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Background and Objectives : The subcutaneous (SC) formulation of vedolizumab has proven to be effective for the maintenance of remission after intravenous induction. Little is known about the efficacy of switching from intravenous maintenance treatment to SC. We aimed to assess the real-world efficacy of switching to SC treatment and to assess the impact of a baseline treatment regimen. Materials and Methods : In this observational cohort study, adult patients with inflammatory bowel disease who were switched to SC vedolizumab maintenance treatment were enrolled. Patients after intravenous induction and patients who switched from intravenous maintenance treatment (every 8 weeks or every 4 weeks) were included. The SC vedolizumab dosing was 108 mg every 2 weeks, regardless of the previous regimen. The clinical, biochemical, and endoscopic disease activity parameters and vedolizumab serum concentrations at the time of the switch and at the follow-up were assessed. Results : In total, 135 patients (38% Crohn's disease, 62% ulcerative colitis) were switched to SC vedolizumab treatment. The median time to the first follow-up (FU) was 14.5 weeks (IQR 12-26), and the median time to the second FU was 40 weeks (IQR 36-52). Nine patients (7%) discontinued SC vedolizumab treatment, with two-thirds of them discontinuing due to active disease. In all dosing regimens, there were no significant changes in the clinical scores and CRP at the baseline and first and second FUs. Clinical and biochemical remission appeared to be maintained irrespective of the previous dosing regimen. Conclusions : The results of this real-world study suggest that the maintenance of clinical and biomarker remission can be achieved in patients who switched from intravenous to SC vedolizumab. The baseline vedolizumab dosing regimen (every 4 weeks versus every 8 weeks) did not have an impact on outcomes.

Background & Aims: Magnetic resonance enterography (MRE) is having an increasing role in Crohn's disease; however, fully validated indices are needed. We evaluated the responsiveness of 4 MRE indices in luminal Crohn's disease., Methods: Paired MRE images (pretreatment and post-treatment at weeks 12 or 14) from 41 patients were scored by 3 blinded radiologists. Disease activity was scored for 4 MRE indices (magnetic resonance index of activity [MaRIA], simplified MaRIA, London index, and London extended index) and a 100-mm visual analog scale (VAS) of overall disease activity. The criterion for change was an improvement by at least one half of an SD in the VAS after treatment. Responsiveness was evaluated using the standardized effect size (SES). Longitudinal validity was evaluated using correlations between changes in MRE index scores and disease activity measures including endoscopy and the VAS., Results: The SES was 1.17 (95% CI, 0.56-1.77) for the simplified MaRIA, 0.98 (95% CI, 0.42-1.55) for the MaRIA, 0.95 (95% CI, 0.38-1.51) for the London extended index, and 0.85 (95% CI, 0.31-1.39) for the London index. The simplified MaRIA was significantly more responsive than the London index (ΔSES, 0.32; 95% CI, 0.05-0.58) but not the MaRIA (ΔSES, 0.18; 95% CI, -0.01 to 0.38) or the London extended index (ΔSES, 0.22; 95% CI, -0.05 to 0.50). Correlations with endoscopy (simplified MaRIA: r = 0.72) were not different from correlations with the VAS (London extended index: r = 0.70)., Conclusions: Evaluated MRE indices showed moderate-to-large responsiveness and are suitable for use in clinical trials. The simplified MaRIA may be preferred because of its responsiveness and nonreliance on gadolinium administration., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Some patients with Crohn's disease do not achieve remission with the approved maintenance dosing of ustekinumab every 8 weeks, possibly due to insufficient drug exposure. We aimed to study the exposure-response relationship for endoscopic remission and biomarker normalization with ustekinumab dose escalation to every 4 weeks., Methods: Out of 135 consecutive patients, 44 with active Crohn's disease despite standard maintenance dosing [at least one of C-reactive protein (CRP) >5 mg/L, fecal calprotectin >100 mg/kg, simple endoscopic score (SES) for Crohn's disease >3] underwent dose escalation to every 4 weeks. Subsequent endoscopic remission (SES-CD ≤3 without ulceration) and biomarker normalization were compared against ustekinumab concentrations., Results: Dose escalation led to endoscopic remission in 28.6% (8/28), CRP normalization 29.2% (7/24) and fecal calprotectin normalization 51.7% (15/29) of patients. Ustekinumab concentrations after escalation were higher in patients with endoscopic remission (6.90 vs. 4.29 mg/L; P = 0.025) and fecal calprotectin normalization (6.65 vs. 3.74 mg/L; P = 0.001). A threshold of 6.00 mg/L identified endoscopic remission [area under the receiver operating curve (AUROC): 0.775; 95% confidence interval (CI), 0.551-0.999), a threshold of 4.40 mg/L (AUROC 0.755; 95% CI, 0.545-0.964) two months after escalation identified patients with fecal calprotectin normalization at the end of follow-up. Concentrations <3.5 mg/L after escalation precluded endoscopic remission or biomarker normalization., Conclusion: Endoscopic remission was associated with higher ustekinumab concentrations after dose escalation. Patients with concentrations <3.5 mg/L after dose escalation are unlikely to achieve endoscopic remission or biomarker normalization., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Little is known about the relationship between ustekinumab exposure during the first 2 weeks of treatment and outcomes of patients with Crohn's disease (CD). We investigated the relationship between serum concentrations of ustekinumab during the first 2 weeks of treatment and endoscopic and biochemical remission in patients with CD., Methods: In a prospective observational study, we measured concentrations of ustekinumab in serum samples from 41 consecutive patients who started treatment with ustekinumab (approximately 6 mg/kg, intravenously, then 90 mg every 8 weeks), due to endoscopic markers of active CD, at a single center from October 2017 through January 2019. We measured ustekinumab exposure parameters during the first 2 weeks (peak concentration measured immediately after intravenous infusion, week 2 concentration, and area under the curve through week 2). We investigated the correlation between these parameters and endoscopic remission (simple endoscopic score for CD scores of 3 or less without ulceration, assessed centrally) and biochemical remission (level of fecal calprotectin below 100 mg/kg) using the Mann-Whitney U test., Results: Endoscopic remission was achieved in 10 patients (24.4%) at week 24; biochemical remission was achieved in 17 patients (41.5%) at week 8, 17 patients (41.5%) at week 16, and 21 patients (51.2%) at week 24. Peak concentrations associated with endoscopic remission (area under the receiver operating characteristic curve, 0.717; 95% CI, 0.517-0.916); 6 of 13 patients (46%) with peak concentrations above 105 μg/mL (upper tercile) achieved endoscopic remission, compared with only 1 of 14 patients (7%) with peak concentrations below 88 μg/mL (lower tercile). All exposure parameters during the first 2 weeks were associated with biochemical remission. There was no significant difference between the associations of peak concentrations, week-2 concentrations, area under the curve through week 2, or later exposure measures (at weeks 4 and 8) with biochemical or endoscopic remission., Conclusions: In a prospective study, we found that serum concentrations of ustekinumab as early as 1 hour after intravenous infusion might be used to identify patients with CD most likely to achieve endoscopic remission. This early measurement might be used to optimize treatment of CD., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)