Failing first-line IBD therapy may impact future response
Patients with inflammatory bowel disease (IBD) who had primary nonresponse ─ or inadequate response to the initial loading doses ─ to an anti-tumour necrosis factor (TNF) agent were less likely to respond to second-line biologics compared with those who had secondary loss of response (LOR) or intolerance to the primary therapy, according to a systematic review and meta-analysis presented at the Crohn's & Colitis Congress (CCC) 2018 held recently in Las Vegas, Nevada, US.
“Primary nonresponse to anti-TNF therapy is seen in 35 to 65 percent of IBD patients and another 40 to 60 percent lose responsiveness during the first year of treatment,” said lead author Dr Siddharth Singh from the Division of Gastroenterology at University of California San Diego in La Jolla, California, US. “Physicians struggle with what treatments to recommend for these patients.”
The meta-analysis included eight randomized controlled trials of biologics in IBD patients previously treated with anti-TNF agents. Patient’s response to second-line treatment, or clinical remission, was stratified according to reasons for primary therapy discontinuation (ie, primary nonresponse, LOR, or intolerance). [CCC 2018, abstract P154]
Compared with primary therapy discontinuation due to intolerance, discontinuation due to primary nonresponse was associated with a 24 percent decreased likelihood of clinical remission with second-line biologics (relative risk [RR], 0.76, 95 percent confidence interval [CI], 0.61–0.96).
Also, patients with prior primary nonresponse were 27 percent less likely to achieve clinical remission during induction with second-line biologics than those with secondary LOR, showing signs of disease activity despite ongoing therapy and after an initial response (RR, 0.73, 95 percent CI, 0.56–0.97). In particular, response to the second-line biologic ustekinumab was 36 percent less in those with primary nonresponse vs secondary LOR.
Response to second-line vedolizumab was not significantly different regardless of whether patients discontinued their first-line anti-TNF agents due to primary nonresponse or secondary LOR (RR, 1.16, 95 percent CI, 0.85–1.58).
“Patients with primary nonresponse to anti-TNF agents are less likely to respond to second-line biologics, as compared to patients who discontinued therapy due to secondary LOR or intolerance,” the researchers concluded.
“These findings raise important questions about the biology of IBD, including the pharmacology of anti-TNF in a subset of patients,” said Singh.