P154 PRIMARY NON-RESPONSE TO TUMOR NECROSIS FACTOR ANTAGONISTS IS ASSOCIATED WITH INFERIOR RESPONSE TO SECOND-LINE BIOLOGICS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES: A SYSTEMATIC REVIEW AND META-ANALYSIS

2018 ◽  
Vol 154 (1) ◽  
pp. S81-S82
Author(s):  
Siddharth Singh ◽  
John George ◽  
Brigid S. Boland ◽  
Niels Vande Casteele ◽  
William J. Sandborn
2018 ◽  
Vol 12 (6) ◽  
pp. 635-643 ◽  
Author(s):  
Siddharth Singh ◽  
John George ◽  
Brigid S Boland ◽  
Niels Vande Casteele ◽  
William J Sandborn

Abstract Background and Aims We sought to analyze whether response to a second-line biologic varies depending on the reason for discontinuation of the primary anti-TNF agent (primary non-response [PNR], secondary loss of response [LOR] after initial response, or intolerance), through a systematic review and meta-analysis. Methods Through a systematic search through May 31, 2017, we identified eight randomized controlled trials [RCTs] of biologics in patients with IBD with prior exposure to anti-TNF agents, that stratified response to second-line therapy by reason for discontinuing primary anti-TNF therapy [PNR vs. LOR vs. intolerance]. We estimated relative risk [RR] (and 95% confidence interval [CI]) of achieving clinical remission in patients with PNR as compared with patients with LOR, and intolerance, through random effects meta-analysis. Results As compared with patients who discontinued prior anti-TNF due to intolerance, patients with prior PNR were 24% less likely to achieve remission with second-line biologics (RR,0.76 [0.61–0.96]). As compared with patients who discontinued prior anti-TNF due to LOR, patients with prior PNR were 27% less likely to achieve remission with induction therapy with second-line biologics (RR,0.73 [0.56–0.97]), particularly to ustekinumab (RR,0.64 [0.52–0.80]). There was no difference in response to vedolizumab in patients with prior PNR or LOR to anti-TNF agents (RR,1.16 [0.85–1.58]). Conclusion Patients with PNR to anti-TNF agents are less likely to respond to second-line non-TNF biologics, as compared with patients who discontinued therapy due to secondary LOR or intolerance. This may be attributed to underlying pharmacokinetics and pharmacodynamics of anti-TNF agents in patients with PNR.


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