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IBD patients with primary non-response to anti-TNF less likely to respond to second biologic
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LAS VEGAS — Patients with inflammatory bowel disease who discontinued their first-line anti-TNF therapy due to primary non-response rather than secondary loss of response or intolerance were less likely to respond to second-line biologics, according to new research presented at the Crohn’s & Colitis Congress.
Siddharth Singh, MD, MS, of the division of gastroenterology at University of California, San Diego, and colleagues concluded that this finding could be due to the pharmacokinetics and pharmacodynamics of anti-TNF therapy in these patients.
“Patients are deemed to have primary non-response due to failure to respond clinically to three induction doses (as defined in clinical trials included in this meta-analysis),” Singh told Healio Gastroenterology and Liver Disease. “This may be due to inadequate drug levels (pharmacokinetic failure) in some patients with very severe disease or may be failure despite adequate levels (mechanistic failure, a definition toward which we are moving more and more in clinical practice).”
To determine whether a patient’s response to a second-line biologic is affected by their reason for stopping primary anti-TNF therapy, Singh and colleagues performed a systematic review of research published through May 2017, ultimately including eight randomized controlled trials in their meta-analysis. All trials evaluated biologics in patients with IBD who tried a previous anti-TNF, and stratified their response based on their reason for stopping the primary therapy (primary non-response, secondary loss of response or intolerance).
The investigators found that patients with primary non-response to anti-TNF showed 24% lower odds of achieving remission with a second-line biologic compared with patients who stopped primary therapy due to intolerance (RR = 0.76; 95% CI, 0.61-0.96).
Similarly, patients with primary non-response showed 27% lower odds of achieving remission with a second-line biologic compared with patients who stopped primary therapy due to loss of response (RR = 0.73; 95% CI, 0.56-0.97).
The researchers noted this association was especially strong with Stelara (ustekinumab, Janssen; RR = 0.64; 0.52-0.8), but saw no difference in response to Entyvio (vedolizumab, Takeda) in patients with primary non-response or loss of response to anti-TNF therapy (RR = 1.16; 95% CI, 0.85-1.58).
“So, for patients who have had primary non-response anti-TNF, particularly those due to low trough levels (or if levels were not checked), our findings suggest that if non-TNF biologics are tried, an aggressive approach (using a higher dose, combination with immunomodulators, and proactively monitoring drug levels) may be preferred,” Singh said. “Additionally, personalized approaches to identify predictors of response to specific therapies is warranted, particularly for those deemed to have mechanistic failure to anti-TNF agents.” – by Adam Leitenberger
Reference:
Singh S, et al. P154. Presented at: Crohn’s & Colitis Congress; Jan. 19-20, 2018; Las Vegas, NV.
Disclosures: Singh reports he has served as a consultant for AbbVie and has received research funding from the American College of Gastroenterology, the Crohn’s and Colitis Foundation, Pfizer and AbbVie. Please see the abstract for a list of all other authors’ relevant financial disclosures.