Division of Gastroenterology, University of California San Diego, La Jolla, California.
Division of Biomedical Informatics, University of California San Diego, La Jolla, California.
J Crohns Colitis. 2018 May 25;12(6):635-643. doi: 10.1093/ecco-jcc/jjy004.
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.
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.
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]).
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.
我们通过系统回顾和荟萃分析，旨在分析二线生物制剂的应答是否因停用初始抗 TNF 药物的原因（原发无应答[PNR]、初始应答后继发失应答[LOR]或不耐受）而异。
通过系统检索，我们于 2017 年 5 月 31 日之前，共确定了 8 项接受过 TNF 抑制剂治疗的 IBD 患者的生物制剂随机对照试验[RCT]，这些研究根据停止使用初始抗 TNF 治疗的原因（PNR 与 LOR 或不耐受）对二线治疗的应答进行分层。我们通过随机效应荟萃分析，估算了与 LOR 或不耐受相比，PNR 患者接受二线生物制剂治疗时达到临床缓解的相对风险[RR]（和 95%置信区间[CI]）。
与因不耐受而停止使用先前抗 TNF 药物的患者相比，先前 PNR 的患者接受二线生物制剂治疗达到缓解的可能性低 24%（RR，0.76 [0.61-0.96]）。与因 LOR 而停止使用先前抗 TNF 药物的患者相比，先前 PNR 的患者接受二线生物制剂诱导治疗达到缓解的可能性低 27%（RR，0.73 [0.56-0.97]），尤其是 ustekinumab（RR，0.64 [0.52-0.80]）。在先前对 TNF 药物有 PNR 或 LOR 的患者中，使用 vedolizumab 治疗的应答无差异（RR，1.16 [0.85-1.58]）。
与因 LOR 或不耐受而停止治疗的患者相比，抗 TNF 药物治疗的 PNR 患者对二线非 TNF 生物制剂的应答率较低。这可能归因于 PNR 患者抗 TNF 药物的药代动力学和药效动力学。
