Al‐Bawardy, Badr

Importance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135

Abstract Background Since 2009, inflammatory bowel disease (IBD) specialists have utilized “IBD LIVE,” a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified “IBD-mimics” with consequent clinical management implications. Methods Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018–February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup. Results Confirmed IBD cases made up 82.5% (306/371; 193 Crohn’s disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced (n = 8) or vasculitis (n = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies (n = 13, 21%), surgical exploration/pathology (n = 10, 16.5%), biopsies from outside the GI tract (n = 10, 16.5%), genetic/laboratory testing (n = 8, 13%), extensive review of patient history (n = 8, 13%), imaging (n = 5, 8%), balloon enteroscopy (n = 5, 8%), and capsule endoscopy (n = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib. Conclusions The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care.

Abstract Background Inflammatory bowel disease (IBD) treatment targets include mucosal healing based on standardized endoscopic scoring systems. The rates and ease of use of these scoring systems in practice have not been well described. We aimed to assess the rates and factors associated with the use of IBD endoscopic scoring systems in practice from IBD LIVE attendees. Methods IBD Live is an international case-based conference focusing on the management of patients with IBD. We created a web-based survey consisting of 38 questions on the frequency and ease of use of various IBD endoscopic scores. This survey was emailed to the IBD Live listserv in March 2022 with a second email sent 14 days later. We included only respondents who are currently performing endoscopy. Continuous variables were analyzed using an unpaired student’s t-test. Categorical variables were analyzed using Pearson’s chi-square test. Results There were 65 responses out of 170 (38.2% response rate) regular attendees. Eleven responses were excluded (4 with no response on the use of endoscopy scores, and 7 were not performing endoscopy). Of the respondents, 72.2% are from the United States, 70.4% are adult gastroenterologists, 53.9% in academic practice, and 40.7% in practice for ≥15 years. Of the endoscopy scores used ≥50% of the time, 74.1% were using the Mayo Endoscopic Subscore (MES), 72.3% using the Rutgeerts Score, 61.2% using the Simple Endoscopic Score for Crohn’s Disease, and 28.6% using the Pouchitis Disease Activity Index. Attending IBD LIVE ≥ monthly (P = .028), attending an IBD conference at least every 2 years (P = .020), and having the scoring system incorporated into the endoscopy documentation software (P = .002) were associated with more consistent use of the MES. Attending IBD Live at least monthly (P = .026), having an IBD volume of ≥50% (P = .011), and attending an IBD conference at least every 2 years (P = .004) was associated with more frequent use of the Rutgeerts score. There were no factors that increased the use of other endoscopic scores. Conclusions The MES and the Rutgeerts score are more commonly used with much lower rates of use of endoscopic scores for Crohn’s disease and pouchitis. The use of these endoscopy scores is more common among those who regularly attend IBD conferences, have higher volume IBD practices, and have these scoring systems incorporated into endoscopy software. Further evaluation of barriers to use and ways to improve utilization of endoscopic scoring for Crohn’s disease and pouchitis is needed.

Abstract Background Certolizumab pegol (CZP) has been successfully used for the treatment of Crohn disease (CD); however, real-world data regarding the utility of CZP trough levels (CTLs) are lacking. We aimed to correlate CTL with CD outcomes and to determine frequency of CZP antibodies. Methods Retrospective evaluation of all CD patients on maintenance CZP with CTL obtained between 2016 and 2019. Outcomes included: median CTL, presence of anti-CZP antibodies, biochemical response (BR), clinical response (CR), radiologic response (RR), radiologic healing (RH), and mucosal healing (MH). Results Seventy-seven CD patients were included. Median CTL was 18.9 µg/mL (interquartile range, 7.6–35.4). Twenty-three patients (27.3%) had positive antibody levels, with lower median CTL compared to patients with no antibodies (0.0 vs 29.8; P < 0.0001). Median CTL levels were higher in patients with vs without CR (30.4 vs 10.3 µg/mL; P = 0.0015) and RR (29.6 vs 5.8 µg/mL; P = 0.006). CZP dosing at least every 2 weeks was associated with higher odds of achieving MH (odds ratio, 3.2; 95% confidence interval, 1.03–9.97). CTL resulted in change in clinical management in 62.7% of cases and presence of CMZ antibodies was associated with an odds ratio of 5.83 (95% confidence interval, 1.57–21.73) of change in management. Receiver operating characteristic curve and quartile analysis suggested that CTL >19 µg/mL is associated with increased rates of CR and RR. Conclusions Higher CTL was significantly associated with CR and RR. The rate of CZP antibodies was 27.3%. Our data suggest maintenance CTL of ≥19 µg/mL should be achieved in order to optimize outcomes in clinical practice.

Abstract Background There are limited data on how vedolizumab (VDZ) impacts extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD). The aim of this study was to determine the clinical outcomes of EIMs after initiation of VDZ for patients with IBD. Methods A multicenter retrospective study of patients with IBD who received at least 1 dose of VDZ between January 1, 2014 and August 1, 2019 was conducted. The primary outcome was the rate of worsening EIMs after VDZ. Secondary outcomes were factors associated with worsening EIMs and peripheral arthritis (PA) specifically after VDZ. Results A total of 201 patients with IBD (72.6% with Crohn disease; median age 38.4 years (interquartile range, 29-52.4 years); 62.2% female) with EIMs before VDZ treatment were included. The most common type of EIM before VDZ was peripheral arthritis (PA) (68.2%). Worsening of EIMs after VDZ occurred in 34.8% of patients. There were no statistically significant differences between the worsened EIM (n = 70) and the stable EIM (n = 131) groups in term of age, IBD subtype, or previous and current medical therapy. We found that PA was significantly more common in the worsening EIM group (84.3% vs 59.6%; P < 0.01). Worsening of EIMs was associated with a higher rate of discontinuation of VDZ during study follow-up when compared with the stable EIM group (61.4% vs 44%; P = 0.02). Treatment using VDZ was discontinued specifically because of EIMs in 9.5% of patients. Conclusions Almost one-third of patients had worsening EIMs after VDZ, which resulted in VDZ discontinuation in approximately 10% of patients. Previous biologic use or concurrent immunosuppressant or corticosteroid therapy did not predict EIM course after VDZ.

Abstract Background and Aims We aimed to evaluate the relationship of serum adalimumab trough levels (ATL) with disease activity of inflammatory bowel disease (IBD) patients in a large, well-characterized referral center-based cohort. Methods We compared serum ATL between those with clinical, biochemical, or endoscopic/radiologic disease activity and those without. Results A total of 236 patients with IBD were included. Higher cutoff levels were associated with endoscopic and/or radiologic responses (cutoff value: 5.3 mcg/mL, P = 0.003) compared with improvement in C-reactive protein (cutoff value: 4.3 mcg/mL, P = 0.031). Conclusions Higher cutoff ATL was associated with endoscopic and/or radiologic response.

INTRODUCTION: There are multiple assays for infliximab (IFX) trough level (IFX-TL) and antibody (ATI) measurement. The aims of this study are to examine the correlation and outcomes of IFX-TL and ATI measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and electrochemiluminescence (ECLIA) in inflammatory bowel disease (IBD) patients. METHODS: This was a prospective study of IFX-treated IBD patients undergoing drug monitoring with an ECLIA panel (Esoterix Laboratories). Residual serum samples were used to simultaneously quantify IFX-TL via LC-MS/MS and ATI via an in-house ECLIA (iECLIA) (Mayo Clinic). Both LC-MS/MS and iECLIA have been previously validated. Primary outcomes: IFX-TL and ATI comparison between the two assays. Secondary outcomes: association of IFX-TL and ATI with clinical remission, mucosal healing (MH) (absence of ulcers in Crohn's disease and Mayo endoscopic score ≤1 for ulcerative colitis) and normal serum C-reactive protein (CRP ≤8 mg/L). RESULTS: A total of 151 patients were included (median age 32 years (12-84), 45.7% female) (Table 1). Median IFX-TL was 7 mcg/mL (IQR: 1.3, 19.4) and 6 mcg/mL (IQR: 0.9, 20) via LC-MS/MS and ECLIA, respectively (Spearman correlation coefficient r = 0.975). Median IFX-TL via LC-MS/MS was not significantly different between patients in clinical remission, response and no response (5.7 vs. 8.4 vs. 2.3 mcg/mL, respectively; P = 0.46), but significantly higher in patients who had a normal CRP (11.1 vs. 1.4 mcg/mL; P < 0.001) and in those who achieved MH (13.1 mcg/mL vs. 3.9 mcg/mL; P = 0.01). ATI was detected in 13/142 (9.2%) via iECLIA and 39/151 (25.8%) via ECLIA. The frequency of ATI detection via iECLIA was lower in patients in clinical remission or response than no response (7.3% vs. 9.3% vs. 15.4%; P = 0.68). On the contrary, the frequency of ATI detection via ECLIA was higher in patients with clinical remission (35.7%) than response (18.7%) and comparable to patients who had no clinical response (40%) ( P = 0.05) (Table 2). The frequency of ATI was not significantly different between patients who did and did not achieve MH or had normal CRP using both assays (Table 2). CONCLUSION: IFX-TL was comparable between LC-MS/MS and ECLIA assays. IFX-TL correlated with MH and normal CRP but not clinical remission. Frequency of ATI detection was not significantly associated with outcomes via both methods. ATI detected via iECLIA showed a trend towards correlation with clinical outcomes compared to ECLIA.