Article Text
Abstract
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.
- Ibd
- gastrointestinal immune response
- crohn’s disease
- ulcerative colitis
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Footnotes
Contributors CaS, JBS and OHN provided access to the study material and conceived the broad scope of the project. ChS analysed the data and drafted the manuscript in close collaboration with the remaining authors. All authors have read and approved the manuscript.
Funding The applied ELISA plates for the study were sponsored by Takeda Pharmaceuticals as part of the unsolicited, independent Investigator Initiated Sponsored Research (IISR) programme.
Competing interests None declared.
Patient consent Not required.
Ethics approval The retrospective cohort study was approved by the Scientific Ethics Committee of the Copenhagen Capital Region (H-16026084) and the Danish Data Protection Agency (HGH-2016–077).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All cytokine measurements not included in the study are available. The data may be accessed by the investigators.