|
1
|
Ohmori T. Real-World Effectiveness and Safety of Carotegrast Methyl in Japanese Patients with Moderately Active Ulcerative Colitis. Inflamm Intest Dis 2024; 9:271-282. [PMID: 39563683 PMCID: PMC11575925 DOI: 10.1159/000541663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Accepted: 09/25/2024] [Indexed: 11/21/2024] Open
Abstract
Introduction Carotegrast methyl (CGM) is an oral, small-molecule α4-integrin antagonist, which became clinically available in Japan in May 2022. CGM is approved for remission induction treatment for moderately active ulcerative colitis (UC) with an inadequate response or intolerance to 5-aminosalicylates. Methods We performed a single-center, retrospective, observational study of Japanese patients with moderately active UC to assess the real-world effectiveness and safety of CGM as remission induction treatment. Results Of 14 patients, 71% (10/14) were women, and the median (range) age was 47 (20-68) years. Disease types were proctitis in 7% (1/14), left-sided colitis in 50% (7/14), and total colitis in 43% (6/14). With a median (range) treatment duration of 8 (2-26) weeks, the rate of endoscopic improvement (Mayo endoscopic subscore [MES] of 0 or 1) was 64% (9/14), and the rate of endoscopic remission (MES of 0) was 57% (8/14). After treatment with CGM, the median (range) MES decreased significantly from 3.0 (2-3) to 0.0 (0-3) (p = 0.008), the Mayo score decreased significantly from 7.0 (5-9) to 0.0 (0-9) (p = 0.006), and the clinical activity index decreased significantly from 6.0 (1-11) to 0.0 (0-9) (p = 0.015). Stool and diarrhea frequencies decreased significantly after initiating CGM, and the percentage of patients with bloody stool and abdominal pain tended to decrease. The cumulative relapse-free rate at week 26 among 9 patients who achieved endoscopic improvement with CGM was 77.8% (95% confidence interval, 36.5%-93.9%). No adverse drug reactions, including progressive multifocal leukoencephalopathy, were reported during the study period. Conclusion This single-center, retrospective, observational study of 14 Japanese patients with UC showed that CGM was safe and effective as a remission induction treatment for moderately active UC with an inadequate response to 5-aminosalicylates in real-world settings.
Collapse
Affiliation(s)
- Toshihide Ohmori
- Department of Gastroenterology, Ohmori Toshihide Gastro-intestinal Clinic, Ageo, Saitama, Japan
| |
Collapse
|
|
2
|
Seong G, Song JH, Kim JE, Kim TJ, Kim ER, Hong SN, Chang DK, Kim SH, Ha SY, Kim YH. Histologic Activity and Steroid Use History Are Risk Factors of Clinical Relapse in Ulcerative Colitis With Mayo Endoscopic Subscore of 0 or 1. Inflamm Bowel Dis 2023; 29:238-244. [PMID: 35396998 DOI: 10.1093/ibd/izac075] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND The treatment goal of ulcerative colitis (UC) has changed from the control of symptoms to mucosal healing, previously evaluated mainly by endoscopy. Recently, the importance of histologic activity has emerged. Therefore, this study aimed to investigate the risk of clinical relapse according to histologic activity in UC with a Mayo endoscopic subsccore (MES) of 0 or 1. METHODS In a retrospective cohort after our center's biopsy guideline for UC was instituted, 492 UC patients with an MES of 0 or 1 were enrolled and analyzed. The primary outcome was the development of a clinical relapse including changes in medication, hospitalization, colectomy, and the development of colorectal cancer during the follow-up period. RESULTS During the median 549 days of follow-up, 92 (18.7%) patients had a clinical relapse. All the patients changed their medication, including 4 hospitalized patients. Histologic activity defined by a Geboes score of ≧3.1 (hazard ratio [HR], 1.732; P = .035) and steroid use history (HR, 1.762; P = .008) were independent factors associated with clinical relapse. When stratified, the 1- and 2-year incidence rates of clinical relapse were 4.1% and 10.6%, respectively, for patients with histologic improvement and no steroid use history, whereas the rates were 23.9% and 39.4% for patients with histologic activity and steroid use history. CONCLUSIONS In UC with an MES of 0 or 1, histologic activity and steroid use history can be used to stratify the risk of clinical relapse.
Collapse
Affiliation(s)
- Gyeol Seong
- Department of Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, Korea
| | - Joo Hye Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Eun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae Jun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun Ran Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Kyung Chang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seok-Hyung Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang Yun Ha
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-Ho Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
3
|
Hunter T, Naegeli AN, Nguyen C, Shan M, Smith JL, Tan H, Gottlieb K, Isenberg K. Medication use among patients with Crohn’s disease or ulcerative colitis before and after the initiation of advanced therapy. BMC Gastroenterol 2022; 22:474. [DOI: 10.1186/s12876-022-02584-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 11/15/2022] [Indexed: 11/21/2022] Open
Abstract
Abstract
Background
Although various treatments help reduce abdominal pain, real-world pain medication utilization among patients with Crohn’s disease (CD) or ulcerative colitis (UC) receiving advanced therapies is poorly understood. The aim is to understand the utilization of pain medication 12 months before and after the initiation of advanced therapies among patients with newly diagnosed CD or UC.
Methods
This retrospective, observational cohort study used administrative medical and pharmacy claims data of patients with CD or UC from HealthCore Integrated Research Database (HIRD®). The data from patients with use of pain medication over 12 months follow-up (after the initiation date of advanced therapies) were collected and analyzed. Differences in the use of pain medication 12 months before and after the initiation of advanced therapies were assessed using McNemar's and Wilcoxon signed-rank test.
Results
Prior to initiating advanced therapies, 23.1% of patients with CD (N = 540) received nonsteroidal anti-inflammatory drugs (NSAIDs), 78.1% glucocorticoids, 49.4% opioids, and 29.3% neuromodulators; similarly, 20.9% of patients with UC (N = 373) received NSAIDs, 91.4% glucocorticoids, 40.8% opioids, and 29.5% neuromodulators. After receiving advanced therapies for 12 months, patients reported a reduction in the use of steroids (78.1% vs. 58.9%, P < 0.001 in CD; 91.4% vs. 74.3%, P < 0.001 in UC), opioids (49.4% vs. 41.5%, P = 0.004 in CD; 40.8% vs. 36.5%, P = 0.194 in UC), and NSAIDs (23.1% vs. 15.0%, P < 0.001 in CD; 20.9% vs. 15.8%, P = 0.035 in UC), while the use of neuromodulators significantly increased (29.3% vs. 33.7%, P = 0.007 in CD; 29.5% vs. 35.7%; P = 0.006 in UC).
Conclusions
The use of pain medications such as NSAIDs, glucocorticoids, opioids, and neuromodulators was common among patients with CD or UC. These results highlight that patients with CD or UC continued to receive pain medications even after initiating advanced therapies.
Collapse
|
|
4
|
Kim JS, Geum MJ, Son ES, Yu YM, Cheon JH, Kwon KH. Improvement in Medication Adherence after Pharmacist Intervention Is Associated with Favorable Clinical Outcomes in Patients with Ulcerative Colitis. Gut Liver 2022; 16:736-745. [PMID: 35145044 PMCID: PMC9474485 DOI: 10.5009/gnl210371] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 10/23/2021] [Accepted: 11/03/2021] [Indexed: 11/18/2022] Open
Abstract
Background/Aims Although pharmacist intervention for patients with chronic diseases has been shown to improve medication adherence, few studies have evaluated its effects on the objective clinical outcomes. We investigated the impact of pharmacist intervention on medication adherence and clinical outcomes in patients with ulcerative colitis (UC). Methods Patients with UC and low medication adherence were divided into two groups, based on pharmacist intervention. Their medication possession ratio and nonadherence rate for 6 months before and after the baseline were investigated. The partial Mayo score, flare-up incidence, and factors influencing flare-up events for 1 year after the baseline were analyzed. Results Of 99 patients, 33 and 66 were included in the intervention and control groups, respectively. The nonadherence rate significantly declined in the intervention group 6 months after the baseline (60.6% before vs 30.3% after; p=0.013). The groups showed a significant difference regarding time-related partial Mayo scores (p=0.002). Intervention was significantly negatively correlated with time and the partial Mayo score (r2=0.035, p=0.013). A significant difference was observed in the flare-up incidence (33.3% in the intervention group vs 54.6% in the control group; p=0.046). Multivariate logistic regression indicated that pharmacist intervention (adjusted odds ratio, 0.370; 95% confidence interval, 0.145 to 0.945; p=0.038) independently reduced the flareup risk. Conclusions Pharmacist intervention significantly decreased the nonadherence rate, improved the partial Mayo score, and reduced the flare-up incidence compared with the control group in a cohort of UC patients identified to have low medication adherence.
Collapse
Affiliation(s)
- Jae Song Kim
- Department of Pharmacy, Severance Hospital, Yonsei University Health System, Seoul, Korea
- College of Pharmacy, Dongguk University Biomedi Campus, Goyang, Korea
| | - Min Jung Geum
- Department of Pharmacy, Severance Hospital, Yonsei University Health System, Seoul, Korea
| | - Eun Sun Son
- Department of Pharmacy, Severance Hospital, Yonsei University Health System, Seoul, Korea
- College of Pharmacy, Dongguk University Biomedi Campus, Goyang, Korea
| | - Yun Mi Yu
- Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Kyeng Hee Kwon
- College of Pharmacy, Dongguk University Biomedi Campus, Goyang, Korea
| |
Collapse
|
|
5
|
Iizuka M, Etou T, Sagara S. Efficacy of cytapheresis in patients with ulcerative colitis showing insufficient or lost response to biologic therapy. World J Gastroenterol 2022; 28:4959-4972. [PMID: 36160647 PMCID: PMC9494931 DOI: 10.3748/wjg.v28.i34.4959] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/16/2022] [Accepted: 08/17/2022] [Indexed: 02/06/2023] Open
Abstract
For the optimal management of refractory ulcerative colitis (UC), secondary loss of response (LOR) and primary non-response to biologics is a critical issue. This article aimed to summarize the current literature on the use of cytapheresis (CAP) in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations. Further, we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators (IM). Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM. There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM. Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies. Mean remission rates of biologics exposed or unexposed patients were 29.4 % and 44.2%, respectively. Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics. The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69% (mean: 48.0%, median: 42.9%) and 9%-75% (mean: 40.7%, median: 38%), respectively. CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics. Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics, these combination therapies induced clinical remission/response and steroid-free remission in more than 40% of patients with UC refractory to biologics on average. Given the excellent safety profile of CAP, this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics. Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.
Collapse
Affiliation(s)
- Masahiro Iizuka
- Akita Health Care Center, Akita Red Cross Hospital, Akita 010-0001, Japan
- Department of Gastroenterology, Akita Red Cross Hospital, Akita 010-1495, Japan
| | - Takeshi Etou
- Department of Gastroenterology, Akita Red Cross Hospital, Akita 010-1495, Japan
| | - Shiho Sagara
- Akita Health Care Center, Akita Red Cross Hospital, Akita 010-0001, Japan
| |
Collapse
|
|
6
|
Matsuoka K, Watanabe M, Ohmori T, Nakajima K, Ishida T, Ishiguro Y, Kanke K, Kobayashi K, Hirai F, Watanabe K, Mizusawa H, Kishida S, Miura Y, Ohta A, Kajioka T, Hibi T. AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Gastroenterol Hepatol 2022; 7:648-657. [PMID: 35366419 DOI: 10.1016/s2468-1253(22)00022-x] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 01/24/2022] [Accepted: 01/24/2022] [Indexed: 12/11/2022]
Affiliation(s)
- Katsuyoshi Matsuoka
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Toho University Sakura Medical Center, Sakura, Japan
| | - Mamoru Watanabe
- Tokyo Medical and Dental University, Advanced Research Institute and Department of Gastroenterology and Hepatology, Tokyo, Japan.
| | - Toshihide Ohmori
- Department of Gastroenterology, Ohmori Toshihide Gastro-intestinal Clinic, Ageo, Japan
| | - Koichi Nakajima
- Department of Gastrointestinal Division, Matsushima Clinic, Yokohama, Japan
| | - Tetsuya Ishida
- Department of IBD and Gastroenterology, Ishida Clinic of IBD and Gastroenterology, Oita, Japan
| | - Yoh Ishiguro
- Department of Gastroenterology and Hematology, National Hospital Organization Hirosaki National Hospital, Hirosaki, Japan
| | - Kazunari Kanke
- Gastrointestinal Division, Kanke Gastrointestinal Clinic, Utsunomiya, Japan
| | - Kiyonori Kobayashi
- Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara, Japan
| | - Fumihito Hirai
- Department of Gastroenterology and Medicine, Fukuoka University Hospital, Fukuoka, Japan
| | - Kenji Watanabe
- Division of Internal Medicine, Center for Inflammatory Bowel Disease, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hidehiro Mizusawa
- Department of Neurology, National Center of Neurology and Psychiatry Hospital, Tokyo, Japan
| | - Shuji Kishida
- Cranial Nerve Internal Medicine Department, Narita Tomisato Tokushukai Hospital, Tomisato, Japan
| | - Yoshiharu Miura
- Department of Neurology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Akira Ohta
- Clinical Development Department, EA Pharma, Tokyo, Japan
| | | | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| |
Collapse
|
|
7
|
Cai Z, Wang S, Li J. Treatment of Inflammatory Bowel Disease: A Comprehensive Review. Front Med (Lausanne) 2021; 8:765474. [PMID: 34988090 PMCID: PMC8720971 DOI: 10.3389/fmed.2021.765474] [Citation(s) in RCA: 233] [Impact Index Per Article: 58.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 11/29/2021] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD), as a global disease, has attracted much research interest. Constant research has led to a better understanding of the disease condition and further promoted its management. We here reviewed the conventional and the novel drugs and therapies, as well as the potential ones, which have shown promise in preclinical studies and are likely to be effective future therapies. The conventional treatments aim at controlling symptoms through pharmacotherapy, including aminosalicylates, corticosteroids, immunomodulators, and biologics, with other general measures and/or surgical resection if necessary. However, a considerable fraction of patients do not respond to available treatments or lose response, which calls for new therapeutic strategies. Diverse therapeutic options are emerging, involving small molecules, apheresis therapy, improved intestinal microecology, cell therapy, and exosome therapy. In addition, patient education partly upgrades the efficacy of IBD treatment. Recent advances in the management of IBD have led to a paradigm shift in the treatment goals, from targeting symptom-free daily life to shooting for mucosal healing. In this review, the latest progress in IBD treatment is summarized to understand the advantages, pitfalls, and research prospects of different drugs and therapies and to provide a basis for the clinical decision and further research of IBD.
Collapse
Affiliation(s)
- Zhaobei Cai
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
- Department of Gastroenterology and Hepatology, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Shu Wang
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Jiannan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
8
|
Cichoż-Lach H, Michalak A, Kopertowska-Majchrzak M, Eder P, Stawczyk-Eder K, Waszak K, Talar-Wojnarowska R, Zatorski H, Solarska-Półchłopek A, Chmielnicki J, Filip R, Pękala A, Janiak M, Skrobot K, Kasińska E, Krogulecki M, Królikowski P, Kłopocka M, Liebert A, Poniewierka E, Smoła I, Gąsiorowska A, Kaczka A, Wypych J, Wojciechowski K, Drygała S, Zagórowicz E. Characteristics of patients with moderate-to-severe ulcerative colitis treated with vedolizumab: results from a Polish multicenter, prospective, observational real-life study (the POLONEZ study). Therap Adv Gastroenterol 2021; 14:17562848211036456. [PMID: 34484422 PMCID: PMC8411627 DOI: 10.1177/17562848211036456] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 07/12/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Vedolizumab, a humanized antibody targeting the α4β7 integrin, was proven to be effective in the treatment of moderate-to-severe ulcerative colitis (UC) in randomized clinical trials. The aim of the POLONEZ study is to determine the demographic and clinical characteristics of the patients with UC treated with vedolizumab within the scope of the National Drug Program in Poland and to assess the real-world effectiveness and safety of vedolizumab in the study population. Here we report the demographic and clinical characteristics of these patients. METHODS This prospective study included adult patients eligible for UC treatment with vedolizumab who were recruited from 12 centers in Poland between February and November 2019. Collected data included sex, age, disease duration, presence of extraintestinal manifestations or comorbidities, status of previous biologic treatment, and current concomitant treatment. Disease extent was determined according to the Montreal classification, and disease activity was measured with the Mayo Score. RESULTS A total of 100 (55 biologic-naïve and 45 biologic-exposed) patients were enrolled in the study (51% female, median age 35 years). Among biologic-exposed patients (mostly infliximab-treated), 57% had failed to respond to the therapy. The disease duration was significantly shorter in biologic-naïve (median 5 years) than in biologic-exposed (8 years, p = 0.004) or biofailure patients (7 years, p = 0.04). In the overall population the median Total Mayo Score was 10. Disease extent and activity were similar between the subgroups. CONCLUSIONS Our study indicates that patients treated with vedolizumab in Poland receive the drug relatively early after UC diagnosis, but their disease is advanced. More than half of the patients had not been treated with biologic drugs before initiating vedolizumab. The study was registered in ENCePP database (EUPAS34119). LAY SUMMARY Characteristics of patients treated for ulcerative colitis with vedolizumab in Poland Treatment of moderate-to-severe ulcerative colitis (UC) with the integrin antagonist vedolizumab became available within the Polish National Drug Program (NDP) in 2018. In this study, for the first time, we provide detailed demographic and clinical characteristics of 100 patients (median age 35 years, 51% female) treated with vedolizumab in Poland, of whom 55 were biologic-naïve and 45 biologic-exposed. The median duration of disease was 6 years. The disease duration was shorter in biologic-naïve than in biologic-exposed patients. Most patients were affected by extensive colitis (52%) or left-sided colitis (42%). Median disease activity was 10 according to the Total Mayo Score. Sixty-eight patients received concomitant systemic corticosteroids and 45 patients received immunomodulators. Our findings indicate that Polish patients receiving vedolizumab have a high disease activity and are treated relatively early after UC diagnosis. This might be due to the criteria for inclusion of a patient in the NDP.
Collapse
Affiliation(s)
- Halina Cichoż-Lach
- Department of Gastroenterology, Medical
University of Lublin, Lublin, Poland
| | - Agata Michalak
- Department of Gastroenterology, Medical
University of Lublin, Lublin, Poland
| | | | - Piotr Eder
- Department of Gastroenterology, Dietetics, and
Internal Diseases, Poznan University of Medical Sciences, H. Święcicki
University Hospital, Poznaņ, Poland
| | - Kamila Stawczyk-Eder
- Department of Gastroenterology, Dietetics, and
Internal Diseases, Poznan University of Medical Sciences, H. Święcicki
University Hospital, Poznaņ, Poland
| | - Katarzyna Waszak
- Department of Gastroenterology, Dietetics, and
Internal Diseases, Poznan University of Medical Sciences, H. Święcicki
University Hospital, Poznaņ, Poland
| | | | - Hubert Zatorski
- Department of Digestive Tract Diseases, Medical
University of Lodz, Łódź, Poland
| | - Anna Solarska-Półchłopek
- Department of Gastroenterology, The Maria
Sklodowska-Curie National Research Institute of Oncology, Warsaw,
Poland,Department of Gastroenterology, Hepatology and
Clinical Oncology, The Medical Center of Postgraduate Education, Warsaw,
Poland
| | | | - Rafał Filip
- Department of Gastroenterology with IBD Unit,
Clinical Hospital No. 2, Rzeszów, Poland
| | - Anna Pękala
- Department of Gastroenterology with IBD Unit,
Clinical Hospital No. 2, Rzeszów, Poland
| | - Maria Janiak
- Department of Gastroenterology and Hepatology,
Medical University of Gdańsk, Gdańsk, Poland
| | - Krzysztof Skrobot
- Department of Gastroenterology and Hepatology,
Medical University of Gdańsk, Gdańsk, Poland
| | - Ewa Kasińska
- Department of Gastroenterology, Military
Institute of Medicine, Warsaw, Poland
| | - Michał Krogulecki
- Department of Gastroenterology, Military
Institute of Medicine, Warsaw, Poland
| | - Piotr Królikowski
- Department of Gastroenterology, Military
Institute of Medicine, Warsaw, Poland
| | - Maria Kłopocka
- Department of Gastroenterology and Nutritional
Disorders, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in
Toruń, Bydgoszcz, Poland
| | - Ariel Liebert
- Department of Gastroenterology and Nutritional
Disorders, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in
Toruń, Bydgoszcz, Poland
| | - Elżbieta Poniewierka
- Department of Gastroenterology and Hepatology,
Wrocław Medical University, Wrocław, Poland
| | - Izabela Smoła
- Department of Gastroenterology and Hepatology,
Wrocław Medical University, Wrocław, Poland
| | - Anita Gąsiorowska
- Department of Gastroenterology, University
Clinical Hospital Military Memorial Medical Academy—Central Veterans’
Hospital, Łódź, Poland
| | - Aleksandra Kaczka
- Department of Gastroenterology, University
Clinical Hospital Military Memorial Medical Academy—Central Veterans’
Hospital, Łódź, Poland
| | - Joanna Wypych
- Department of Gastroenterology, Surgery and
Nutrition, Copernicus Hospital, Gdańsk, Poland
| | | | | | - Edyta Zagórowicz
- Department of Gastroenterology, The Maria
Sklodowska-Curie National Research Institute of Oncology, Warsaw,
Poland,Department of Gastroenterology, Hepatology and
Clinical Oncology, The Medical Center of Postgraduate Education, Warsaw,
Poland
| |
Collapse
|
|
9
|
Iizuka M, Etou T, Shimodaira Y, Hatakeyama T, Sagara S. Cytapheresis re-induces high-rate steroid-free remission in patients with steroid-dependent and steroid-refractory ulcerative colitis. World J Gastroenterol 2021; 27:1194-1212. [PMID: 33828394 PMCID: PMC8006096 DOI: 10.3748/wjg.v27.i12.1194] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 02/11/2021] [Accepted: 03/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND It is a crucial issue for patients with refractory ulcerative colitis (UC), including steroid-dependent and steroid-refractory patients, to achieve and maintain steroid-free remission. However, clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient. Cytapheresis (CAP) is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects. This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients. AIM To clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients. METHODS We retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP. We analyzed the following points: (1) Efficacy of the first course of CAP; (2) Efficacy of the second, third, and fourth courses of CAP in patients who experienced relapses during the observation period; (3) Efficacy of CAP in colonic mucosa; and (4) Long-term efficacy of CAP. Clinical efficacy was evaluated using Lichtiger's clinical activity index or Sutherland index (disease activity index). Mucosal healing was evaluated using Mayo endoscopic subscore. The primary and secondary endpoints were the rate of achievement of steroid-free remission and the rate of sustained steroid-free remission, respectively. Statistical analysis was performed using the paired t-test and chi-squared test. RESULTS The rates of clinical remission, steroid-free remission, and poor effectiveness after CAP were 69.1%, 45.5%, and 30.9%, respectively. There were no significant differences in rate of steroid-free remission between patients with steroid-dependent and steroid-refractory UC. The mean disease activity index and Lichtiger's clinical activity index scores were significantly decreased after CAP (P < 0.0001). The rates of steroid-free remission after the second, third, and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%, 83.3%, and 60%, respectively. Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP. The rates of sustained steroid-free remission were 68.0%, 60.0%, and 56.0% at 12, 24, and 36 mo after the CAP. Nine patients (36%) had maintained steroid-free remission throughout the observation period. CONCLUSION Our results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.
Collapse
Affiliation(s)
- Masahiro Iizuka
- Akita Health Care Center, Akita Red Cross Hospital, Akita 010-0001, Japan
- Department of Gastroenterology, Akita Red Cross Hospital, Akita 010-1495, Japan
| | - Takeshi Etou
- Department of Gastroenterology, Akita Red Cross Hospital, Akita 010-1495, Japan
| | - Yosuke Shimodaira
- Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine, Akita 010-8543, Japan
| | - Takashi Hatakeyama
- Department of Nephrology, Akita Red Cross Hospital, Akita 010-1495, Japan
| | - Shiho Sagara
- Akita Health Care Center, Akita Red Cross Hospital, Akita 010-0001, Japan
| |
Collapse
|
|
10
|
Murakami Y, Fujiya M, Konishi H, Isozaki S, Sugiyama Y, Kobayashi Y, Sasaki T, Kunogi T, Takahashi K, Ando K, Ueno N, Kashima S, Moriichi K, Tanabe H, Okumura T. The Optimal Dose of Tacrolimus in Combination Therapy with an Anti-TNFα Antibody in a Mouse Colitis Model. Biol Pharm Bull 2021; 44:564-570. [PMID: 33790106 DOI: 10.1248/bpb.b20-00916] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
An attempt to use combination therapy with anti-tumor necrosis factor α (TNFα) antibodies and tacrolimus (TAC) has been tried to induce remission in ulcerative colitis (UC). However, the optimal dose of TAC in combination therapy with anti-TNFα antibodies (TAC + anti-TNFα therapy) remains unclear. We examined the efficacy of various doses of TAC + anti-TNFα therapy in a mouse colitis model. Dextran sulfate sodium induced colitis model mice were divided into an anti-TNFα antibody monotherapy group and the groups that received various doses of TAC + anti-TNFα therapy. The nuclear factor expression of activated T-cells, cytoplasmic 1 (NFATc1) in the nuclei and the mRNA expression of inflammatory cytokines were assessed by immunohistochemistry and RT-PCR, respectively. The serum anti-TNFα antibody concentration was measured with an enzyme-linked immunosorbent assay. The colon length and histological severity were significantly improved in the groups that received any dose of TAC + anti-TNFα therapy. The nuclear expression of NFATc1 was inversely proportional to the administered doses of TAC. The expression levels of inflammatory cytokines tended to decrease in proportion to the dose of TAC. The serum concentration of anti-TNFα antibodies in the high-dose TAC + anti-TNFα therapy was significantly higher than those in the other groups. Low-dose TAC exerted its immunosuppressive effect on T-cells, and additionally, high-dose TAC maintained the serum anti-TNFα antibody concentration. When administered in combination with anti-TNFα antibodies, the dose of TAC should be adjusted according to the disease severity.
Collapse
Affiliation(s)
- Yuki Murakami
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Mikihiro Fujiya
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
- Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University
| | - Hiroaki Konishi
- Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University
| | - Shotaro Isozaki
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Yuya Sugiyama
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Yu Kobayashi
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Takahiro Sasaki
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Takehito Kunogi
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Keitaro Takahashi
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Katsuyoshi Ando
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Nobuhiro Ueno
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Shin Kashima
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Kentaro Moriichi
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Hiroki Tanabe
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| | - Toshikatsu Okumura
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University
| |
Collapse
|
|
11
|
Effects of Apremilast, an Oral Inhibitor of Phosphodiesterase 4, in a Randomized Trial of Patients With Active Ulcerative Colitis. Clin Gastroenterol Hepatol 2020; 18:2526-2534.e9. [PMID: 31926340 DOI: 10.1016/j.cgh.2019.12.032] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 12/23/2019] [Accepted: 12/26/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS New oral therapeutic agents are needed for patients with ulcerative colitis (UC) who are unresponsive or intolerant to conventional therapy. METHODS We performed a double-blind, phase 2 trial of adults with active UC for 3 months or more who were naïve to biologic therapy or had been failed by, could not tolerate, or had contraindications to conventional therapies. The study was performed at 61 sites in 14 countries (screening from January 2015 through May 2017). Patients were randomly assigned to groups given apremilast 30 mg (n = 57), apremilast 40 mg (n = 55), or placebo (n = 58) twice daily for 12 weeks; patients were then randomly assigned to groups that received apremilast, 30 or 40 mg twice daily, for an additional 40 weeks. Endoscopies were performed and biopsies were collected during the screening phase, at week 12, and at week 52. Blood and fecal samples were also collected and analyzed throughout the study. The primary endpoint was clinical remission at week 12, defined as a total Mayo score of 2 or less, with no individual subscore above 1. RESULTS Clinical remission was achieved at week 12 by 31.6% of patients in the 30 mg apremilast group and 12.1% of patients in the placebo group (P = .01). However, only 21.8% of patients in the 40 mg apremilast group achieved clinical remission at week 12 (P = .27 compared with placebo). Differences in clinical remission between the 30 mg and 40 mg apremilast groups were associated with differences in endoscopic improvement. Both apremilast groups had similar improvements from baseline in Mayo score components (stool frequency score, rectal bleeding score, physician's global assessment). The 30 mg and 40 mg apremilast groups had greater median percent reductions in C-reactive protein (measured by a high-sensitivity blood test) and fecal calprotectin through week 12 than the placebo group. At week 52, clinical remission was achieved by 40.4% of patients initially assigned to the apremilast 30 mg group and 32.7% of patients initially assigned to the apremilast 40 mg group. The most frequent apremilast-associated adverse events were headache and nausea. CONCLUSIONS Although the primary endpoint of clinical remission was not met in this phase 2 trial, a greater proportion of patients with active UC who received apremilast (30 mg or 40 mg) had improvements in clinical and endoscopic features, and markers of inflammation, at 12 weeks. Clinical remission was maintained to week 52 in up to 40% of patients who continued apremilast until that time point. ClinicalTrials.gov no: NCT02289417.
Collapse
|
|
12
|
Kakimoto K, Matsuura M, Fukuchi T, Hongo H, Kimura T, Aoyama N, Okuda Y, Aomatsu K, Kamata N, Yokoyama Y, Mizuno C, Inoue T, Miyazaki T, Nakamura S, Higuchi K, Nakase H. Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial. CROHNS & COLITIS 360 2020; 2:otaa073. [PMID: 34192247 PMCID: PMC7797742 DOI: 10.1093/crocol/otaa073] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Indexed: 12/20/2022]
Abstract
Background Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. Methods We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. Results The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. Conclusions GMA shows effectiveness in inducing remission in UC patients not receiving steroid. EXPECT study demonstrates that granulocyte and monocyte adsorptive apheresis has promising effectiveness with regard to inducing remission in patients with active ulcerative colitis (UC) who are not receiving steroid treatment. The first episode of UC was an independent predictor of a response in multiple logistic regression.
Collapse
Affiliation(s)
- Kazuki Kakimoto
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Takumi Fukuchi
- Department of Gastroenterology and Hepatology, Iseikai Hospital, Osaka, Osaka, Japan
| | - Hitoshi Hongo
- Department of Gastroenterology, Fujita Gastroenterological Hospital, Takatsuki, Osaka, Japan
| | - Tsuguhiro Kimura
- Department of Gastroenterology, Fujita Gastroenterological Hospital, Takatsuki, Osaka, Japan
| | - Nobuo Aoyama
- Department of Gastroenterology, Gastrointestinal Endoscopy and IBD Center, Aoyama Medical Clinic, Kobe, Hyogo, Japan
| | - Yorihide Okuda
- Department of Gastroenterology, Otemae Hospital, Osaka, Osaka, Japan
| | - Kazuki Aomatsu
- Department of Gastroenterology, Izumiotsu Municipal Hospital, Izumiotsu, Osaka, Japan
| | - Noriko Kamata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Yoko Yokoyama
- Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Chiemi Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Osaka, Japan
| | - Takuya Inoue
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Takako Miyazaki
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Shiro Nakamura
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Kazuhide Higuchi
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan
| |
Collapse
|
|
13
|
Kitayama M, Akazawa Y, Yoshikawa D, Higashi S, Morisaki T, Oda H, Ikeda M, Nakashima Y, Tabuchi M, Hashiguchi K, Matsushima K, Yamaguchi N, Kondo H, Nakao K, Takeshima F. Comparative efficacy of antitumor necrosis factor agents and tacrolimus in naïve steroid-refractory ulcerative colitis patients. Sci Rep 2020; 10:12546. [PMID: 32719413 PMCID: PMC7385627 DOI: 10.1038/s41598-020-68828-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 07/02/2020] [Indexed: 02/07/2023] Open
Abstract
While retrospective studies have compared the efficacy of anti–tumour necrosis factor (TNF) agents and tacrolimus (TAC) in ulcerative colitis (UC), information regarding first-time use of these agents is limited. The aim of our study was to investigate the short- and long-term efficacy of anti-TNF agents [adalimumab (ADA) and infliximab (IFX)] and TAC in anti-TNF agent- and TAC-naïve steroid-refractory UC patients. We evaluated 150 steroid-refractory UC patients receiving anti-TNF agents (IFX: n = 30, ADA: n = 41) or TAC (n = 79) at eight institutions in Japan. Clinical response rates at 8 weeks were 73.2% and 75.9% while remission rates were 30.1% and 25.3% in the anti-TNF and TAC groups, respectively. Logistic regression analysis showed the male sex and higher C-reactive protein to be independent factors for response to anti-TNF agents and TAC, respectively. Use of TAC was an independent factor for relapse. No differences in response to the treatment or relapse were observed between IFX and ADA. In conclusion, TAC and anti-TNF agents promoted similar short-term effects, but anti-TNF agents ensured better long-term outcomes at first-time treatment of steroid-refractory UC patients.
Collapse
Affiliation(s)
- Moto Kitayama
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Yuko Akazawa
- Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Japan
| | - Daisuke Yoshikawa
- Department of Gastroenterology and Hepatology, Sasebo City General Hospital, 9-3 Hirase-cho, Sasebo City, Nagasaki, 857-8511, Japan
| | - Shuntaro Higashi
- Department of Gastroenterology, Inoue Hospital, 6-12, Takaramachi, Nagasaki City, Nagasaki, 850-0045, Japan
| | - Tomohito Morisaki
- Department of Gastroenterology and Hepatology, National Hospital Organization Ureshino Medical Center, 2436 Ureshino-cho, Ureshino City, Saga, 843-0393, Japan
| | - Hidetoshi Oda
- Department of Gastroenterology and Hepatology, Sasebo Chuo Hospital, 15 Yamato-cho, Sasebo City, Nagasaki, 857-1195, Japan
| | - Maho Ikeda
- Department of Internal Medicine, Juko Memorial Nagasaki Hospital, 6-17, Maruo, Nagasaki City, Nagasaki, 852-8004, Japan
| | - Yujiro Nakashima
- Department of Gastroenterology, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Ohmura City, Nagasaki, 856-8562, Japan
| | - Maiko Tabuchi
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Keiichi Hashiguchi
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Kayoko Matsushima
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Naoyuki Yamaguchi
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Hisayoshi Kondo
- Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Fuminao Takeshima
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan. .,Department of Internal Medicine, Nagasaki Prefecture Goto Central Hospital, 205 Yoshikugi, Goto City, Nagasaki, 853-0031, Japan.
| |
Collapse
|
|
14
|
Sood A, Ahuja V, Midha V, Sinha SK, Pai CG, Kedia S, Mehta V, Bopanna S, Abraham P, Banerjee R, Bhatia S, Chakravartty K, Dadhich S, Desai D, Dwivedi M, Goswami B, Kaur K, Khosla R, Kumar A, Mahajan R, Misra SP, Peddi K, Singh SP, Singh A. Colitis and Crohn's Foundation (India) consensus statements on use of 5-aminosalicylic acid in inflammatory bowel disease. Intest Res 2020; 18:355-378. [PMID: 32646198 PMCID: PMC7609395 DOI: 10.5217/ir.2019.09176] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 04/04/2020] [Indexed: 12/16/2022] Open
Abstract
Despite several recent advances in therapy in inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) therapy has retained its place especially in ulcerative colitis. This consensus on 5-ASA is obtained through a modified Delphi process, and includes guiding statements and recommendations based on literature evidence (randomized trials, and observational studies), clinical practice, and expert opinion on use of 5-ASA in IBD by Indian gastroenterologists. The aim is to aid practitioners in selecting appropriate treatment strategies and facilitate optimal use of 5-ASA in patients with IBD.
Collapse
Affiliation(s)
- Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, India
| | - Saroj Kant Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - C Ganesh Pai
- Department of Gastroenterology, Kasturba Medical College, Manipal, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | | | - Philip Abraham
- P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - Rupa Banerjee
- Asian Institute of Gastroenterology, Hyderabad, India
| | - Shobna Bhatia
- Department of Gastroenterology, King Edward Memorial Hospital, Mumbai, India
| | | | - Sunil Dadhich
- Department of Gastroenterology, Dr. Sampurnanand Medical College, Jodhpur, India
| | - Devendra Desai
- P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - Manisha Dwivedi
- Department of Gastroenterology, Moti Lal Nehru Medical College, Allahabad, India
| | - Bhabhadev Goswami
- Department of Gastroenterology, Gauhati Medical College, Guwahati, India
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Rajeev Khosla
- Max Super Speciality Hospital, Saket, New Delhi, India
| | - Ajay Kumar
- BLK Super Speciality Hospital, New Delhi, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - S P Misra
- Department of Gastroenterology, Moti Lal Nehru Medical College, Allahabad, India
| | - Kiran Peddi
- Citizens Centre for Digestive Disorders, Hyderabad, India
| | - Shivaram Prasad Singh
- Department of Gastroenterology, Sriram Chandra Bhanj Medical College and Hospital, Cuttack, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| |
Collapse
|
|
15
|
Ito A, Murasugi S, Omori T, Nakamura S, Tokushige K. Relationship between mucosal healing by tacrolimus and relapse of refractory ulcerative colitis: a retrospective study. BMC Gastroenterol 2020; 20:203. [PMID: 32590945 PMCID: PMC7320561 DOI: 10.1186/s12876-020-01317-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 05/22/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Tacrolimus (TAC) is a powerful remission-inducing drug for refractory ulcerative colitis (UC). However, it is unclear whether mucosal healing (MH) influences relapse after completion of TAC.We investigated whether MH is related to relapse after TAC. PATIENTS Among 109 patients treated with TAC, 86 patients achieved clinical remission and 55 of them underwent colonoscopy at the end of TAC. These 55 patients were investigated. METHODS Patients with MH at the end of TAC were classified into the MH group (n = 41), while patients without MH were classified into the non-MH group (n = 14). These groups were compared with respect to 1) clinical characteristics before treatment, 2) clinical characteristics on completion of treatment, and 3) the relapse rate and adverse events rates. This is a retrospective study conducted at a single institution. RESULTS 1) There was a significant difference in baseline age between the two groups before TAC therapy, but there were no significant differences in other clinical characteristics. The NMH group was younger (MH group: 48.1 (23-79) years, NMH group: 36.3 (18-58) years, P = 0.007). Endoscopic scores showed significant differences between the 2 groups at the end of TAC. There were also significant differences in the steroid-free rate after 24 weeks (MH group: 85.3%, NMH group 50%, P = 0.012). There was no significant difference in the relapse rate between the 2 groups at 100 days after remission, but a significant difference was noted at 300 days (17% vs. 43%), 500 days (17% vs. 75%), and 1000 days (17% vs. 81%) (all P < 0.05). CONCLUSIONS TAC is effective for refractory ulcerative colitis. However, even if clinical remission is achieved, relapse is frequent when colonoscopy shows that MH has not been achieved. It is important to evaluate the mucosal response by colonoscopy on completion of TAC.
Collapse
Affiliation(s)
- Ayumi Ito
- Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Syun Murasugi
- Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Teppei Omori
- Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Shinichi Nakamura
- Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Katsutoshi Tokushige
- Department of Gastroenterology, Tokyo Women's Medical University, Kawada-cho 8-1 Shinjuku-ku, Tokyo, 162-8666, Japan
| |
Collapse
|
|
16
|
Long MD, Smith TW, Dibonaventura M, Gruben D, Bargo D, Salese L, Quirk D. Real-world Effectiveness of Advanced Therapies Among Patients With Moderate to Severe Ulcerative Colitis in the United States. Inflamm Bowel Dis 2020; 26:941-948. [PMID: 31560046 PMCID: PMC7216775 DOI: 10.1093/ibd/izz204] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) treatment aims to induce response and maintain steroid-free remission. For patients with moderate to severe UC and/or nonresponse to conventional treatment, advanced therapies (immunosuppressants and biologics) are available. We assessed real-world effectiveness of advanced UC therapies. METHODS This retrospective analysis of claims data included adult patients with UC initiating immunosuppressant or biologic therapy, with 12 months' continuous enrollment pre- and postinitiation. Patients had no prescription for biologic therapy (and/or immunosuppressant if initiating immunosuppressant) in the previous 12 months. Proportion of patients remaining steroid-free (excluding 14-week tapering period), hospitalizations, and costs in the 12 months postinitiation were assessed. RESULTS In total, 3562 patients were included in the analysis. Most patients (83.0%) used steroids in the 12 months before initiating advanced therapy. Overall, 47.8% remained steroid-free after 12 months (excluding tapering). After adjusting for patient characteristics, remaining steroid-free was significantly more likely with infliximab (43.9%) than with adalimumab (39.4%; P < 0.05); golimumab (38.2%) and vedolizumab (41.4%) were not significantly different vs adalimumab. Overall, 12.2% of patients had a UC-related hospitalization within 12 months of initiation, with a mean (SD) total length of stay of 8.2 (8.9) days and no significant differences between biologic therapies. Mean, unadjusted, UC-related costs in the 12 months postinitiation were $42,579 and were similar between therapies. CONCLUSIONS Patients with UC initiating advanced therapy frequently continued using steroids for at least a year. Some patients experienced extended UC-related hospitalizations, with high UC-related costs overall. This suggests an ongoing challenge in managing patients with moderate to severe UC.
Collapse
Affiliation(s)
- Millie D Long
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | | | | | | | | | | | | |
Collapse
|
|
17
|
Khan N, Trivedi C, Shah Y, Cole E, Lewis J, Yang YX. The Natural History of Newly Diagnosed Ulcerative Colitis in Patients with Concomitant Primary Sclerosing Cholangitis. Inflamm Bowel Dis 2018; 24:2062-2067. [PMID: 29697792 DOI: 10.1093/ibd/izy106] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Primary sclerosing cholangitis (PSC) is commonly associated with ulcerative colitis (UC). Our aim was to compare the course of disease in patients with UC-PSC and UC alone in a nationwide cohort. METHODS We conducted a retrospective cohort study among nation-wide Veterans Affairs (VA) patients newly diagnosed with UC to determine the association between PSC status and clinical outcomes related to UC disease course. This study was divided into 2 groups of patients: (1) The incident UC-PSC group and (2) the incident UC-alone group. Follow-up began at the time of index colonoscopy that diagnosed UC and ended at the first occurrence of the respective outcome for the regression analysis of the following censoring events: (1) colectomy, (2) death, (3) end of follow-up, and (4 lost to follow-up. RESULTS The analysis included 836 UC patients without PSC and 74 UC-PSC patients. In univariate comparisons, PSC patients were more likely to have more extensive UC than those without PSC. In a multivariable Cox regression analysis adjusting for sex, age at UC diagnosis, race, severity of UC, and extent of UC, PSC status was not associated with the risk of colectomy for UC, increased risk of receiving ≥ 2 courses of steroids for UC, or with the risk of receiving immunomodulators for UC. CONCLUSION UC-PSC patients do not have a more benign disease course than UC patients without PSC. UC-PSC patients may have a modestly increased risk for multiple courses of steroids, which may be mediated by more extensive colonic involvement.
Collapse
Affiliation(s)
- Nabeel Khan
- Section of Gastroenterology, Corporal Michael J. Crescenz Medical Center, Pennsylvania, USA.,Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Guardian Drive, PA, USA
| | - Chinmay Trivedi
- Section of Gastroenterology, Corporal Michael J. Crescenz Medical Center, Pennsylvania, USA
| | - Yash Shah
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, James J. Peters VA Medical Center, NY, USA
| | - Elisabeth Cole
- Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, PA, USA
| | - James Lewis
- Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Yu-Xiao Yang
- Section of Gastroenterology, Corporal Michael J. Crescenz Medical Center, Pennsylvania, USA.,Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Guardian Drive, PA, USA
| |
Collapse
|
|
18
|
Barreiro-Alonso E, Saro-Gismera C, Sánchez M. Outcomes and prediction of corticosteroid therapy after successive courses of ulcerative colitis treatments. Expert Rev Gastroenterol Hepatol 2018; 12:733-741. [PMID: 29911903 DOI: 10.1080/17474124.2018.1489231] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) may require systemic corticosteroid (CS) treatment often without a reliable predictable response, except the Ho-index, used to predict severe cases. The present study aims to determine CS-efficacy and CS-free remission for different courses and longer follow-ups, and a predictive value of CS-outcomes, by the Ho-index and the analysis of clinical variables. METHODS An observational retrospective study performed with 136 patients was based on clinical and analytical characteristics, before successive CS-therapies. RESULTS The age of UC onset showed three peaks. After the first course, 55.6% were CS-responders, and 39% had CS-free remission by the 3-5-year follow-up. Successive CS-courses presented less efficacy and CS-free remissions, associated with increased CS-use dependence. The Ho-index might only predict the first course of CS and low-score patients with severe UC. Logistic regression analysis gave a predictive response mainly due to the age at diagnosis, the interval from diagnosis to CS-therapy, and C-reactive protein (CRP) or hemoglobin values. CONCLUSIONS One-third of the cases were CS-free remission UC. Successive courses showed decreased efficacy and increased CS-dependence, limiting CS-treatment. An older age at diagnosis, longer interval from diagnosis to CS-therapy, lower CRP and higher hemoglobin predicted better prognosis. The accuracy of prediction should be validated and include additional markers.
Collapse
Affiliation(s)
- Eva Barreiro-Alonso
- a Sección de Aparato Digestivo , Hospital Universitario de Cabueñes , Gijón , Spain
| | | | - Manuel Sánchez
- b Farmacología, Departamento de Medicina , Universidad de Oviedo; Instituto Universitario de Oncología del Principado de Asturias (IUOPA) , Oviedo , Spain
| |
Collapse
|
|
19
|
Corticosteroid Sparing in Inflammatory Bowel Disease is More Often Achieved in the Immunomodulator and Biological Era-Results from the Dutch Population-Based IBDSL Cohort. Am J Gastroenterol 2018; 113:384-395. [PMID: 29317770 DOI: 10.1038/ajg.2017.482] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 11/14/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Corticosteroid-free remission is an emerging treatment goal in the management of inflammatory bowel disease (IBD). In the population-based Inflammatory Bowel Disease South Limburg cohort, we studied temporal changes in corticosteroid use and assessed the corticosteroid-sparing effects of immunomodulators and biologicals in real life. METHODS In total, 2,823 newly diagnosed patients with Crohn's disease (CD) or ulcerative colitis (UC) were included. Corticosteroid exposure and cumulative days of use were compared between patients diagnosed in 1991-1998 (CD: n=316, UC: n=539), 1999-2005 (CD: n=387, UC: n=527), and 2006-2011 (CD: n=459, UC: n=595). Second, the corticosteroid-sparing effects of immunomodulators and biologicals were assessed. RESULTS Over time, the corticosteroid exposure rate was stable (54.0% in CD and 31.4% in UC), even as the cumulative corticosteroid use in the first disease year (CD: 83 days (interquartile range (IQR) 35-189), UC: 62 days (IQR 0-137)). On the long-term, a gradual decrease in cumulative corticosteroid use was seen in CD (era '91-'98: 366 days (IQR 107-841), era '06-'11: 120 days (IQR 72-211), P<0.01), whereas in UC an initial decrease was observed (era '91-'98: 184 days (IQR 86-443), era '99-'05: 166 days (IQR 74-281), P=0.03), and stabilization thereafter. Immunomodulator and biological users had a lower risk of requiring corticosteroids than matched controls in CD only (33.6% vs. 49.9%, P<0.01, and 25.7% vs. 38.2%, P=0.04, respectively). CONCLUSIONS In a real-world setting, more recently diagnosed IBD patients used lower amounts of corticosteroids as of the second year of disease. For CD, a significant association was found with the use of immunomodulators and biologicals. These conclusions support the increasing use of these treatment modalities.
Collapse
|
|
20
|
Khan N, Patel D, Shah Y, Trivedi C, Yang YX. Albumin as a prognostic marker for ulcerative colitis. World J Gastroenterol 2017; 23:8008-8016. [PMID: 29259376 PMCID: PMC5725295 DOI: 10.3748/wjg.v23.i45.8008] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 10/10/2017] [Accepted: 10/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the role of albumin at the time of ulcerative colitis (UC) diagnosis in predicting the clinical course of disease. METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia (i.e., ≤ 3.5 gm/dL) or normal albumin levels (i.e., > 3.5 gm/dL) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined as albumin level ≤ 3.5 g/dL at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids (CS), thiopurines, anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients, but 92 (11.4%) patients did not have their albumin levels checked at the time of UC diagnosis, and they were excluded. A total of 710 patients, who had albumin levels checked at time of UC diagnosis, were included in our study. Amongst them, 536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use (adjusted HR = 1.7, 95%CI: 1.3-2.3), higher likelihood of thiopurine or anti- TNF use (adjusted HR = 1.72, 95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients, but it was not statistically significant (Adjusted HR = 1.7, 95%CI: 0.90-3.25). CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis.
Collapse
Affiliation(s)
- Nabeel Khan
- Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States
- Section of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, United States
| | - Dhruvan Patel
- Department of Gastroenterology, Drexel University College of Medicine, Philadelphia, PA 19102, United States
| | - Yash Shah
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, James J. Peters VA Medical Center, Bronx, NY 10468, United States
| | - Chinmay Trivedi
- Section of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, United States
| | - Yu-Xiao Yang
- Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States
- Section of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, United States
| |
Collapse
|
|
21
|
Fukuda T, Naganuma M, Sugimoto S, Nanki K, Mizuno S, Mutaguchi M, Nakazato Y, Inoue N, Ogata H, Iwao Y, Kanai T. The risk factor of clinical relapse in ulcerative colitis patients with low dose 5-aminosalicylic acid as maintenance therapy: A report from the IBD registry. PLoS One 2017; 12:e0187737. [PMID: 29108025 PMCID: PMC5673208 DOI: 10.1371/journal.pone.0187737] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Accepted: 10/25/2017] [Indexed: 12/18/2022] Open
Abstract
Background 5-Aminosalicylic acids (5-ASA) are effective for ulcerative colitis (UC) as a maintenance therapy. It is not clear when and how to reduce a dose of 5-ASA after inducing remission. We aimed to investigate the clinical characteristics and evaluate the risk factors of relapse for UC patients receiving 5-ASA. Methods The medical records of prospectively registered UC patients who received oral 5-ASA as maintenance therapy between January and December 31, 2014, were investigated. The patients’ clinical characteristics in a 2-year follow-up were compared between a relapse group and a remission group. Results Of 527 UC patients receiving only oral 5-ASA, 390 (74.0%) maintained remission and 137 (26.0%) relapsed during the follow-up period. Multivariable analysis indicated that a shorter duration of disease remission (p < 0.001, OR: 1.24, 95% CI: 1.12–1.38) was statistically significant for each comparison between the remission and relapse groups among all the patients. Risk factors for clinical relapse were a shorter duration of disease remission (p <0.001, OR: 1.17, 95% CI: 1.04–1.33) in the high-dose 5-ASA group and a shorter duration of disease remission (p = 0.003, OR: 1.45, 95% CI: 1.13–1.89) and a history of steroid use (p = 0.048, OR: 4.73, 95% CI: 1.01–22.2) in the low-dose group. Conclusions A dose reduction of 5-ASA might be cautiously selected in UC patients with a history of steroid use and a shorter duration of disease remission.
Collapse
Affiliation(s)
- Tomohiro Fukuda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Shinya Sugimoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Kosaku Nanki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Shinta Mizuno
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Makoto Mutaguchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Yoshihiro Nakazato
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
| | - Nagamu Inoue
- Center for Preventive Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Haruhiko Ogata
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
| | - Yasushi Iwao
- Center for Preventive Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
- * E-mail:
| |
Collapse
|
|
22
|
Kumar V, Shah Y, Patel D, Khan N. Elderly-Onset and Adult-Onset Ulcerative Colitis Are More Similar than Previously Reported in a Nationwide Cohort. Dig Dis Sci 2017; 62:2857-2862. [PMID: 28884254 DOI: 10.1007/s10620-017-4734-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Accepted: 08/22/2017] [Indexed: 12/30/2022]
Abstract
BACKGROUND Elderly-onset ulcerative colitis (EO-UC) is recognized as a distinct subpopulation of UC. To our knowledge, there have been no nationwide studies of EO-UC populations in the USA. AIMS We aim to characterize differences in presentation at diagnosis and clinical course between EO-UC and adult-onset UC (AO-UC) patients in a national cohort. METHODS Complete medical records of patients newly diagnosed with UC from October 2001 to October 2011 in the Veterans Affairs health system were obtained. Patients were followed until colectomy, death, or the end of the observation period on November 2015. EO-UC patients (age of diagnosis ≥65 years) were compared to AO-UC patients (age of diagnosis ≤40 years) with respect to demographic, severity, and therapeutic data. Statistical analysis was performed using JMP statistical software. RESULTS We identified 836 newly diagnosed UC patients, of which 207 had EO-UC and 102 had AO-UC. The mean age of diagnosis was 72.4 years (EO-UC) and 32.9 years (AO-UC), with a mean 8-year follow-up period. The incidence of pancolitis at the time of diagnosis was similar between both groups (p = 0.67). There was no difference in steroid use (36.7 vs 45.1%, p = 0.1563), thiopurine use (19.3 vs 22.6%, p = 0.5081), and colectomy rates (6.3 vs 5.9%, p = 0.8911) between EO-UC and AO-UC populations. There was lower anti-TNF use in EO-UC patients compared to AO-UC patients (5.8 vs 14.7%, p = 0.0091). CONCLUSION In this nationwide cohort, we found that the use of steroids, thiopurines, and colectomy was similar in both populations, while anti-TNF use was lower among the elderly.
Collapse
Affiliation(s)
- Vinayak Kumar
- Jordan Medical Education Center, Perelman School of Medicine, University of Pennsylvania, Building 421, Room 5-1009; 3400 Civic Center Boulevard, 6th Floor, Philadelphia, PA, 19104, USA.
| | - Yash Shah
- Department of Gastroenterology, Veterans Affairs Hospital, Philadelphia VA Medical Center, Room 430; 3900 Woodland Ave, Philadelphia, PA, 19104, USA
| | - Dhruvan Patel
- Department of Internal Medicine, Mercy Catholic Medical Center, 1500 Lansdowne Ave, Darby, PA, 19023, USA
| | - Nabeel Khan
- Jordan Medical Education Center, Perelman School of Medicine, University of Pennsylvania, Building 421, Room 5-1009; 3400 Civic Center Boulevard, 6th Floor, Philadelphia, PA, 19104, USA
- Department of Gastroenterology, Veterans Affairs Hospital, Philadelphia VA Medical Center, Room 430; 3900 Woodland Ave, Philadelphia, PA, 19104, USA
| |
Collapse
|
|
23
|
Khan N, Patel D, Shah Y, Lichtenstein G, Yang YX. A Novel User-Friendly Model to Predict Corticosteroid Utilization in Newly Diagnosed Patients with Ulcerative Colitis. Inflamm Bowel Dis 2017; 23:991-997. [PMID: 28328623 DOI: 10.1097/mib.0000000000001080] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Corticosteroid (CS) use is an important marker of poor prognosis in ulcerative colitis (UC). Our aim was to develop and validate a model to predict the risk of CS utilization over the course of disease in newly diagnosed patients with UC. METHODS Newly diagnosed patients with UC from a nationwide VA cohort were followed over time to evaluate factors predictive of CS use. Multivariate logistic regression was performed. Model development was performed in a random 2/3 of the total cohort and then validated in the remaining 1/3. The primary outcome was the use of CS for the management of UC. Candidate predictors included routinely available data at the time of UC diagnosis, including demographics, laboratory results, and index colonoscopy findings. RESULTS Six hundred ninety-nine eligible patients with UC were followed for a median duration of 8 years. Two hundred eighty-eight patients (41.2%) required CS use for the management of UC. Key predictors for CS utilization selected for the model were as follows: age, non-African American ethnicity, presence of hypoalbuminemia, and iron-deficiency anemia at the time of UC diagnosis, endoscopic extent, or severity of disease at index colonoscopy. Model discrimination was good (area under the receiver operator curve 0.71 [95% confidence interval, 0.66-0.76] for the model including baseline UC extent and 0.71 [95% confidence interval, 0.67-0.76]) for the model including baseline UC severity. Model calibration was consistently good in all models (Hosmer-Lemeshow goodness of fit P > 0.05). The models performed similarly in the internal validation cohort. CONCLUSIONS We developed and internally validated a novel prognostic model to predict CS use among patients with newly diagnosed UC.
Collapse
Affiliation(s)
- Nabeel Khan
- *Section of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; †Section of Gastroenterology, VA Medical Center, Philadelphia, Pennsylvania; and ‡Department of Internal Medicine, Mercy Catholic Medical Center, Darby, Pennsylvania
| | | | | | | | | |
Collapse
|
|
24
|
Khan N, Patel D, Shah Y, Yang YX. A Novel Model for Predicting Incident Moderate to Severe Anemia and Iron Deficiency in Patients with Newly Diagnosed Ulcerative Colitis. Dig Dis Sci 2017; 62:1295-1304. [PMID: 28285428 DOI: 10.1007/s10620-017-4512-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 02/25/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND Anemia and iron deficiency are common complications of ulcerative colitis (UC). We aimed to develop and internally validate a prediction model for the incidence of moderate to severe anemia and iron deficiency anemia (IDA) in newly diagnosed patients with UC. METHODS Multivariable logistic regression was performed among a nationwide cohort of patients who were newly diagnosed with UC in the VA health-care system. Model development was performed in a random two-third of the total cohort and then validated in the remaining one-third of the cohort. As candidate predictors, we examined routinely available data at the time of UC diagnosis including demographics, medications, laboratory results, and endoscopy findings. RESULTS A total of 789 patients met the inclusion criteria. For the outcome of moderate to severe anemia, age, albumin level and mild anemia at UC diagnosis were predictors selected for the model. The AUC for this model was 0.69 (95% CI 0.64-0.74). For the outcome of moderate to severe anemia with evidence of iron deficiency, the predictors included African-American ethnicity, mild anemia, age, and albumin level at UC diagnosis. The AUC was 0.76, (95% CI 0.69-0.82). Calibration was consistently good in all models (Hosmer-Lemeshow goodness of fit p > 0.05). The models performed similarly in the internal validation cohort. CONCLUSIONS We developed and internally validated a prognostic model for predicting the risk of moderate to severe anemia and IDA among newly diagnosed patients with UC. This will help identify patients at high risk of these complications, who could benefit from surveillance and preventive measures.
Collapse
Affiliation(s)
- Nabeel Khan
- Section of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, 722 Blockley Hall, Philadelphia, PA, 19104, USA.
- Section of Gastroenterology, Philadelphia VA Medical Center, Perelman School of Medicine at University of Pennsylvania, 3900 Woodland Avenue, Philadelphia, PA, 19104, USA.
| | - Dhruvan Patel
- Department of Internal Medicine, Mercy Catholic Medical Center, 1500 Lansdowne Ave, Darby, PA, 19023, USA
| | - Yash Shah
- Section of Gastroenterology, Philadelphia VA Medical Center, Perelman School of Medicine at University of Pennsylvania, 3900 Woodland Avenue, Philadelphia, PA, 19104, USA
| | - Yu-Xiao Yang
- Section of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, 722 Blockley Hall, Philadelphia, PA, 19104, USA
| |
Collapse
|
|
25
|
Rai T, Choudhury BN, Kedia S, Bopanna S, Venigalla PM, Garg SK, Singla V, Makharia G, Ahuja V. Short-Term Clinical Response to Corticosteroids Can Predict Long-Term Natural History of Ulcerative Colitis: Prospective Study Experience. Dig Dis Sci 2017; 62:1025-1034. [PMID: 28161855 DOI: 10.1007/s10620-017-4450-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Accepted: 01/10/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Long-term outcome and natural history of steroid response in adult ulcerative colitis patients based on short-term response is largely unknown. AIM To evaluate whether short-term clinical response at 30 days after steroid initiation for moderate to severe disease can predict long-term outcome. METHODS This prospective observational study recruited 161 patients who received oral/intravenous steroid therapy at our institution from April 2005 to July 2009. Short-term response at 30 days and long-term response at the end of first and third years were measured. Risk factors for long-term outcome at 1 and 3 years were analyzed by multivariate regression model. RESULTS At the end of 30 days, 90 patients (55.9%) had complete response, 47 (29.2%) partial response, and 24 (14.9%) did not respond at all. At the end of first year, 53/90 (60%) complete responders (at 30 days) maintained steroid-free remission when compared to 17/71 (23.9%, p < 0.001) partial/no responders. Similar result was observed at the end of third year (74.7 vs 55.1%, p = 0.017). On multivariable analysis, short-term outcome at 30 days was a predictor of outcome at the end of one year (RR 4.1, 95% CI 2.2-8.5) and 3 years (RR 2.1, 95% CI 1.02-4.5). CONCLUSIONS Short-term response to steroids is a strong predictor of long-term outcome at 1 and 3 years in active ulcerative colitis patients.
Collapse
Affiliation(s)
- Tarun Rai
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Room No. 3111, Third Floor, Teaching Block, New Delhi, 110029, India
| | - Bikash Narayan Choudhury
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Room No. 3111, Third Floor, Teaching Block, New Delhi, 110029, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Room No. 3111, Third Floor, Teaching Block, New Delhi, 110029, India
| | - Sawan Bopanna
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Room No. 3111, Third Floor, Teaching Block, New Delhi, 110029, India
| | - Pratap Mouli Venigalla
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Room No. 3111, Third Floor, Teaching Block, New Delhi, 110029, India
| | - Sushil Kumar Garg
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Room No. 3111, Third Floor, Teaching Block, New Delhi, 110029, India
| | - Vikas Singla
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Room No. 3111, Third Floor, Teaching Block, New Delhi, 110029, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Room No. 3111, Third Floor, Teaching Block, New Delhi, 110029, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Room No. 3111, Third Floor, Teaching Block, New Delhi, 110029, India.
| |
Collapse
|
|
26
|
Khan N, Patel D, Shah Y, Yang YX. Factors Predicting Testing and Treatment of Iron Deficiency in a Nationwide Cohort of Anemic UC Patients. Inflamm Bowel Dis 2016; 22:2894-2901. [PMID: 27763952 DOI: 10.1097/mib.0000000000000947] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Iron deficiency anemia (IDA) is an often unrecognized and undertreated complication of ulcerative colitis (UC). We conducted the first nationwide study in the United States to evaluate the prevalence of testing for iron deficiency (ID) in anemic UC patients and determine the frequency of treatment with iron supplementation in patients with IDA. METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified. Primary outcome was to evaluate if anemic UC patients were tested for ID and subsequently treated with iron replacement therapy if IDA is confirmed. Candidate parameters included factors that can impact testing and treatment of anemia including patients' demographics, severity of anemia, and endoscopic findings. RESULTS Of 836 newly diagnosed patients with UC, 585 patients (70%) developed anemia over the course of median 8 years of follow-up. Of 585 patients, 401 patients (68.6%) had iron study evaluation. Two hundred fifty-one patients (62.6%) were diagnosed with IDA, and among them, 191 patients (76.1%) were treated with oral iron therapy. None of the patient received intravenous iron therapy. In multivariate analysis, patients with mild/moderate anemia and patients from Midwest and South region were independent predictors of iron study evaluation in patients with anemia. CONCLUSIONS More than a third of anemic UC patients were not tested for ID. Once tested, almost a quarter of the patients with IDA were not treated with iron replacement therapy. Testing for ID and subsequent treatment with iron replacement therapy should be considered among the quality process indicators in UC.
Collapse
Affiliation(s)
- Nabeel Khan
- *Section of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; †Section of Gastroenterology, VA Medical Center, Philadelphia, Pennsylvania; and ‡Department of Internal Medicine, Mercy Catholic Medical Center, Darby, Pennsylvania
| | | | | | | |
Collapse
|
|
27
|
Abstract
Ulcerative colitis (UC) is a chronic inflammatory condition that is variable in both extent and severity of disease as well as response to therapy. Corticosteroids (CSs) were the first drugs used in the management of UC and are still used for induction of remission. However, because of their extensive side-effect profile, they are not utilized for maintenance of remission. In view of this, CS-free remission has become an important end point while evaluating therapeutic agents used in the management of UC. This review highlights the results of various studies conducted to evaluate the efficacy of different medications to attain CS-free remission in the setting of active UC. The drugs reviewed include established agents such as thiopurines, methotrexate, infliximab, adalimumab, vedolizumab, golimumab, and newer experimental agents, and if all else fails, colectomy will be performed. The efficacy of these drugs is evaluated individually. Our aim is to provide a synopsis of the work done in this field to date.
Collapse
Affiliation(s)
- Hafiz M Waqas Khan
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Faisal Mehmood
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Nabeel Khan
- Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia VA Medical Center, Philadelphia, PA, USA
| |
Collapse
|
|
28
|
Khan NH, Almukhtar RM. Editorial: Early corticosteroids in ulcerative colitis--authors' reply. Aliment Pharmacol Ther 2014; 40:728. [PMID: 25123385 DOI: 10.1111/apt.12898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- N H Khan
- Department of Internal Medicine, Section of Gastroenterology, Southeast Louisiana Veterans Health Care System, New Orleans, LA, USA; Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia VA Medical Center, Philadelphia, PA, USA.
| | | |
Collapse
|
|
29
|
Affiliation(s)
- N A Kennedy
- Gastrointestinal Unit, Western General Hospital, Edinburgh, EH4 2XU, UK
| | | |
Collapse
|
|
30
|
Khan NH, Almukhtar RM, Cole EB, Abbas AM. Early corticosteroids requirement after the diagnosis of ulcerative colitis diagnosis can predict a more severe long-term course of the disease - a nationwide study of 1035 patients. Aliment Pharmacol Ther 2014; 40:374-81. [PMID: 24961751 DOI: 10.1111/apt.12834] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Revised: 07/15/2013] [Accepted: 05/22/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND There are limited data regarding clinical outcomes in ulcerative colitis (UC) patients who require early corticosteroids (CS) use. AIM To evaluate the rate of early CS utilisation (within 30 days of diagnosis) as a predictive marker for long-term outcomes, colectomy and CS dependency, in a population-based cohort of incident UC cases. METHODS Nationwide data were obtained from the Veterans Affairs (VA) health care system for the period 2001-2011. Incident UC cases were identified. A retrospective cohort design and time-to-event survival analysis were used to track outcomes of interest. Cox regression multivariate analysis was employed. RESULTS One thousand and thirty-five newly diagnosed patients with UC were identified and included in the analysis; 236 (23%) of those patients required early CS therapy. Patients were followed-up over a median time of 4.7 years (IQR 2.8-6.8) after UC diagnosis. The 5-year cumulative probability of requiring colectomy varied significantly by early CS use status (13% among early CS users compared to 4% among those who did not require early CS treatment, P < 0.001). Similar variation in the 5-year cumulative probability of CS dependency by early CS status was observed. Early CS users were more likely to require colectomy 2.9 (CI 1.7-5.0, P < 0.001) and to become CS dependent 4.5 (95% CI 3.6-5.7, P < 0.001) than non-users. CONCLUSIONS Early CS use can help identify those patients who have a more active disease course of UC. Recognising this can be among the indicators that can help physicians identify patients who may require early initiation of more aggressive therapy.
Collapse
Affiliation(s)
- N H Khan
- Department of Internal Medicine, Section of Gastroenterology, Southeast Louisiana Veterans Health Care System, New Orleans, LA, USA; Department of Internal Medicine, Section of Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, LA, USA
| | | | | | | |
Collapse
|
|
31
|
Abstract
This review describes the history of U.S. government funding for surveillance programs in inflammatory bowel diseases (IBD), provides current estimates of the incidence and prevalence of IBD in the United States, and enumerates a number of challenges faced by current and future IBD surveillance programs. A rationale for expanding the focus of IBD surveillance beyond counts of incidence and prevalence, to provide a greater understanding of the burden of IBD, disease etiology, and pathogenesis, is provided. Lessons learned from other countries are summarized, in addition to potential resources that may be used to optimize a new form of IBD surveillance in the United States. A consensus recommendation on the goals and available resources for a new model for disease surveillance are provided. This new model should focus on "surveillance of the burden of disease," including (1) natural history of disease and (2) outcomes and complications of the disease and/or treatments.
Collapse
|