Sutcliffe Simon, Kalyan Shirin, Pankovich Jim, Chen Jenny M H, Gluck Rashieda, Thompson Darby, Bosiljcic Momir, Bazett Mark, Fedorak Richard N, Panaccione Remo, Axler Jeffrey, Marshall John K, Mullins David W, Kabakchiev Boyko, McGovern Dermot P B, Jang Julie, Coldman Andrew, Vandermeirsch Gillian, Bressler Brian, Gunn Hal
Qu Biologics Inc., Vancouver, BC, Canada.
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Front Med (Lausanne). 2019 Jul 19;6:170. doi: 10.3389/fmed.2019.00170. eCollection 2019.
Current Crohn's disease (CD) therapies focus on suppressing immune function and come with consequent risk, such as infection and cancer. Notwithstanding, most CD patients still experience disease progression. There is a need for new CD treatment strategies that offer better health outcomes for patients. To assess safety, efficacy, and tolerability of a novel microbial-derived immunotherapy, QBECO, that aims to restore rather than suppress immune function in CD. A randomized, double-blind, placebo-controlled trial was conducted in 68 patients with moderate-to-severe CD. Primary endpoints: safety and Week 8 clinical improvement. Secondary endpoints: Week 8 clinical response and remission. Week 8 responders continued blinded treatment through Week 16; non-responders received open-label QBECO from Weeks 9-16. Exploratory analyses included immune biomarker and genotype assessments. QBECO was well-tolerated. Mean reduction in Crohn's Disease Activity Index (CDAI) score was -68 for QBECO vs. -31 for placebo at Week 8. Improvement with QBECO continued through Week 16 (-130 CDAI reduction). Week 8 QBECO clinical response, improvement and remission rates were 41.2%, 32.4%, 29.4% vs. 26.5%, 23.5%, 23.5% for placebo. TNFα inhibitor-naïve subjects achieved higher response rates at Week 8 with QBECO (64%) vs. placebo (26%). Specific immune biomarkers were identified that linked to QBECO response. This proof-of-concept study supports further investigation for the use of QBECO as a novel immunotherapy approach for CD. Biomarker analyses suggests it may be feasible to personalize CD treatment with QBECO. Larger trials are now needed to confirm clinical improvement and the unique biological findings. NCT01809275 (https://clinicaltrials.gov/ct2/show/NCT01809275).
目前克罗恩病（CD）的治疗主要集中在抑制免疫功能，随之而来的是感染和癌症等风险。尽管如此，大多数CD患者仍经历疾病进展。需要新的CD治疗策略，为患者带来更好的健康结果。为评估一种新型微生物衍生免疫疗法QBECO的安全性、有效性和耐受性，该疗法旨在恢复而非抑制CD患者的免疫功能。对68例中重度CD患者进行了一项随机、双盲、安慰剂对照试验。主要终点：安全性和第8周的临床改善情况。次要终点：第8周的临床反应和缓解情况。第8周有反应者在第16周继续接受盲法治疗；无反应者在第9 - 16周接受开放标签的QBECO治疗。探索性分析包括免疫生物标志物和基因型评估。QBECO耐受性良好。在第8周时，QBECO组克罗恩病活动指数（CDAI）评分的平均降低值为 -68，而安慰剂组为 -31。QBECO组的改善持续到第16周（CDAI降低130）。第8周时，QBECO的临床反应、改善和缓解率分别为41.2%、32.4%、29.4%，而安慰剂组分别为26.5%、23.5%、23.5%。未使用过肿瘤坏死因子α（TNFα）抑制剂的受试者在第8周时，QBECO组的反应率更高（64%），而安慰剂组为26%。确定了与QBECO反应相关的特定免疫生物标志物。这项概念验证研究支持进一步研究将QBECO用作CD的新型免疫治疗方法。生物标志物分析表明，使用QBECO进行CD个性化治疗可能是可行的。现在需要更大规模的试验来确认临床改善情况和独特的生物学发现。NCT01809275（https://clinicaltrials.gov/ct2/show/NCT01809275）
