Baseline levels of dynamic CD4+ T cell adhesion to MAdCAM-1 correlate with clinical response to vedolizumab treatment in ulcerative colitis: a cohort study.

BACKGROUND: While the number of therapeutic options for treating inflammatory bowel diseases (IBD) is increasing, evidence for rational treatment decisions is scarce in many cases. In particular, appropriate biomarkers to predict the response to the anti-α4ß7 integrin antibody vedolizumab are currently lacking. METHODS: We performed a cohort study with 21 patients suffering from ulcerative colitis (UC), in which first-time treatment with vedolizumab was initiated. CD4+ T cells were isolated from the peripheral blood and dynamic adhesion to recombinant mucosal vascular addressin cell adhesion molecule (MAdCAM-)1 in vitro as well as the effect of vedolizumab on such adhesion in vitro was determined. The expression of α4ß1 integrin on peripheral blood CD4+ T cells was quantified by flow cytometry. Electronic patient records were reviewed to determine clinical response to vedolizumab. RESULTS: Dynamic adhesion of peripheral blood CD4+ T cells to MAdCAM-1 and the reduction of adhesion following vedolizumab treatment in vitro were higher and the change in α4ß1 expression on CD4+ T cells was different in vedolizumab responders and non-responders. Responders could be identified with high specificity and positive-predictive value. CONCLUSIONS: Determining dynamic adhesion of CD4+ T cells to MAdCAM-1 and the in vitro response to vedolizumab before treatment initiation or dynamic integrin regulation in the early course of treatment seem to be promising tools to predict the clinical response to vedolizumab therapy. Larger prospective studies are warranted.

Clinical Pharmacist Counselling Improves Long-term Medication Safety and Patient-reported Outcomes in Anti-TNF-treated Patients With Inflammatory Bowel Diseases: The Prospective, Randomized AdPhaNCED Trial.

BACKGROUND: Antitumor necrosis factor (anti-TNF) antibody treatment has led to marked improvements in the management of patients with inflammatory bowel diseases (IBDs). Nevertheless, anti-TNF therapy is associated with potential adverse drug reactions (ADRs). Our prospective, randomized trial investigated the effect of intensified clinical pharmacist counselling in a multidisciplinary team on medication safety in anti-TNF-treated IBD patients. METHODS: Patients with IBD with ongoing anti-TNF treatment were enrolled in our tertiary center AdPhaNCED trial and randomized to either receive conventional standard of care (control group) or additional clinical pharmacist counselling (intervention group) over 12 months. The primary end point consisted of the number and severity of ADRs associated with anti-TNF therapy. Secondary end points included patient satisfaction with medication information and medication safety. RESULTS: One hundred twenty-seven IBD patients were included in this study. Anti-TNF-related ADRs were significantly lower in the intervention compared with the control group (0.20 vs 0.32 [mean] ADR/patient/month, P = .006) after 12 months. The risk of more severe ADRs (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥2) was significantly higher in the control compared with the intervention group (hazard ratio, 0.34; P = .001). The probability of ADR resolution (hazard ratio, 2.02; P < .001) and patient satisfaction with medication information (14.82 vs 11.60; P < .001) were significantly higher in the intervention group compared with the control group. CONCLUSIONS: Our study results demonstrate that intensified pharmacist counselling significantly reduces the occurrence and severity of therapy-related ADRs and improves patient satisfaction. Clinical pharmacists should therefore be part of a holistic approach to IBD care delivered by a multidisciplinary team.

The prospective, randomized AdPhaNCED trial demonstrated that anti-TNF-treated IBD patients had diminished and less severe drug-related adverse reactions and higher patient satisfaction when they received intensified pharmacist counselling in comparison with conventional standard of care over 12 months.