Safety, efficacy and pharmacokinetics of vedolizumab in patients with simultaneous exposure to an anti-tumour necrosis factor.

Data on combination-biologic treatment in (IBD) are still scant. To explore outcomes of patients co-exposed to anti-TNF and vedolizumab. Patients starting vedolizumab having measurable anti-TNF levels after recently stopping adalimumab/infliximab ('VDZ-aTNF' group), were compared with control vedolizumab patients in a retrospective 1:2 matched case-control study. Seventy-five patients were included (25 VDZ-aTNF, 50 VDZ). Adverse events were experienced by 9/25 VDZ-aTNF compared to 13/50 VDZ patients (P = 0.4, follow-up 14 weeks in all). Week 14 clinical remission was attained in 10/25 (40%) of VDZ-aTNF patients versus 23/50 (46%) of VDZ patients (OR = 0.8, 95% CI 0.3-2.1, P = 0.6) and clinical response in 19/25 (76%) versus 39/50 (78%) respectively (OR = 0.9, 95% CI 0.3-2.7, P = 0.8). Corticosteroid-free remission and corticosteroid-free response were experienced by 30% and 54%, respectively, of the entire cohort, and were similar between the two groups. Vedolizumab drug concentrations at week 2, 6 and 14 were similar among VDZ-aTNF and VDZ patients (P > 0.5). Multi-variable analysis showed independent association of some vedolizumab drug-levels time-points with baseline albumin and weight, but not with anti-TNF co-exposure. In a prospective study of a separate cohort of patients starting infliximab (n = 12), the percentage of α4β7+ memory T cells, slightly but nonsignificantly increased throughout weeks 0, 2 to 14 (26 ± 2.3%, 27.8 ± 2.9%, 29.5 ± 2.6% respectively, P = 0.06). Vedolizumab/anti-TNF co-exposure did not generate new safety signals during 14-weeks induction, nor did it reduce efficacy or alter vedolizumab pharmacokinetics. These observations may aid the design of future co-biologics trials and also suggest that a deliberate waiting-interval between anti-TNF cessation and subsequent vedolizumab initiation may not be warranted.

Ben-Horin S ，Ungar B ，Kopylov U ，Lahat A ，Yavzori M ，Fudim E ，Picard O ，Peled Y ，Eliakim R ，Del Tedesco E ，Paul S ，Roblin X ... -  《-》

Comparative efficacy and safety of vedolizumab and infliximab in ulcerative colitis after failure of a first subcutaneous anti-TNF agent: a multicentre cohort study.

Few data exist to help select a second biologic agent in patients with refractory ulcerative colitis (UC). To compare the efficacy of infliximab (IFX) and vedolizumab (VDZ) in UC patients who failed a first subcutaneous anti-tumor necrosing factor (TNF) agent. Consecutive UC patients from 12 French centres starting IFX or VDZ after at least one injection of adalimumab or golimumab have been included in a retrospective study. Outcomes were clinical remission at week 14, survival without treatment discontinuation and survival without UC-related event. Among the 225 patients included, clinical remission at week 14 was achieved in 40/154 (26%) patients treated with IFX and in 35/71 (49%) treated with VDZ (P = 0.001). After a propensity score matching analysis, this difference remained significant (odds ratio: 1.67; 95% confidence interval: 1.08-2.56; P = 0.02). With a median follow-up of 117 weeks, survival rates without treatment discontinuation at years 1 and 3 were 50% and 29% with IFX, and 80% and 55% with VDZ, respectively (P < 0.001). Regarding survival without UC-related event, they were 49% and 27% with IFX, and 74% and 52% with VDZ (P < 0.01). After failure of a first subcutaneous anti-TNF agent, UC patients were more likely to achieve clinical remission with VDZ than those treated with IFX. Although due to prescription habits patients in the IFX group had a significantly more severe disease, these differences remained after adjustments and subgroup analyses. Such results have to be confirmed prospectively and warrant dedicated head-to-head trials.

Hupé M ，Rivière P ，Nancey S ，Roblin X ，Altwegg R ，Filippi J ，Fumery M ，Bouguen G ，Peyrin-Biroulet L ，Bourreille A ，Caillo L ，Simon M ，Goutorbe F ，Laharie D ... -  《-》

Efficacy and Safety of Vedolizumab for Induction of Remission in Inflammatory Bowel Disease-the Israeli Real-World Experience.

Kopylov U ，Ron Y ，Avni-Biron I ，Koslowsky B ，Waterman M ，Daher S ，Ungar B ，Yanai H ，Maharshak N ，Ben-Bassat O ，Lichtenstein L ，Bar-Gil Shitrit A ，Israeli E ，Schwartz D ，Zittan E ，Eliakim R ，Chowers Y ，Ben-Horin S ，Dotan I ... -  《-》

Outcome of elective switching to vedolizumab in inflammatory bowel disease patients under tumor necrosis factor antagonist-maintained clinical remission.

Vedolizumab (VDZ) has been used in inflammatory bowel disease (IBD) patients who failed anti-tumor necrosis factor (TNF) therapy. This study was to examine long-term outcome of IBD patients switching to VDZ from anti-TNF agents for reasons other than failure of therapy. Inflammatory bowel disease patients at the University of Chicago IBD center who were in clinical remission with anti-TNF therapy and then electively changed to VDZ due to reasons other than loss of response were retrospectively analyzed. The primary outcome was the durability of clinical remission maintained by VDZ as assessed by Kaplan-Meier survival analysis. The proportion of patients in clinical and endoscopic remission at 6-12 months after switching to VDZ therapy was analyzed. A total of 41 patients (36 with Crohn's disease and 5 with ulcerative colitis) met the inclusion criteria and were in clinical remission at the time of switch. The majority of patients switched therapy due to adverse effects (56.1%) or infections (14.6%). During a median duration of 30 months (range 7-52) of VDZ therapy, 34 (82.9%) were in VDZ-maintained clinical remission. One (2.4%) and four (9.8%) patients discontinued VDZ due to flare and adverse effects, respectively. Endoscopic remission was present in 25 of 30 patients (83.3%) who had a follow-up colonoscopy. Vedolizumab was effective and safe in maintaining remission in IBD patients who switched from anti-TNF agents due to reasons other than failure of therapy. Our results suggest that switching anti-TNF remitters to VDZ treatment is a safe practice in specific patient populations.

Wang Y ，Wang J ，Pekow J ，Dalal S ，Cohen RD ，Ollech J ，Israel A ，Shogan BD ，Micic D ，Cannon L ，Umanskiy K ，Hurst R ，Hyman N ，Rubin DT ，Sakuraba A ... -  《-》

Comparative efficacy and safety of subcutaneous infliximab and vedolizumab in patients with Crohn's disease and ulcerative colitis included in randomised controlled trials.

While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn's disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited. Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease. Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC. We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals [CIs]) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year. IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.

Peyrin-Biroulet L ，Arkkila P ，Armuzzi A ，Danese S ，Ferrante M ，Jordi Guardiola ，Jahnsen J ，Louis E ，Lukáš M ，Reinisch W ，Roblin X ，Smith PJ ，Kwon T ，Kim J ，Yoon S ，Kim DH ，Atreya R ... -  《BMC GASTROENTEROLOGY》