High oncostatin M predicts lack of clinical remission for patients with inflammatory bowel disease on tumor necrosis factor α antagonists

Abstract

The interleukin-6 family cytokine, oncostatin-M (OSM) has been associated with response to tumor necrosis factor-α antagonists (anti-TNFs) in small cohorts of patients with inflammatory bowel disease (IBD). We aimed to evaluate the association between plasma OSM concentrations and response to anti-TNFs (infliximab and adalimumab) in both ulcerative colitis (UC) and Crohn's disease (CD). A retrospective cohort study was conducted in patients with IBD with a history of anti-TNF exposure. Blood samples, collected prior to anti-TNF exposure, were analyzed by enzyme-linked immunosorbent assay for the presence and quantity of OSM. Clinical remission was assessed at 1-year post anti-TNF exposure in addition to the occurrence of surgery, hospitalization, corticosteroid use, and adverse drug events. Lastly the threshold OSM plasma concentration associated with anti-TNF non-response was assessed by receiver operator characteristic (ROC) curve analysis. Patients with IBD (CD, n = 82; UC, n = 40) were assessed. In both UC and CD, mean pre-treatment OSM concentrations were significantly lower in those who achieved clinical remission at 1-year (p < 0.0001). A threshold plasma OSM concentration of 168.7 pg/ml and 233.6 pg/ml respectively separated those who achieved clinical remission at 1-year on an anti-TNF from those who did not in CD and UC respectively (CD: area under the receiver operator characteristic curve, AUROC = 0.880, 95% CI 0.79-0.96; UC: AUROC = 0.938, 95% CI 0.87-1.00). High OSM concentrations were associated with anti-TNF discontinuation and use of rescue steroids in CD and UC. High pre-treatment OSM concentrations identify IBD patients at-risk of anti-TNF non-response at 1-year as well as other deleterious clinical outcomes.

Figure 1

Study flowchart.

Figure 2

Mean plasma OSM concentrations in participants with Crohn’s disease and ulcerative colitis stratified by the presence or absence of clinical remission on a TNFA at 1-year are represented by box and whisker plot. Median values (thick horizontal line), 25th and 75th percentile values (box outline), 5–95% confidence intervals (whiskers); *p < 0.0001.

Figure 3

Receiver operator characteristic analysis for mean plasma OSM concentrations for CD (A) and UC (B) participants with and without clinical remission at 1 year on anti-TNF therapy (B). Oncostatin-M, OSM; Crohn’s disease, CD; ulcerative colitis, UC; area under the curve (AUC); confidence interval (CI).