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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.
Singh et al. (Sun,) studied this question.