Low TNF production and low TREM1 expression as negative predictors for remission under adalimumab therapy in Crohn's Disease patients

Abstract Background Approximately one third of IBD patients show a primary non-response to anti-TNF therapy. An individualized treatment approach requires clinical predictors. Our previous study showed that LPS-stimulated TNF production can be used to predict response to infliximab in Crohn′s Disease patients. The expression of the myeloid receptor TREM1 is also known as a potential predictive marker for anti-TNF therapy response. The aim of this study is to compare these two predictors for response to adalimumab. Methods In this prospective observational study 24 adults with Crohn′s Disease starting adalimumab treatment were included. Disease activity was assessed clinically (Harvey-Bradshaw-Index (HBI)), through lab results (leukocytes, C-reactive protein, calprotectin) and per ultrasound (Limberg-Score) at the time point of adalimumab induction, after 6 and 12 weeks. TNF-production of LPS-stimulated peripheral blood mononuclear cells was measured via ELISA at the baseline. The expression of TREM1 and its soluble isoform TREM1sv was quantified from whole blood RNA via qPCR. Primary endpoints were clinical response after week 6 and 12. Response was defined as a decrease in HBI ≥2, remission as HBI <5. Cut-off values for low- and high-producers were defined via receiver operating characteristic (ROC). Results were tested for significance with chi²-Test. Results Of 24 recruited patients 18 have currently reached week 12. 5 patients have not reached remission within 6 weeks, 4 have not reached remission within 12 weeks. TNF production and TREM1 expression differed among patients at baseline. After definition of a cut-off value 6 low-TNF-producers, 8 low-TREM1-producers and 7 low-TREM1sv-producers could be identified. Three out of 6 low-TNF-producers were in non-remission after 6 weeks compared to 2 out of 12 high-TNF-producers (p=0.1366). Five out of 8 low-TREM1-producers were in non-remission after 6 weeks compared to 0 out of 9 high-TREM1-producers (p=0.0048, 1 missing value). Four out of 7 low-TREM1sv-producers were in non-remission after 6 weeks compared to 1 out of 10 high-TREM1sv-producers (p=0.0488, 1 missing value). Figure 1) Remission after 6 weeks of adalimumab treatment - low vs. high TNF Figure 2) Remission after 6 weeks of adalimumab treatment - low vs. high TREM1 Figure 3) Remission after 6 weeks of adalimumab treatment - low vs. high TREM1sv Conclusion Low TREM1 and TREM1sv expression seem to be stronger predictors for non-remission after 6 weeks of adalimumab treatment compared to TNF-production. These results are to be validated with increased patient numbers.