,米利珠单抗组达到关键次要终点的患者人数更多。米利珠单抗组和安慰剂组发生治疗突发不良事件的频率相似。在日本亚人群中观察到的疗效和安全性结果与总体人群的结果基本一致:结论:米利珠单抗诱导和维持治疗对中度至重度活动性 UC 日本患者有效。没有发现新的安全性问题。
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引用次数: 0
Unraveling molecular similarities between colorectal polyps and colorectal cancer: a systems biology approach. 揭示大肠息肉与大肠癌之间的分子相似性:一种系统生物学方法。
IF 4.9 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-04-01 Epub Date: 2024-02-06 DOI: 10.5217/ir.2023.00162
Mehran Radak, Hossein Fallahi

Background/aims: Colorectal cancer (CRC) and colorectal polyps are intimately linked, with polyps acting as precursors to CRC. Understanding the molecular mechanisms governing their development is crucial for advancing diagnosis and treatment. Employing a systems biology approach, we investigated the molecular similarities between polyp and CRC.

Methods: We analyzed gene expression profiles, protein-protein interactions, transcription factors, and gene ontology to identify common differentially expressed genes (DEGs) and unravel shared molecular pathways.

Results: Our analysis revealed 520 commonly dysregulated genes in polyps and CRC, serving as potential biomarkers and pivotal contributors to disease progression. Gene ontology analysis elucidated distinct biological processes associated with upregulated and downregulated DEGs in both conditions, highlighting common pathways, including signal transduction, cell adhesion, and positive regulation of cell proliferation. Moreover, protein-protein interaction networks shed light on subnetworks involved in rRNA processing, positive regulation of cell proliferation, mRNA splicing, and cell division. Transcription factor analysis identified major regulators and differentially expressed transcription factors in polyp and CRC. Notably, we identified common differentially expressed transcription factors, including ZNF217, NR3C1, KLF5, GATA6, and STAT3, with STAT3 and NR3C1 exhibiting increased expression.

Conclusions: This comprehensive analysis enriches our understanding of the molecular mechanisms underlying polyp formation and CRC development, providing potential targets for further investigation and therapeutic intervention. Our findings contribute substantively to crafting personalized strategies for refining the diagnosis and treatment of polyps and CRC.

背景/目的:结肠直肠癌(CRC)与结肠直肠息肉密切相关,息肉是 CRC 的前体。了解制约其发展的分子机制对于促进诊断和治疗至关重要。我们采用系统生物学方法研究了息肉和 CRC 之间的分子相似性:方法:我们分析了基因表达谱、蛋白-蛋白相互作用、转录因子和基因本体,以确定常见的差异表达基因(DEGs),并揭示共同的分子通路:结果:我们的分析揭示了息肉和 CRC 中 520 个常见的失调基因,这些基因是潜在的生物标记物,也是疾病进展的关键因素。基因本体分析阐明了两种疾病中与上调和下调DEGs相关的不同生物过程,突出了共同的通路,包括信号转导、细胞粘附和细胞增殖的正向调节。此外,蛋白质-蛋白质相互作用网络还揭示了参与 rRNA 处理、细胞增殖正向调控、mRNA 剪接和细胞分裂的子网络。转录因子分析确定了息肉和 CRC 中的主要调控因子和差异表达的转录因子。值得注意的是,我们发现了常见的差异表达转录因子,包括 ZNF217、NR3C1、KLF5、GATA6 和 STAT3,其中 STAT3 和 NR3C1 的表达量有所增加:这项综合分析丰富了我们对息肉形成和 CRC 发展的分子机制的认识,为进一步研究和治疗干预提供了潜在靶点。我们的研究结果有助于制定个性化策略,完善息肉和 CRC 的诊断和治疗。
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Intestinal Research
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