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IBD patients with certain clinical, serological, genetic markers more likely to respond poorly to anti-TNFs
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Primary nonresponse to anti-TNF therapy was more likely in patients with inflammatory bowel disease with certain clinical, serologic and genetic markers, according to new research. These predictors could be used to help personalize IBD management.
Of note, investigators found that colonic involvement was “a key predictor” of primary nonresponse in patients with Crohn’s disease.
“As IBD physicians and their patients face an ever-expanding option of treatment options for IBD we will need to address how to position these and get the right drug to the right patient and avoid unnecessary exposure when drugs are unlikely to work,” Dermot P. B. McGovern, MD, PhD, of the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute and the department of medicine at Cedars-Sinai Medical Center, Los Angeles, told Healio Gastroenterology. “This is one of the goals of a more precise approach to managing IBD.”
Dermot P. B. McGovern
McGovern and colleagues retrospectively evaluated 314 patients with Crohn’s disease and 145 patients with ulcerative colitis within a genetics registry who had been treated with anti-TNFs. Among Crohn’s patients, 16.2% had primary nonresponse, 57% had secondary nonresponse and 26.8% had durable response. Among UC patients, 29.7% had primary nonresponse, 51% had secondary nonresponse and 19.3% had durable response. Patients with UC were more likely to be primary nonresponders than patients with Crohn’s disease (OR = 2.2; 95% CI, 1.37-3.46).
Multivariate analysis revealed associations between colonic involvement (OR = 8; 95% CI, 1.46-43.91), receiving anti-TNF monotherapy (OR = 4.9; 95% CI, 1.32-18.34) and smoking (OR = 4; 95% CI, 0.95-16.99) and an increased risk for primary nonresponse to anti-TNFs among patients with Crohn’s disease. Conversely, no variables were significantly associated with primary nonresponse in UC patients in multivariate analysis.
Further, multivariate analysis revealed an association between high anti–nuclear cytoplasmic antibody (ANCA) levels and time to loss of response in patients with Crohn’s disease (HR = 1.006; 95% CI, 1-1.01). In UC patients, testing negative for anti–Escherichia coli outer membrane protein C (anti-OmpC; HR = 0.4; 95% CI, 0.15-1.14) and positive for ANCA (HR = 1.6; 95% CI, 1.03-2.64) were associated with time to loss of response to anti-TNFs. A positive family history of IBD (HR = 1.3; 95% CI, 1.01-1.71) was the only variable linked to time of loss of response to anti-TNFs among all IBD patients.
Finally, the investigators found a number of known IBD susceptibility single-nucleotide polymorphisms and variants in immune-mediated genes linked to primary nonresponse or time to loss of response in all IBD patients.
“This study builds on other work that will help develop precision treatment algorithms for IBD,” McGovern said.
He and colleagues concluded that prospective studies including therapeutic drug monitoring are needed to validate these findings and to evaluate if these variables can predict response to other drug classes.
“Studies such as ours provide building blocks for the development of personalized medicine or patient-tailored care in IBD,” they wrote. “Identifying groups of individuals less likely to respond to anti-TNFs will become increasingly important as additional therapeutic modalities become available for the treatment of IBD.” – by Adam Leitenberger
Disclosures: McGovern reports he is a consultant for Janssen and UCB. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Editor's note: This article was updated on June 13 with additional information from the study author.
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