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Genetic biomarkers linked to anti TNF response in patients with IBD
A number of genetic polymorphisms are significantly associated with response to treatment with anti-tumor necrosis factor agents in patients with inflammatory bowel disease, according to the results of a meta-analysis published in Alimentary Pharmacology and Therapeutics.
“In order to drive the development of personalized medicine in IBD, we conducted a systematic review of the current knowledge on genetic variants associated with anti-TNF treatment response in patients with IBD,” investigators wrote. “Our aim was to identify potential candidates for further evaluation and putative predictive biomarkers should subsequently be evaluated, validated and eventually adopted for clinical use.”
The researchers included 15 studies in their analysis evaluating a total of 23 polymorphisms in 18 genes.
A functional polymorphism in FCGR3A, which “has been most intensely investigated,” was significantly associated with anti-TNF treatment response in patients with Crohn’s disease based on biological response criteria — specifically, reductions in C-reactive protein levels — but no significant association was observed based on clinical response criteria.
Polymorphisms associated with anti-TNF response in IBD patients based on clinical criteria were identified in:
- TLR2 (rs3804099, OR = 2.17; 95% CI, 1.35-3.47; rs11938228, OR = 0.64; 95% CI, 0.43-0.96);
- TLR4 (rs5030728, OR = 3.18; 95% CI, 1.63-6.21);
- TLR9 (rs352139, OR = 0.43; 95% CI, 0.21-0.88);
- TNFRSF1A (rs4149570, OR = 2.06; 95% CI, 1.02-4.17);
- IFNG (rs2430561, OR = 1.66; 95% CI, 1.05-2.63);
- IL6 (rs10499563, OR = 1.65; 95% CI, 1.04-2.63); and
- IL1B (rs4848306, OR = 1.88; 95% CI, 1.05-3.35).
Furthermore, an exploratory analysis showed patients lacking five genotypes associated with low-response (two in TLR2, two in IL12B and one in IL6) had a positive predictive value of 0.96.
“Only few and weak biomarker candidates were identified for further evaluation of their treatment prediction potential. Thus, the basis for personalized medicine … is not yet available,” the researchers concluded. “Hypothesis-free approaches testing a large number of polymorphisms in large well-characterized cohorts are warranted in order to identify biomarkers which can be used for treatment selection in the clinical setting.” – by Adam Leitenberger
Disclosures: One of the researchers reports consulting for MSD and Janssen.