TY - JOUR

T1 - Putative biomarkers of vedolizumab resistance and underlying inflammatory pathways involved in IBD

AU - Soendergaard, Christoffer

AU - Seidelin, Jakob Benedict

AU - Steenholdt, Casper

AU - Nielsen, Ole Haagen

PY - 2018

Y1 - 2018

N2 - Objectives: Characterise the circulating inflammatory cytokine pattern among patients failing consecutive anti-tumour necrosis factor (anti-TNF) and anti-integrin treatments to identify predictors of response.Methods: A retrospective single-centre cohort study of 28 patients with inflammatory bowel disease (IBD) receiving anti-integrin therapy (vedolizumab) subsequent to the failure of anti-TNF treatment was conducted. Blood samples were obtained immediately prior to initiation of vedolizumab therapy, and the response to treatment was evaluated after completion of the 14-week induction regimen. Multiplex ELISA was applied to quantify 47 preselected plasma proteins based on their putative involvement in the inflammatory process in IBD.Results: Anti-TNF and vedolizumab non-responders (n=20) had significantly higher levels of circulating interleukin (IL)-6 than anti-TNF non-responders with subsequent response to vedolizumab (n=8): median 9.5 pg/mL versus 5.9 pg/mL, p<0.05. Following stratification by diagnosis, patients with Crohn's disease who failed vedolizumab therapy (n=7) had higher soluble CD40 ligand (sCD40L) than responders (n=4): 153.0 pg/mL versus 45.5 pg/mL, p<0.01; sensitivity 100% (95% CI 59% to 100%), specificity 100% (95% CI 40% to 100%). Osteocalcin was higher among patients with ulcerative colitis responding to vedolizumab (n=4) compared with those not responding (n=13): 4219 pg/mL versus 2823 pg/mL, p=0.01; sensitivity 85% (95% CI 55% to 98%), specificity 100% (95% CI 40% to 100%).Conclusions: Patients with IBD failing vedolizumab induction and anti-TNF therapy have persistent IL-6 pathway activity, which could be a potential alternative treatment target. sCD40L, osteocalcin and the IL-6 pathway activity might be predictors for response to vedolizumab.

AB - Objectives: Characterise the circulating inflammatory cytokine pattern among patients failing consecutive anti-tumour necrosis factor (anti-TNF) and anti-integrin treatments to identify predictors of response.Methods: A retrospective single-centre cohort study of 28 patients with inflammatory bowel disease (IBD) receiving anti-integrin therapy (vedolizumab) subsequent to the failure of anti-TNF treatment was conducted. Blood samples were obtained immediately prior to initiation of vedolizumab therapy, and the response to treatment was evaluated after completion of the 14-week induction regimen. Multiplex ELISA was applied to quantify 47 preselected plasma proteins based on their putative involvement in the inflammatory process in IBD.Results: Anti-TNF and vedolizumab non-responders (n=20) had significantly higher levels of circulating interleukin (IL)-6 than anti-TNF non-responders with subsequent response to vedolizumab (n=8): median 9.5 pg/mL versus 5.9 pg/mL, p<0.05. Following stratification by diagnosis, patients with Crohn's disease who failed vedolizumab therapy (n=7) had higher soluble CD40 ligand (sCD40L) than responders (n=4): 153.0 pg/mL versus 45.5 pg/mL, p<0.01; sensitivity 100% (95% CI 59% to 100%), specificity 100% (95% CI 40% to 100%). Osteocalcin was higher among patients with ulcerative colitis responding to vedolizumab (n=4) compared with those not responding (n=13): 4219 pg/mL versus 2823 pg/mL, p=0.01; sensitivity 85% (95% CI 55% to 98%), specificity 100% (95% CI 40% to 100%).Conclusions: Patients with IBD failing vedolizumab induction and anti-TNF therapy have persistent IL-6 pathway activity, which could be a potential alternative treatment target. sCD40L, osteocalcin and the IL-6 pathway activity might be predictors for response to vedolizumab.

U2 - 10.1136/bmjgast-2018-000208

DO - 10.1136/bmjgast-2018-000208

M3 - Journal article

C2 - 29915667

VL - 5

JO - B M J Open Gastroenterology

JF - B M J Open Gastroenterology

SN - 2054-4774

IS - 1

M1 - e000208

ER -