UNASSIGNED: Therapeutic drug monitoring is used to optimize anti-tumour necrosis factor biologic effectiveness in inflammatory bowel disease, but its role with other biological classes is unclear. This study explores relationships between post-induction vedolizumab trough concentrations and biochemical outcomes in a real-world study of individuals with inflammatory bowel disease.
UNASSIGNED: This retrospective analysis of data from a national patient support program between 2018 and 2020, included 436 individuals with Crohn\'s disease or ulcerative colitis receiving vedolizumab. Optimal vedolizumab concentration thresholds (at weeks 6 and 14) were determined based on their ability to predict biochemical normalization (week 30 faecal calprotectin [<250 µg/g], C-reactive protein [<5 mg/l]). Thresholds best associated with each outcome were evaluated in multivariate analyses.
UNASSIGNED: Among patients with Crohn\'s disease, week 6 serum vedolizumab concentrations (>41.65 µg/ml) predicted normalization defined by C-reactive protein: Spearman correlation coefficient [ρ] = -0.26, P = 0.002 and multivariate analysis (MVA)-OR: 3.22, 95% CI: 1.32-7.87, P = 0.01, and at week 14 (>22.25 µg/ml): ρ = -0.38, P < 0.0001, and MVA-OR: 3.21, 95% CI: 1.26-8.17 but not faecal calprotectin. Similarly, among patients with ulcerative colitis, week 6 vedolizumab concentrations (>39.65 g/ml) predicted normalization defined by C-reactive protein: ρ = -0.26, P = 0.005 and MVA-OR: 4.03, 95% CI: 1.30-12.52, P = 0.016, and at week 14 (>17.35 µg/ml): ρ = -0.39, P = 0.0001 and MVA-OR: 6.95, 95% CI: 1.81-26.77, P = 0.005, but not faecal calprotectin.
UNASSIGNED: Induction and post-induction serum vedolizumab were not consistently associated with biochemical normalization. As such, proactive therapeutic drug monitoring for vedolizumab should not be routinely incorporated in a treat to target strategy for inflammatory bowel disease.
UNASSIGNED: NCT04567628.

UNASSIGNED: The risk of serious infection and active tuberculosis in patients with inflammatory bowel disease (IBD) has not been concurrently evaluated based on the use of anti-tumor necrosis factor (TNF)-α agents versus non-anti-TNF biologics (vedolizumab/ustekinumab) in the Korean population.
UNASSIGNED: We compared the risk of serious infection and active tuberculosis in Korean patients with IBD treated with non-anti-TNF biologics (vedolizumab/ustekinumab) or anti-TNF-α agents.
UNASSIGNED: This study was a population-based cohort analysis of nationwide administrative claims data.
UNASSIGNED: Health Insurance Review and Assessment Service claims data (representing 97% of the South Korean population) from between January 2007 and February 2021 were reviewed, and adults with IBD who initiated vedolizumab/ustekinumab or anti-TNF-α treatment (n = 6123) between 2017 and 2020 were enrolled. Intergroup differences in the risk of serious infection requiring hospitalization/emergency department visits or active tuberculosis during the follow-up period were analyzed.
UNASSIGNED: In the patients treated with anti-TNF-α agents or vedolizumab/ustekinumab during a mean follow-up of 1.55 ± 1.05 and 0.84 ± 0.69 years, the incidence rates of serious infection were 9.43/100 and 6.87/100 person-years, respectively. Multivariable analysis showed no significant intergroup difference in the risk of serious infection with vedolizumab/ustekinumab or anti-TNF-α treatment; the adjusted relative risk of vedolizumab/ustekinumab compared with anti-TNF-α agents was 0.81 (95% confidence interval 0.46-1.44, p = 0.478). Among patients treated with anti-TNF-α agents and vedolizumab/ustekinumab, the incidence rates of active tuberculosis were 0.87 and 0.37 per 100 person-years, respectively. The relative risk of vedolizumab/ustekinumab compared with anti-TNF-α agents was 0.31 (95% confidence interval 0.07-1.26, p = 0.101). In a subset analysis comparing vedolizumab and ustekinumab with anti-TNF-α agents, similar results were observed.
UNASSIGNED: In Korean patients with IBD, non-anti-TNF biologics (vedolizumab/ustekinumab) tended to be associated with a lower risk of serious infection or active tuberculosis than anti-TNF-α agents.

OBJECTIVE: Vedolizumab is indicated for the treatment of chronic pouchitis in the European Union. We assessed whether vedolizumab induced mucosal healing (MH) and if MH was associated with clinical improvements.
METHODS: EARNEST, a randomized, double-blind, placebo-controlled study, evaluated vedolizumab efficacy and safety in adults with chronic pouchitis. Centrally read endoscopic and histologic evaluation was performed at baseline, Week (W)14, and W34. Ulcer count, adapted Simple Endoscopic Score for Crohn\'s Disease in the pouch, and Pouchitis Disease Activity Index histologic component were evaluated. Pouchitis Disease Activity Index and Inflammatory Bowel Disease Questionnaire remission at W14 and W34 were compared by MH status at W14.
RESULTS: Following treatment, mean (standard deviation) number of ulcers in vedolizumab-treated patients reduced from 15.1 (16.4) to 5.0 (4.9) at W14 and 2.7 (3.2) at W34 versus placebo-treated patients with corresponding values of 11.8 (11.3), 13.4 (18.4), and 9.7 (13.8) (vedolizumab vs placebo difference [95% confidence interval]: W14: -8.4 [-14.3 to -2.6]; W34: -7.0 [-12.0 to -2.0]). More patients receiving vedolizumab versus placebo achieved reduction in ulcerated pouch surface area (W14: 52.4% vs 20.0%; difference, 32.4 percentage points [p.p] [9.7, 51.4]; W34: 52.1% vs 12.9%; difference, 40.2p.p [15.6, 60.3]), absence of ulceration (W14: 23.8% vs 7.5%; difference, 16.3p.p [1.1, 31.6]; W34: 34.4% vs 15.6%; difference, 18.8p.p [-2.0, 39.5]), Simple Endoscopic Score for Crohn\'s Disease remission (W14: 23.8% vs 7.5%; difference, 16.3p.p [1.1, 31.6]; W34: 34.4% vs 15.6%; difference, 18.8p.p [-2.0, 39.5]), and MH (W14: 16.7% vs 2.5%; difference, 14.2p.p [1.9, 26.4]). Patients with MH at W14 had higher rates of Pouchitis Disease Activity Index and Inflammatory Bowel Disease Questionnaire remission at W14 and W34 than those without.
CONCLUSIONS: Vedolizumab induced endoscopic improvements in patients with chronic pouchitis, which was associated with improved outcomes at W34, particularly in patients achieving MH at W14. (ClinicalTrials.gov number, NCT02790138.).

BACKGROUND: A temporal relationship between vedolizumab and new-onset spondyloarthritis (SpA) has been suggested.
OBJECTIVE: We evaluated the relationship between vedolizumab initiation and development of new-onset SpA in patients with inflammatory bowel disease (IBD) through serial clinical evaluation and magnetic resonance imaging (MRI).
METHODS: A single-centre prospective observational study of 24 patients with IBD. Patients were eligible if they had active ulcerative colitis or Crohn\'s disease (CD), were initiating vedolizumab, had no prior history of arthritis or SpA and were suitable for serial MRI. A rheumatologist performed clinical evaluation prior to the first dose and 8 and 24 weeks. Axial MRI was evaluated by a blinded central reader and performed at baseline 8 and 24 weeks.
RESULTS: Nine tumor necrosis factor (TNF) inhibitor-naïve patients (4 male; mean age 53.2 years; 6 UC; 3 CD) and eight TNF inhibitor-experienced patients (7 male; mean age 48 years; 3 UC; 5 CD) completed all assessments. No patients developed new features of axial arthritis or features of peripheral SpA (inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp)). Both groups demonstrated a good intestinal response.
CONCLUSIONS: Vedolizumab initiation did not induce new features of axial or peripheral SpA after 24 weeks of treatment in TNF inhibitor-experienced or TNF inhibitor-naive patients with IBD.

BACKGROUND: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn\'s disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context.
METHODS: Crohn\'s disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians\' assessment.
RESULTS: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab.
CONCLUSIONS: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

Ustekinumab (UST) is an anti-IL-12/23p40 monoclonal antibody used to treat inflammatory bowel disease. The aim of this retrospective, multicenter study was to investigate the effectiveness of UST administration in achieving remission in patients with ulcerative colitis (UC) and to determine patient characteristics that influence its effectiveness. Of 88 UC patients who received UST from March 2020 to August 2023, 47 with traceable data and for whom 56 weeks had elapsed since the start of treatment received UST to induce remission. The remission rates at 8 weeks were 66% overall, 73.7% for Bio Naïve (never used biologics/JAK inhibitors), and 60.7% for Bio Failure (used biologics/JAK inhibitors) groups. Remission rates at 56 weeks were 70.2% overall, 73.7% for Bio Naïve, and 67.9% for Bio Failure groups. Ustekinumab showed good mid-to-long-term results in the induction of remission of UC in both Bio Naïve and Bio Failure groups. The group showing remission at 8 weeks had a significantly higher non-relapse or continuation rate (proportion of patients with no worsened symptoms necessitating surgery/drug change) at 56 weeks. Predictive factors for achieving remission after UST in UC were female gender, low body mass index, and low lymphocyte-to-monocyte ratio. Thus, UST is effective for moderate-to-severe UC.

OBJECTIVE: We conducted this multicenter, retrospective cohort study aiming to evaluate the effectiveness and safety of vedolizumab (VDZ) and infliximab (IFX) in biologic-naïve patients with moderate-to-severe ulcerative colitis (UC).
METHODS: Biologic-naïve patients with moderate-to-severe UC who were treated with IFX or VDZ for at least 14 weeks at three tertiary hospitals in southwest China between January 2021 and January 2023 were retrospectively included. Efficacy of the biologics was evaluated based on the steroid-free clinical remission rate, clinical remission rate, and mucosal healing rate at Weeks 14 and 52. Adverse events related to biologic use were recorded.
RESULTS: Altogether 122 biologic-naïve patients with moderate-to-severe UC were included. No marked differences in the steroid-free clinical remission rate and clinical remission rate were observed between the two groups at Week 14 or Week 52 (P > 0.05). The VDZ group exhibited a higher mucosal healing rate at Week 14 compared to the IFX group (33.3% vs 16.9%, P = 0.036), while that at Week 52 did not differ between the two groups (65.6% vs 47.1%, P = 0.098). There was no statistically significant difference in the rate of adverse events between the two groups (P = 0.071).
CONCLUSIONS: VDZ and IFX showed comparable clinical efficacy and safety profiles and can be used as viable first-line therapeutic options for biologic-naïve patients with moderate-to-severe UC.

OBJECTIVE: The impact of thiopurine de-escalation while on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab.
METHODS: This multicenter randomized controlled trial recruited UC patients on vedolizumab 300 mg intravenously every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore ≤1) were randomized 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 vedolizumab trough concentrations. Secondary outcomes were clinical relapse (partial Mayo score ≥3 and fecal calprotectin >150 μg/g or increase in Mayo endoscopic subscore ≥1 from baseline), fecal calprotectin remission (<150 μg/g), C-reactive protein remission (<5 mg/L), centrally read endoscopic remission (Mayo endoscopic subscore = 0), histologic remission (Nancy index = 0), histo-endoscopic remission, and adverse events.
RESULTS: In total, 62 patients were randomized to continue (n = 20) or withdraw (n = 42) thiopurine. At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7 μg/mL, interquartile rate [IQR], 12.3-18.5 μg/mL versus 15.9 μg/mL, IQR, 10.1-22.7 μg/mL, respectively, P = 0.36). The continue group had significantly higher fecal calprotectin remission (95.0%, 19/20 versus 71.4%, 30/42; P = .03), histologic remission (80.0%, 16/20 versus 48.6%, 18/37; P = .02), and histo-endoscopic remission (75.0%, 15/20 versus 32.4%, 12/37; P = .002) than the withdrawal group. Histologic activity (hazard ratio [HR], 15.5; 95% confidence interval [CI], 1.6-146.5; P = .02) and prior anti-tumor necrosis factor exposure (HR, 6.5; 95% CI, 1.3-33.8; P = .03) predicted clinical relapse after thiopurine withdrawal.
CONCLUSIONS: Thiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic, and histo-endoscopic activity. Histologic activity and prior anti-tumor necrosis factor exposure may predict disease relapse on thiopurine withdrawal for patients using vedolizumab for UC. Australian and New Zealand Trial Registry, number ACTRN12618000812291.

BACKGROUND: This analysis evaluated the relative performance of vedolizumab and anti-tumor necrosis factor alpha (anti-TNFα) agents in subpopulations of biologic therapy-naive patients with Crohn\'s disease (CD) and assessed whether patients in whom vedolizumab would have a larger treatment effect vs anti-TNFα agents could be identified.
METHODS: Data were from EVOLVE, a real-world, multicountry, retrospective cohort study of patients with inflammatory bowel disease who initiated first-line biologic treatment with vedolizumab (n = 195) or anti-TNFα agents (n = 245). Prediction models for time to clinical remission were developed in vedolizumab- and anti-TNFα-treated patients and used to estimate effect scores, a metric of predicted comparative efficacy, for each patient. Patients were ranked by effect scores and potential subpopulations were investigated. Simplified rules to identify these subpopulations were also developed using classification tree analysis.
RESULTS: Among all patients, median time to clinical remission was 7.8 months (vedolizumab) and 11.1 months (anti-TNFα) (P < 0.05). Among patients in the top 40% of the effect score distribution, the median time to clinical remission was 4.8 months (vedolizumab) vs 18.1 months (anti-TNFα) (adjusted hazard ratio 2.0, 95% confidence interval 1.3-2.9). A simplified rule for identifying a subpopulation more likely to benefit from vedolizumab was based on having an ongoing CD exacerbation, no prior emergency visits, and non-stricturing disease.
CONCLUSIONS: Subpopulations of biologic-naive patients with CD in whom vedolizumab appeared to have a larger effect relative to anti-TNFα agents for the outcome of clinical remission were identified. Validation of the identified subpopulations and simplified rules are warranted to confirm these findings.
RESULTS:
UNASSIGNED: NCT03710486. Graphical Abstract available for this article.

BACKGROUND: In this nationwide study, our objective was to compare the durability of first-line biologics in ulcerative colitis (UC), categorized into monotherapy and combotherapy with immunomodulators.
METHODS: We utilized data from the nationwide epi-IIRN cohort from 2005 to 2020. Durability was defined as consistent treatment without surgery. Comparisons were based on stringent propensity score-matching.
RESULTS: We included 15 111 patients with UC, of whom 2322 (15%) received biologics, with a median follow-up of 7.0 years (interquartile range, 3.8-11.0). The durability rate was similar between pediatric-onset and adults after 1 and 5 years from initiation of treatment (72% and 43% vs 71% and 43%, respectively; P = .8). Durability of adalimumab vs infliximab after 1 or 5 years was similar, whether prescribed as monotherapy (65%/46% vs 63%/33%, respectively; n = 182 matched pairs, P = .3) or combotherapy (78%/56% vs 91%/58%, respectively; n = 46 matched pairs, P = .4). Durability of infliximab was higher as combotherapy (85%/50%) vs monotherapy (69%/42%; n = 174 matched pairs, P = .007), while it was similar for adalimumab (80%/52% vs 74%/52%; n = 53 matched pairs, P = .4). The durability rate was similar for vedolizumab monotherapy (77%/56%) compared with adalimumab monotherapy (69%/52%; n = 125 matched patients, P = .1), and infliximab monotherapy (73%/55% vs 62%/44%; n = 78 matched patients, P = .1). However, combotherapy of antitumor necrosis factors (TNFs) had longer durability than vedolizumab (85%/50% vs 75%/43%, respectively; n = 131 matched pairs, P = .02).
CONCLUSIONS: After 5 years of treatment, 43% of the patients with UC sustained their first biologic, with similar durability in pediatric and adult-onset onset disease. Anti-TNFs had similar durability to vedolizumab and superior durability when prescribed as combotherapy.