|
1
|
Centanni L, Cicerone C, Fanizzi F, D’Amico F, Furfaro F, Zilli A, Parigi TL, Peyrin-Biroulet L, Danese S, Allocca M. Advancing Therapeutic Targets in IBD: Emerging Goals and Precision Medicine Approaches. Pharmaceuticals (Basel) 2025; 18:78. [PMID: 39861141 PMCID: PMC11768140 DOI: 10.3390/ph18010078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 01/04/2025] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) are chronic, relapsing conditions characterized by dysregulated immune responses and persistent intestinal inflammation. This review aims to examine new potential therapeutic targets in IBD starting from the STRIDE-II statements. Key targets now include clinical remission, endoscopic remission, and biomarker normalization (such as C-reactive protein and fecal calprotectin). Moreover, histologic remission, transmural remission, and in the future molecular targets are emerging as important indicators of sustained disease control. The treatment goals for inflammatory bowel disease are varied: to relieve symptoms, prevent permanent intestinal damage, promote inflammation remission, and minimize complications. Consequently, the therapeutic targets have evolved to become broader and more ambitious. Integrating these advanced therapeutic targets has the potential to redefine IBD management by promoting deeper disease control and improved patient outcomes. Further research is essential to validate these strategies and optimize their clinical implementation.
Collapse
Affiliation(s)
- Lucia Centanni
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele, University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Clelia Cicerone
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele, University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Fabrizio Fanizzi
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele, University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Ferdinando D’Amico
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele, University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Federica Furfaro
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele, University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele, University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Tommaso Lorenzo Parigi
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele, University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, INFINY Institute, INSERM NGERE, CHRU de Nancy, Université de Lorraine, F-54500 Vandœuvre-lès-Nancy, France
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele, University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Mariangela Allocca
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele, University Vita-Salute San Raffaele, 20132 Milan, Italy
| |
Collapse
|
|
2
|
Tursi A, Mocci G, Del Gaudio A, Papa A. Clinical use of biologics for Crohn's disease in adults: lessons learned from real-world studies. Expert Opin Biol Ther 2024:1-19. [PMID: 38321868 DOI: 10.1080/14712598.2024.2316180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 02/05/2024] [Indexed: 02/08/2024]
Abstract
INTRODUCTION The therapeutic armamentarium for managing Crohn's disease (CD) has expanded significantly in recent decades. Several biologics with three different mechanisms of action [anti-tumor necrosis factor (TNF)-α, anti-integrin α4β7, and anti-IL 12/23] are currently available to manage CD. AREA COVERED This narrative review aims to summarize the most significant efficacy and safety data on the use of infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ) and ustekinumab (UST) for the treatment of CD obtained from studies conducted in the real world (RW), compared to the results of randomized clinical trials (RCTs). EXPERT OPINION RW studies reported that biologic agents included in this analysis have higher remission rates and lower adverse event rates than findings from RCTs for treating patients with CD. All biological agents have proven effective and safe in RW studies, even when using biosimilars or switching to subcutaneous administration of the molecules for which they are available. Finally, anti-TNF-α agents, particularly IFX, have a higher rate of adverse events (AEs) than VDZ and UST. Therefore, patients at higher risk of AEs may benefit from other biologics than anti-TNF-α. However, further long-term RW studies are needed to confirm these findings.
Collapse
Affiliation(s)
- Antonio Tursi
- Territorial Gastroenterology Service, ASL BAT, Andria, Italy
- Department of Medical and Surgical Sciences, Catholic University, School of Medicine, Rome, Italy
| | - Giammarco Mocci
- Division of Gastroenterology, "Brotzu" Hospital, Cagliari, Italy
| | - Angelo Del Gaudio
- Division of Internal Medicine and Gastroenterology, Policlinico Universitario "A. Gemelli" IRCCS Foundation, Rome, Italy
| | - Alfredo Papa
- Department of Medical and Surgical Sciences, Catholic University, School of Medicine, Rome, Italy
- Division of Internal Medicine and Gastroenterology, Policlinico Universitario "A. Gemelli" IRCCS Foundation, Rome, Italy
| |
Collapse
|
|
3
|
Herrlinger KR, Stange EF. To STRIDE or not to STRIDE: a critique of "treat to target" in Crohn´s disease. Expert Rev Gastroenterol Hepatol 2023; 17:1205-1219. [PMID: 38131269 DOI: 10.1080/17474124.2023.2296564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 12/14/2023] [Indexed: 12/23/2023]
Abstract
INTRODUCTION The STRIDE consensus suggested to focus on mucosal healing, based on biomarkers and endoscopy, in addition to clinical endpoints as treatment target. This narrative review provides a critique of this concept in Crohn´s disease. AREAS COVERED We analyze and discuss the limitations of endpoints as targets, their currently limited achievability, and the controversial evidence relating to 'treat to target.' The relevant publications in Pubmed were identified in a literature review with the key word 'Crohn´s disease.' EXPERT OPINION All targets and endpoints have their limitations, and, even if reached, not all have unequivocally been shown to improve prognosis. The major deficiency of STRIDE is not only the lack of validation and agreement upon endpoints but little evidence of their achievability in a sizable proportion of patients by dose or timing adjustments or switching the medication. Above all, the concept should be based on clear evidence that patients indeed benefit from appropriate escalation of treatment and relevant controlled studies in this regard have been controversial. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant and expect more convincing evidence before new targets are approved.
Collapse
Affiliation(s)
| | - Eduard F Stange
- Innere Medizin I, UniversitätsklinikTübingen, Tübingen, Germany
| |
Collapse
|
|
4
|
Karami H, Shirvani Shiri M, Ebadi Fard Azar F, Bagheri Lankarani K, Ghahramani S, Rezapour A, Tatari M, Heidari Javargi Z. Factors associated with health-related quality of life in patients with Crohn's disease in Iran: A prospective observational study. Front Med (Lausanne) 2023; 9:1091330. [PMID: 36760884 PMCID: PMC9907090 DOI: 10.3389/fmed.2022.1091330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 12/30/2022] [Indexed: 01/20/2023] Open
Abstract
This was a 1-year prospective observational study of the health-related quality of life (HRQoL) of moderate to severe crohn's disease (CD) patients in Iran. Patients' HRQoL were measured using the EQ-5D 3L, EQ-VAS, and IBDQ-9 tools. HRQoL among CD patients were compared using the T-test, Mann-Whitney, Chi-square, and Fisher's exact tests. To discover factors influencing patients' HRQoL, multivariate linear regression and multivariate logistic regression tests were utilized. The study included 222 CD patients, with a mean age of 34.67 and mean disease duration of 7.32 years. The dimensions with the worst reported "relatively or extreme problems" were P/D: 77.5% and A/D: 63.1%. Employment, having "other chronic diseases," and ADA consumption were the most important independent predictors of HRQoL in CD patients, [β = 0.21 (EQ-5D index), β = 19.61 (EQ-VAS), β = 12.26 (IBDQ-9), OR: 0.09 (MO), OR: 0.12 (UA), OR: 0.21 (P/D), OR: 0.22 (A/D)], [β = -0.15 (EQ-5D index), β = -5.84 (IBDQ-9), β = -11.06 (EQ-VAS), OR: 4.20 (MO), OR: 6.50 (UA)], and [OR: 2.29 (A/D)], respectively. Unemployment, presence of "other chronic conditions" had the greatest negative impact on HRQoL of CD patients. There were significant differences in the probability of reporting "relatively or extreme problems" in the SC and A/D dimensions between patients using adalimumab (ADA) and infliximab (IFX).
Collapse
Affiliation(s)
- Hassan Karami
- Department of Economics, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Shirvani Shiri
- Department of Health Management and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Farbod Ebadi Fard Azar
- Health Promotion Research Center, Iran University of Medical Sciences, Tehran, Iran,*Correspondence: Farbod Ebadi Fard Azar ✉
| | - Kamran Bagheri Lankarani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Fars, Iran
| | - Sulmaz Ghahramani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Fars, Iran
| | - Aziz Rezapour
- Health Management and Economics Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Tatari
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran,Vice Chancellery of Health, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
| | - Zahra Heidari Javargi
- Department of Clinical Medicine, School of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| |
Collapse
|
|
5
|
Yang HH, Huang Y, Zhou XC, Wang RN. Efficacy and safety of adalimumab in comparison to infliximab for Crohn's disease: A systematic review and meta-analysis. World J Clin Cases 2022; 10:6091-6104. [PMID: 35949827 PMCID: PMC9254215 DOI: 10.12998/wjcc.v10.i18.6091] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 02/14/2022] [Accepted: 04/30/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Adalimumab (ADA) and infliximab (IFX) are the cornerstones of the treatment of Crohn’s disease (CD). It remains controversial whether there is a difference in the effectiveness and safety between IFX and ADA for CD.
AIM To perform a meta-analysis to compare the effectiveness and safety of ADA and IFX in CD.
METHODS PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Cohort studies were considered for inclusion. The primary outcomes were induction of response and remission, maintenance of response and remission, and secondary loss of response. Adverse events were secondary outcomes.
RESULTS Fourteen cohort studies were included. There was no apparent difference between the two agents in the induction response [odds ratio (OR): 1.27, 95% confidence interval (CI): 0.93-1.74, P = 0.14] and remission (OR: 1.11, 95%CI: 0.78–1.57, P = 0.57), maintenance response (OR: 1.08, 95%CI: 0.76–1.53, P = 0.67) and remission (OR: 1.26, 95%CI: 0.87–1.82, P = 0.22), and secondary loss of response (OR: 1.01, 95%CI: 0.65–1.55, P = 0.97). Subgroup analysis revealed ADA and IFX had similar rates of response, remission, and loss of response either in anti-tumor necrosis factor-α naïve or non-naïve patients. Further, there was a similar result regardless of whether CD patients were treated with optimized therapy, including dose intensification, shortening interval, and combination immunomodulators. However, ADA had a fewer overall adverse events than IFX (OR: 0.62, 95%CI: 0.42–0.91, P = 0.02).
CONCLUSION ADA and IFX have similar clinical benefits for anti-tumor necrosis factor-α naïve or non-naïve CD patients. Overall adverse events rate is higher in patients in the IFX group.
Collapse
Affiliation(s)
- Hua-Hua Yang
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yi Huang
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Xu-Chun Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Ruo-Nan Wang
- Department of Endocrinology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, Hubei Province, China
| |
Collapse
|
|
6
|
Bronsky J, Copova I, Kazeka D, Lerchova T, Mitrova K, Pospisilova K, Sulovcova M, Zarubova K, Hradsky O. Adalimumab vs Infliximab in Pediatric Patients With Crohn's Disease: A Propensity Score Analysis and Predictors of Treatment Escalation. Clin Transl Gastroenterol 2022; 13:e00490. [PMID: 35363628 PMCID: PMC9132518 DOI: 10.14309/ctg.0000000000000490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 03/04/2022] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Two antitumor necrosis factor therapies (infliximab [IFX] and adalimumab [ADA]) have been approved for the treatment of pediatric Crohn's disease (CD) but have not been compared in head-to-head trials. The aim of this study was to compare the efficacy and safety of ADA and IFX by propensity score matching in a prospective cohort of pediatric patients with luminal CD and at least a 24-month follow-up. METHODS Among 100 patients, 75 met the inclusion criteria, and 62 were matched by propensity score. We evaluated time to treatment escalation as the primary outcome and primary nonresponse, predictors of treatment escalation and relapse, serious adverse events, pharmacokinetics, and effect of concomitant immunomodulators as secondary outcomes. RESULTS There was no difference between ADA and IFX in time to treatment escalation (HR = 0.63 [95% CI 0.31-1.28] P = 0.20), primary nonresponse (P = 0.95), or serious adverse events. The median (interquartile range) trough levels at the primary outcome were 14.05 (10.88-15.40) and 6.15 (2.08-6.58) µg/mL in the ADA and IFX groups, respectively. On a multivariate analysis, the combination of anti-Saccharomyces cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity was a strong independent predictor of treatment escalation (HR 5.19, [95% CI 2.41-11.18], P < 0.0001). The simple endoscopic score for CD, L3 disease phenotype, and use of concomitant immunomodulators for at least the first 6 months revealed a trend toward significance on a univariate analysis. DISCUSSION Propensity score matching did not reveal substantial differences in efficacy or safety between ADA and IFX. The anti-S. cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity combination is a strong predictor of treatment escalation.
Collapse
Affiliation(s)
- Jiri Bronsky
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Ivana Copova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Denis Kazeka
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Tereza Lerchova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Katarina Mitrova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
- IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic.
| | - Kristyna Pospisilova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Miroslava Sulovcova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Kristyna Zarubova
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| | - Ondrej Hradsky
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic;
| |
Collapse
|
|
7
|
Mosli M, Alameel T, Sharara AI. Mucosal Healing in Crohn's Disease: Bull's Eye or Bust? The "Relative" Con Position. Inflamm Intest Dis 2022; 7:42-49. [PMID: 35224017 PMCID: PMC8820152 DOI: 10.1159/000519731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 09/15/2021] [Indexed: 10/07/2023] Open
Abstract
BACKGROUND Crohn's disease is a progressive inflammatory bowel disease. Persistent untreated inflammation can cumulatively result in bowel damage in the form of strictures, fistulas, and fibrosis, which can ultimately result in the need for major abdominal surgery. Mucosal healing has emerged as an attractive, yet ambitious goal in the hope of preventing long-term complications. SUMMARY Clinical remission is an inadequate measure of disease activity. Noninvasive markers such as fecal calprotectin, CRP, or small bowel ultrasound are useful adjunct tools. However, endoscopic assessment remains the cornerstone in building a treatment plan. Achieving complete mucosal healing has proved to be an elusive goal even in the ideal setting of a clinical trial. KEY MESSAGES Aiming for complete mucosal healing in all patients may result in overuse of medications, higher costs, and potential side effects of aggressive immunosuppressive treatment. More practical goals such as relative or partial healing, for example, 50% improvement in inflammation and reduction in size of ulcers, ought to be considered, particularly in difficult-to-treat populations.
Collapse
Affiliation(s)
- Mahmoud Mosli
- Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Turki Alameel
- Department of Medicine, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Ala I. Sharara
- Division of Gastroenterology, Department of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| |
Collapse
|
|
8
|
Long-term real-life efficacy and safety of infliximab and adalimumab in the treatment of inflammatory bowel diseases outpatients. Eur J Gastroenterol Hepatol 2021; 33:670-679. [PMID: 33741797 DOI: 10.1097/meg.0000000000002087] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Infliximab and adalimumab are widely used for the treatment of Crohn's disease and ulcerative colitis. AIM To compare the long-term efficacy and safety of infliximab and adalimumab in a large cohort of Crohn's disease and ulcerative colitis patients reflecting real-life clinical practice. METHODS Seven hundred twelve patients were retrospectively reviewed, 410 with Crohn's disease (268 treated with adalimumab and 142 with infliximab; median follow-up 60 months, range, 36-72) and 302 with ulcerative colitis (118 treated with adalimumab and 184 with infliximab; median follow-up 48 months, range, 36-84). RESULTS In Crohn's disease, clinical remission was maintained in 75.0% of adalimumab vs. in 72.5% of infliximab patients (P = 0.699); mucosal healing and steroid-free remission were maintained in 49.5% of adalimumab vs. 63.9% of infliximab patients (P = 0.077) and in 77.7% of adalimumab vs. 77.3% in infliximab group (P = 0.957), respectively. In ulcerative colitis, clinical remission was maintained in 50.0% of adalimumab vs. 65.8% of infliximab patients (P < 0.000); mucosal healing and steroid-free remission were maintained in 80.6% of adalimumab vs. 77.0% of infliximab patients (P = 0.494) and in 90.2% of adalimumab vs. 87.5% of infliximab patients (P = 0.662), respectively. At the multivariate analysis, ileocolonic location and simple endoscopic score for Crohn's disease >10 were predictors of failure in Crohn's disease; treatment with adalimumab, BMI ≥30 and Mayo score >10 were predictors of failure in ulcerative colitis. infliximab was more likely to cause adverse events than adalimumab (16.6 vs. 6.2%, P < 0.000). CONCLUSION Both adalimumab and infliximab are effective in long-term outpatients management of inflammatory bowel diseases. Adalimumab had a lower rate of adverse events.
Collapse
|
|
9
|
Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, Bettenworth D, Sandborn WJ, Sands BE, Reinisch W, Schölmerich J, Bemelman W, Danese S, Mary JY, Rubin D, Colombel JF, Peyrin-Biroulet L, Dotan I, Abreu MT, Dignass A. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology 2021; 160:1570-1583. [PMID: 33359090 DOI: 10.1053/j.gastro.2020.12.031] [Citation(s) in RCA: 1492] [Impact Index Per Article: 373.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 10/21/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD. METHODS Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7 to 10 on a 10-point rating scale. RESULTS In the systematic review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed. STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life, and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in Crohn's disease and histological healing in ulcerative colitis are not formal targets but should be assessed as measures of the remission depth. CONCLUSIONS STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This frameworkshould be adapted to individual patients and local resources to improve outcomes.
Collapse
Affiliation(s)
- Dan Turner
- Shaare Zedek Medical Center, the Hebrew University of Jerusalem, Jerusalem, Israel.
| | | | - Ayanna Lewis
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Ferdinando D'Amico
- Humanitas Clinical and Research Center - IRCCS, Rozzano and Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan, Italy
| | - Jasbir Dhaliwal
- Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio
| | | | - Dominik Bettenworth
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Bruce E Sands
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Walter Reinisch
- Medical University of Vienna, Department of Internal Medicine III, Division Gastroenterology and Hepatology, Vienna, Austria
| | | | - Willem Bemelman
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Locatie AMC, the Netherlands
| | - Silvio Danese
- Humanitas Clinical and Research Center - IRCCS, Rozzano and Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan, Italy
| | - Jean Yves Mary
- Inserm UMR1153 CRESS, équipe ECSTRRA, Université de Paris, Paris, France
| | - David Rubin
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, Illinois
| | - Jean-Frederic Colombel
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Maria T Abreu
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt/Main, Germany.
| | | |
Collapse
|
|
10
|
Benmassaoud A, Al-Taweel T, Sasson MS, Moza D, Strohl M, Kopylov U, Paradis-Surprenant L, Almaimani M, Bitton A, Afif W, Lakatos PL, Bessissow T. Comparative Effectiveness of Infliximab Versus Adalimumab in Patients with Biologic-Naïve Crohn's Disease. Dig Dis Sci 2018; 63:1302-1310. [PMID: 29243105 DOI: 10.1007/s10620-017-4874-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Accepted: 11/29/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Direct head-to-head studies comparing the long-term outcomes of infliximab (IFX) to adalimumab (ADA) in Crohn's disease (CD) are sparse. AIMS We compared the short-term and long-term efficacy and safety of IFX and ADA in CD. METHODS We performed a single-center retrospective study including biologic-naïve adult patients with CD who were started on IFX or ADA at the McGill University Health Center. The primary end points were clinical response and remission at 12 months. Secondary end points included corticosteroid-free remission at 12 months, durable remission, and treatment failure with need for steroids, hospitalization or surgery. Safety was also assessed. RESULTS Two hundred and twenty patients were included (143 IFX, 77 ADA). Patients on IFX had a higher prevalence of fistulizing or perianal disease and corticosteroid treatment at baseline. Rates of clinical remission and corticosteroid-free remission at 12 months were similar between both groups: 63.8 versus 76.3% (p = 0.139) and 54.1 versus 44.7% (p = 0.354), respectively, for IFX and ADA. Combination therapy led to significantly higher remission rates at 12 months compared to monotherapy for patients on IFX (81.2 vs. 52.1%, p = 0.008), but not for those on ADA. Higher rates of adverse events were reported with IFX compared to ADA (p = 0.006). CONCLUSIONS Our real-life experience in biologic-naïve CD patients demonstrated that patients started on IFX were more likely to have a harder-to-treat phenotype. Despite that, efficacy end points were similar between both groups. Clinical remission was higher in patients with combination therapy for IFX, but not for those on ADA. This warrants further investigation.
Collapse
Affiliation(s)
- Amine Benmassaoud
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
| | - Talal Al-Taweel
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
- Haya Al-Habeeb Gastroenterology Center, Mubarak Al-Kabeer Hospital, Jabriya, Kuwait
| | - Mark Solomon Sasson
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
| | - Dasha Moza
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
| | - Matthew Strohl
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
| | - Uri Kopylov
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
- Department of Gastroenterology, Sheba Medical Centre, Tel-Aviv, Israel
| | - Laurence Paradis-Surprenant
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
| | - Mohanad Almaimani
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
| | - Alain Bitton
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
| | - Waqqas Afif
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
| | - Peter L Lakatos
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada
- First Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Talat Bessissow
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650, Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada.
| |
Collapse
|
|
11
|
Proposal for an anti-TNF-exit strategy based on trough serum level. Biologicals 2017; 47:81-85. [PMID: 28400083 DOI: 10.1016/j.biologicals.2017.03.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Revised: 02/04/2017] [Accepted: 03/08/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIMS The aim of the study was to evaluate, if the strategy to stop anti-TNF treatment after determination of low trough serum levels and exclusion of inflammation is associated with lower relapse rates. METHODS Since 2013 we followed an exit strategy in patients treated with anti-TNF treatment for inflammatory bowel disease based on trough serum levels. The relapse rates were observed prospectively, data analysis was performed in a retrospective manner of the collected clinical data. RESULTS Forty patients were enrolled, who stopped anti-TNF therapy. 13 Patients followed the clinical algorithm, 27 patients were used as control group (13 patients with ulcerative colitis and 14 patients with Crohn's disease). 19 patients received Infliximab, 21 Adalimumab. The median follow-up time after discontinuation was 19 months (IQR 18). Relapses were observed in 22/40 patients (55%). Among the 13 patients with a targeted discontinuation of therapy based on the algorithm, three relapses were observed (23%), compared to 19/27 (70%) from the non-algorithm group (OR: 7.9; 95%-CI: 1.7-36.5). Relapse-free-survival after anti-TNF discontinuation was significantly higher in patients treated by the algorithm compared to the non-algorithm group (p = 0.032). CONCLUSION An exit strategy based on trough serum levels significantly reduces the relapse rate.
Collapse
|
|
12
|
Srinivas NR. Letter: comparative safety and efficacy of infliximab vs. adalimumab in Crohn's disease - should one consider disease location? Aliment Pharmacol Ther 2016; 44:771-2. [PMID: 27593430 DOI: 10.1111/apt.13743] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- N R Srinivas
- Zydus Research Center, Ahmedabad, Gujarat, India.
| |
Collapse
|
|
13
|
Narula N, Kainz S, Petritsch W, Haas T, Feichtenschlager T, Novacek G, Eser A, Vogelsang H, Reinisch W, Papay P. The efficacy and safety of either infliximab or adalimumab in 362 patients with anti-TNF-α naïve Crohn's disease. Aliment Pharmacol Ther 2016; 44:170-80. [PMID: 27226407 DOI: 10.1111/apt.13671] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Revised: 11/23/2015] [Accepted: 04/29/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND TNFα antagonists, including infliximab (IFX) and adalimumab (ADA), have revolutionised treatment for Crohn's disease. Studies comparing efficacy in patients with Crohn's disease naïve to TNFα antagonists are lacking. METHODS Consecutive TNFα antagonist-naïve patients with luminal or perianal Crohn's disease from four tertiary centres in Austria were assessed prospectively for induction and maintenance efficacy, and safety, of either IFX or ADA. RESULTS In a total of 362 patients, 251 (69.3%) started IFX and 111 (30.7%) started ADA. At baseline, the median Harvey-Bradshaw Index (HBI) score was 8 (range 5-29) and 8 (5-36), and the median C-reactive protein (CRP) was 1.07 (interquartile range (IQR) 1.36) mg/dL and 1.16 (IQR 1.23) mg/dL for IFX and ADA, respectively. At week 12, there was no difference between IFX and ADA among patients with luminal Crohn's disease in clinical remission (IFX 128/204; 62.7% vs. ADA 68/107; 63.6%, P = 0.47), clinical response (IFX 154/204; 75.5% vs. ADA 82/107; 76.6%, P = 0.82) and steroid-free remission (IFX 110/204; 53.9% vs. ADA 61/107; 57%, P = 0.60). At 12 months, there were similar numbers of patients treated with IFX and ADA who maintained clinical remission (IFX 77/154; 50.4% vs. ADA 47/82; 57.3%, P = 0.48) and steroid-free remission (IFX 68/154; 44.3% vs. ADA 44/82; 53.7%, P = 0.16). Baseline CRP >0.7 mg/dL (OR 0.24; 95% CI 0.07-0.77, P = 0.01) was the only predictor of clinical remission at 12 months in patients who did not have escalation of anti-TNFα therapy. CONCLUSION IFX and ADA appear comparable in clinical outcomes for patients with Crohn's disease who are naïve to TNFα antagonists.
Collapse
Affiliation(s)
- N Narula
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - S Kainz
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - W Petritsch
- Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - T Haas
- Department of Internal Medicine 1, Paracelsus Private Medical University, Salzburg, Austria
| | - T Feichtenschlager
- Department of Internal Medicine 4, Hospital Rudolfstifung, Vienna, Austria
| | - G Novacek
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - A Eser
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - H Vogelsang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - W Reinisch
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.,Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - P Papay
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
14
|
Abstract
BACKGROUND The availability of monoclonal antibodies to tumor necrosis factor α has revolutionized management of Crohn's disease (CD) and ulcerative colitis. However, limited data exist regarding comparative effectiveness of these agents to inform clinical practice. METHODS This study consisted of patients with CD or ulcerative colitis initiation either infliximab (IFX) or adalimumab (ADA) between 1998 and 2010. A validated likelihood of nonresponse classification score using frequency of narrative mentions of relevant symptoms in the electronic health record was applied to assess comparative effectiveness at 1 year. Inflammatory bowel disease-related surgery, hospitalization, and use of steroids were determined during this period. RESULTS Our final cohort included 1060 new initiations of IFX (68% for CD) and 391 of ADA (79% for CD). In CD, the likelihood of nonresponse was higher in ADA than IFX (odds ratio, 1.62 and 95% CI, 1.21-2.17). Similar differences favoring efficacy of IFX were observed for the individual symptoms of diarrhea, pain, bleeding, and fatigue. However, there was no difference in inflammatory bowel disease-related surgery, hospitalizations, or prednisone use within 1 year after initiation of IFX or ADA in CD. There was no difference in narrative or codified outcomes between the 2 agents in ulcerative colitis. CONCLUSIONS We identified a modestly higher likelihood of symptomatic nonresponse at 1 year for ADA compared with IFX in patients with CD. However, there were no differences in inflammatory bowel disease-related surgery or hospitalizations, suggesting these treatments are broadly comparable in effectiveness in routine clinical practice.
Collapse
|
|
15
|
|
|
16
|
Tursi A. Histologic healing in inflammatory bowel disease clinical practice: a reliable target? Clin Gastroenterol Hepatol 2015; 13:1211-2. [PMID: 25066839 DOI: 10.1016/j.cgh.2014.07.031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 07/17/2014] [Accepted: 07/17/2014] [Indexed: 02/07/2023]
Affiliation(s)
- Antonio Tursi
- Servizio di Gastroenterologia Territoriale, Distretto Socio-Sanitario n°4, Azienda Sanitaria Locale Barletta-Andria-Trani, Andria, Italy
| |
Collapse
|
|
17
|
Chang CW, Wei SC, Chou JW, Hsu TC, Chuang CH, Lin CP, Hsu WH, Yen HH, Lin JK, Fang YJ, Wang HY, Lin HH, Wu DC, Ni YH, Wang CY, Wong JM. Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study. Intest Res 2014; 12:287-92. [PMID: 25374494 PMCID: PMC4214955 DOI: 10.5217/ir.2014.12.4.287] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Revised: 10/10/2014] [Accepted: 10/11/2014] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND/AIMS Only moderate to severe Crohn's Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria. METHODS A retrospective analysis was conducted in nine medical centers in Taiwan and we collected the results of CD patients receiving adalimumab from Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI (Crohn's Disease Activity Index), adverse events and survival status were recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI decrease of 70, 100 or 150 points compared with baseline. RESULTS A total of 103 CD patient records were used in this study. Sixty percent of these patients received combination therapy of adalimumab together with immunomodulators. CR-70 was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of patients, respectively. In considering the mucosal healing, only 25% patients achieve mucosal healing after treatment for 6 to 12 months. Surgery was still needed in 16.5% of patients. Combination treatment of adalimumab with immunomodulators further decreased the level of CDAI at week 8 when compared with the monotherapy. CONCLUSIONS Even under the stringent criteria for using adalimumab, the response rate was comparable to those without stringent criteria.
Collapse
Affiliation(s)
- Chen-Wang Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei; Mackay Junior College of Medicine, Nursing and Management, Taipei; Mackay Medical College, New Taipei, Taiwan
| | - Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Jen-Wei Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Tzu-Chi Hsu
- Division of Colon and Rectal Surgery, Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chiao-Hsiung Chuang
- Department of Internal Medicine, Medical College and Hospital, National Cheng-Kung University, Tainan, Taiwan
| | - Ching-Pin Lin
- Division of Gastroenterology, Chung Shan Medical University, Taichung, Taiwan
| | - Wen-Hung Hsu
- Department of Gastroenterology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsu-Heng Yen
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Jen-Kou Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei; Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yi-Jen Fang
- Division of Gastroenterology, Department of Medicine, Show Chwan Memorial Hospital, Changhuan, Taiwan
| | - Horng-Yuan Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei; Mackay Junior College of Medicine, Nursing and Management, Taipei; Mackay Medical College, New Taipei, Taiwan
| | - Hung-Hsin Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei; Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Deng Cheng Wu
- Department of Gastroenterology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yen Hsuan Ni
- Department of Pediatrics, National Taiwan University, Taipei, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Jau-Min Wong
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| |
Collapse
|