Dataset Information

Dissecting common and unique effects of anti-?4?7 and anti-tumor necrosis factor treatment in ulcerative colitis.

ABSTRACT:

Background and aims

Vedolizumab is an anti-?4?7 antibody approved for the treatment of ulcerative colitis (UC). Although it is assumed that vedolizumab blocks intestinal homing of lymphocytes, its effects on different intestinal cell populations are not fully stablished. In order to establish the unique mechanisms of action of vedolizumab in UC patients, we compared its effects to those induced by anti-tumor necrosis factor (TNF).

Methods

Patients with active UC (endoscopic Mayo score >1) starting vedolizumab (n=33) or anti-TNF (n=45) and controls (n=22) were included. Colon biopsies (at weeks 0, 14 and 46) and blood samples (at weeks 0, 2, 6,14, 30 and 46) were used for cell phenotyping, transcriptional analysis (qPCR), and to measure receptor occupancy.

Results

Vedolizumab, in contrast to anti-TNF, significantly reduced the proportion of ?4?7 + cells within intestinal T subsets while preserving the percentage of ?4?7 + plasma cells. The marked decrease in ?4?7 did not change the percentage of colonic ?E?7 + cells (at 46 weeks). Both vedolizumab and anti-TNF significantly downregulated inflammation-related genes in the colon of responders (Mayo score <2). Moreover, both treatments significantly decreased the percentage of intestinal, but not blood, total lymphocytes (T and plasma cells), as well as the proportion of ?4?1 + cells within intestinal T lymphocytes.

Conclusions

Our data shows that while vedolizumab and anti-TNF block two unrelated targets, they induce remarkably similar effects. On the other hand, vedolizumab's unique mechanism of action relies on blocking intestinal trafficking of ?4?7 T cells, despite effectively binding to B and plasma cells that express ?4?7.

SUBMITTER: Veny M

PROVIDER: S-EPMC7944518 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Dissecting Common and Unique Effects of Anti-α4β7 and Anti-Tumor Necrosis Factor Treatment in Ulcerative Colitis.

Veny Marisol M Garrido-Trigo Alba A Corraliza Ana M AM Masamunt Maria C MC Bassolas-Molina Helena H Esteller Miriam M Arroyes Montserrat M Tristán Eva E Fernández-Clotet Agnès A Ordás Ingrid I Ricart Elena E Esteve Maria M Panés Julian J Salas Azucena A

Journal of Crohn's & colitis 20210301 3

<h4>Background and aims</h4>Vedolizumab is an anti-α4β7 antibody approved for the treatment of ulcerative colitis [UC]. Although it is assumed that vedolizumab blocks intestinal homing of lymphocytes, its effects on different intestinal cell populations are not fully stablished. In order to establish the unique mechanisms of action of vedolizumab in UC patients, we compared its effects to those induced by anti-tumour necrosis factor [TNF].<h4>Methods</h4>Patients with active UC [endoscopic Mayo ...[more]

PMID: 32926095

Similar Datasets

Project description:BackgroundEfficacy of tumor necrosis factor alpha (TNF-α) blockers for treatment of ulcerative colitis that is unresponsive to conventional therapy is unclear due to recent studies yielding conflicting results.AimTo assess the efficacy and safety of anti-TNF-α agents for treatment of ulcerative colitis patients who were intolerant or refractory to conventional medical therapy.MethodsPubmed, Embase, and the Cochrane database were searched. Analysis was performed on randomized controlled trials that assessed anti-TNF-α therapy on ulcerative colitis patients that had previously failed therapy with corticosteroids and/or immunosuppressants. The primary outcome focused on was the frequency of patients that achieved clinical remission. Further trial outcomes of interest included rates of remission without patient use of corticosteroids during the trial, extent of mucosal healing, and the number of cases that resulted in colectomy and serious side effects.ResultsEight trials from seven studies (n = 2122) met the inclusion criteria and were thus included during analysis. TNF-α blockers demonstrated clinical benefit as compared to placebo control as evidenced by an increased frequency of clinical remission (p<0.00001), steroid-free remission (p = 0.01), endoscopic remission (p<0.00001) and a decrease in frequency of colectomy (p = 0.03). No difference was found concerning serious side effects (p = 0.05). Three small trials (n = 57) comparing infliximab to corticosteroid treatment, showed no difference in frequency of clinical remission (p = 0.93), mucosal healing (p = 0.80), and requirement for a colectomy (p = 0.49). One trial compared infliximab to cyclosporine (n = 115), wherein no difference was found in terms of mucosal healing (p = 0.85), colectomy frequency (p = 0.60) and serious side effects (p = 0.23).ConclusionTNF-α blockers are effective and safe therapies for the induction and maintenance of long-term remission and prevention of treatment by colectomy for patients with refractory ulcerative colitis where conventional treatment was previously ineffective. Furthermore, infliximab and cyclosporine were found to be comparable for treating acute severe steroid-refractory ulcerative colitis.