Effectiveness of third-class biologic treatment in crohn’s disease : A multi-center retrospective cohort study

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti-Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second-and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second-and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.Peer reviewe

Is there a correlation between infliximab trough levels and the development of adverse events in patients with inflammatory bowel disease?

Background/Aims: The measurement of infliximab trough levels (IFX-TLs) in patients with inflammatory bowel disease (IBD) is performed to optimize treatment. However, the association between the development of adverse events (AEs) and IFX-TLs has not been sufficiently studied thus far. To investigate the possible association of IFX-TLs with AEs in Greek patients with IBD receiving maintenance treatment with IFX Methods: A retrospective analysis of the registry data of the Gastroenterology Department of the University Hospital of Heraklion, from IBD patients with at least one available IFX-TL measurement during the years 2016 to 2017 was conducted. AEs reported 4 months before and 4 months after the measured IFX-TLs were recorded. The IFX-TLs of patients with or without AEs were compared. Results: Of a total of 83 IBD patients (61 Crohn’s disease [73%]; 52 men [63%]; mean age ± standard deviation, 43.3 ± 16.0 years), 147 measurements of IFX-TLs were available (median 4.69 µg/ mL [1.32–9.16]), and 99 AEs (67.3%, 14 severe) were registered. The median IFX-TL of patients with AEs was 5.79 µg/mL (1.36–10.25), higher than the median IFX-TL of patients without AEs (3.40 µg/mL [1.30–5.92]), but the difference was not significant (P = 0.97). The presence of infections or dermatologic reactions was not correlated with IFX-TLs. There was no difference in the prevalence of the total AEs (66.7% vs. 73.3%, P =0.77) or in the analysis of AEs by group between patients with IFX-TLs ≥ 15 µg/ mL and patients with IFX-TLs < 15 µg/mL. Conclusions: IFX-TLs are not significantly associated with the development of AEs in IBD patients receiving maintenance treatment with IFX. (Intest Res 2021;19:461–467) © 2021. Korean Association for the Study of Intestinal Diseases

Analysis of Clinical Trial Screen Failures in IBD: Real World Results from the IOIBD

peer reviewedBackground: Recruitment rates for phase 2b/3 randomized controlled trials (RCTs) in IBD have substantially dropped over time. Several steps are required prior to successful patient randomization. Initially the physician must propose a trial to a potentially eligible patient during a pre-screening process (step 1). This is followed by patient’s acceptance or refusal (step 2). Finally, after informed consent the patient undergoes trial screening to ensure they meet all eligibility criteria (step 3). Evaluating each step separately, this study aims to assess reasons why IBD patients are not included in RCT and patients’ outcome after screen failure (SF). Methods: All IOIBD member physicians (n=58) were invited to participate. To assess steps 1 and 2, consecutive IBD patients in relapse for whom a treatment change was required were prospectively included over a 4-week period. Reasons that prevented the IBD physician offering a sponsored multicenter phase 2b/3 RCT (step 1) and reasons why the patient accepted or refused to participate (step 2) were assessed through a physician and a patient survey, respectively. Reasons for SF (step 3) from the last 6 months, including the 4 weeks of steps 1-2, were collected retrospectively. Results: A total of 104 (59 male, 62 CD, mean age of 37.2 years) and 102 patients (58 male, 63 CD, mean age of 40.6 years) from 12 centers were included in steps 1-2 and 3, respectively (Tables 1 and 2). Among 104 patients in relapse for whom a treatment change was required, 41 (39.4%) were offered a RCT. Of the 28 who consented to RCT, 5 failed their screening (SF rate of 17.9%) and 23 were included. Main reason that prevent IBD physicians from offering an RCT (step 1) are shown in Figure 1. After receiving information about RCT, major reasons why patients accepted or refused to participate included the trust they had in their IBD specialist and the risk of being assigned to a placebo, respectively (step 2). Regarding 102 patients included in step 3, main reasons of SF were insufficient disease activity (n=37), concurrent infection (n=15) and dropout (n=12) (Figure 2). Half of SFs could have been avoided by thorough prescreening. After SF, 51 patients were treated with commercially available therapy, 14 were rescreened for the same RCT (after resolution of the issue leading to SF), no treatment was required for 14, 10 were referred to surgery and 6 were screened for another RCT (the outcome was unknown for 7). Conclusion: This first multicentric study reported a SF rate of 17.9%. Insufficient disease activity and the risk of assigning the patient to a placebo seem to be barriers to inclusion. Half of SFs could have been avoided by better pre-screening. After SF, most of patients were treated with commercially available therapy

Analysis of Clinical Trial Screen Failures in IBD: Real World Results from the IOIBD

peer reviewedBackground: Recruitment rates for phase 2b/3 randomized controlled trials (RCTs) in IBD have substantially dropped over time. Several steps are required prior to successful patient randomization. Initially the physician must propose a trial to a potentially eligible patient during a pre-screening process (step 1). This is followed by patient’s acceptance or refusal (step 2). Finally, after informed consent the patient undergoes trial screening to ensure they meet all eligibility criteria (step 3). Evaluating each step separately, this study aims to assess reasons why IBD patients are not included in RCT and patients’ outcome after screen failure (SF). Methods: All IOIBD member physicians (n=58) were invited to participate. To assess steps 1 and 2, consecutive IBD patients in relapse for whom a treatment change was required were prospectively included over a 4-week period. Reasons that prevented the IBD physician offering a sponsored multicenter phase 2b/3 RCT (step 1) and reasons why the patient accepted or refused to participate (step 2) were assessed through a physician and a patient survey, respectively. Reasons for SF (step 3) from the last 6 months, including the 4 weeks of steps 1-2, were collected retrospectively. Results: A total of 104 (59 male, 62 CD, mean age of 37.2 years) and 102 patients (58 male, 63 CD, mean age of 40.6 years) from 12 centers were included in steps 1-2 and 3, respectively (Tables 1 and 2). Among 104 patients in relapse for whom a treatment change was required, 41 (39.4%) were offered a RCT. Of the 28 who consented to RCT, 5 failed their screening (SF rate of 17.9%) and 23 were included. Main reason that prevent IBD physicians from offering an RCT (step 1) are shown in Figure 1. After receiving information about RCT, major reasons why patients accepted or refused to participate included the trust they had in their IBD specialist and the risk of being assigned to a placebo, respectively (step 2). Regarding 102 patients included in step 3, main reasons of SF were insufficient disease activity (n=37), concurrent infection (n=15) and dropout (n=12) (Figure 2). Half of SFs could have been avoided by thorough prescreening. After SF, 51 patients were treated with commercially available therapy, 14 were rescreened for the same RCT (after resolution of the issue leading to SF), no treatment was required for 14, 10 were referred to surgery and 6 were screened for another RCT (the outcome was unknown for 7). Conclusion: This first multicentric study reported a SF rate of 17.9%. Insufficient disease activity and the risk of assigning the patient to a placebo seem to be barriers to inclusion. Half of SFs could have been avoided by better pre-screening. After SF, most of patients were treated with commercially available therapy

Analysis of Clinical Trial Screen Failures in Inflammatory Bowel Diseases (IBD): Real World Results from the International Organization for the study of IBD

Abstract Background Recruitment for randomized controlled trials (RCTs) in IBD have substantially dropped over time. This study aimed to assess reasons why IBD patients are not included in sponsored multicenter phase IIb-III RCTs. Methods All IOIBD members (n=58) were invited to participate. We divided barriers to participation as follow: 1) reasons patients with active IBD were not deemed appropriate for a RCT; 2) reasons qualified patients did not wish to participate; 3) reasons for screen failure (SF) in patients agreeing to participate. We assess those in a 4-week prospective study including, consecutively, all patients with symptomatic disease for whom a treatment change was required. In addition, we performed a 6-month retrospective study to further evaluate reasons for SF. Results A total of 106 patients (60 male (56.6%), 63 Crohn’s disease [CD] (59.4%)), from 10 centers across the world, were included in the prospective study. A RCT has not been proposed to 65 of them (mainly due to eligibility criteria). Of the 41 patients to whom a RCT was offered, 8 refused (mainly due to reluctance to receive placebo) and 28 agreed to participate. Among these 28 patients, 5 failed their screening and 23 were finally included in a RCT. A total of 107 patients (61 male (57%), 67 CD (62.6%)), from 13 centers worldwide, were included in our retrospective study of SFs. The main reason was insufficient disease activity. Conclusion This first multicenter study analyzing reasons for non-enrollment in IBD RCTs shown that we lose patients at each step. Eligibility criteria, the risk of placebo assignment and insufficient disease activity were part of the main barriers

Effectiveness of third-class biologic treatment in crohn\u2019s disease: A multi-center retrospective cohort study

Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn\u2019s disease (CD) failing anti-Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second-and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second-and VDZ as a third-class therapy (group B). At week 16\u201322, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent

Gastroenteropancreatic Neuroendocrine Neoplasms in Patients with Inflammatory Bowel Disease: An ECCO CONFER Multicentre Case Series

Background: Gastroenteropancreatic neuroendocrine neoplasms [GEP-NENs] have rarely been reported in association with inflammatory bowel diseases [IBDs]. Methods: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collects cases of GEP-NENs diagnosed in patients with IBD. Results: GEP-NEN was diagnosed in 100 IBD patients; 61% female, 55% Crohn's disease, median age 48 years (interquartile range [IQR] 38-59]). The most common location was the appendix [39%] followed by the colon [22%]. Comprehensive IBD-related data were available for 50 individuals with a median follow-up of 30 months [IQR 11-70] following NEN diagnosis. Median duration of IBD at NEN diagnosis was 84 months [IQR 10-151], and in 18% of cases NEN and IBD were diagnosed concomitantly. At diagnosis, 20/50 were stage-I [T1N0M0], and 28/50 were graded G1 [ki67 ≤2%]. Incidental diagnosis of NEN and concomitantly IBD diagnosis were associated with an earlier NEN stage [p = 0.01 and p = 0.02, respectively]. Exposure to immunomodulatory or biologic therapy was not associated with advanced NEN stage or grade. Primary GEP-NEN were more frequently found in the segment affected by IBD [62% vs 38%]. At the last follow-up data, 47/50 patients were alive, and only two deaths were related to NEN. Conclusions: In the largest case series to date, prognosis of patients with GEP-NEN and IBD seems favourable. Incidental NEN diagnosis correlates with an earlier NEN stage, and IBD-related therapies are probably independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis