Background and Aims: We sought to analyze whether response to second-line biologic varies depending on reason for discontinuation of 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 8 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 to patients with LOR, and intolerance, through random effects meta-analysis. Results: As compared to 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]) (Figure 1). As compared to 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]) (Figure 2). 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 biologics, as compared to 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.
