Supplementary Material for: Risankizumab and Certolizumab Pegol Dual-Targeted Therapy for Crohn’s Disease and Axial Spondyloarthritis: a Case Report

Introduction: Treatment of Crohn’s disease (CD) and axial spondyloarthritis (axSpA) is challenging, with CD refractory to anti-TNF antibodies. Here, we present for the first time a case treated with dual-targeted therapy (DTT) using the anti-IL-23 monoclonal risankizumab and the anti-TNF antibody certolizumab pegol.
Case Presentation: Our patient initially presented with axSpA at the age of 27. Nine years later, CD was diagnosed by the age of 36. One year after the diagnosis of CD, a spontaneous ileal perforation occurred as part of a disease course refractory to multiple anti-TNF antibodies and intolerance to immunomodulators. However, the axSpA showed a response to the anti-TNF certolizumab pegol. After stopping certolizumab pegol, we enrolled the patient into the M15-991 induction trial (MOTIVATE) and the maintenance trial (FORTIFY) testing the anti-IL-23 antibody risankizumab versus placebo in CD with failure to prior biological therapy. As a result, risankizumab induced a CD response but failed to control the axSpA. Considering the CD refractory and the axSpA responding to anti-TNFs, we initiated a DTT with risankizumab and certolizumab pegol. Risankizumab and certolizumab pegol together improved both CD and axSpA. As adverse events, there were only two episodes of spontaneously resolving common colds during the 19-month reviewed period.
Conclusion: DTT using risankizumab and certolizumab pegol is effective in CD and axSpA without serious adverse events in our patient. Combining biologicals that target specific pathways in immune-mediated diseases promises excellent potential in CD associated with extraintestinal manifestations.

引言：克罗恩病（CD）和轴向强直性脊柱炎（axSpA）的治疗颇具挑战性，尤其是CD对抗TNF抗体治疗的耐药性。本研究首次报告了一例采用双靶向治疗（DTT）治疗的患者，该治疗手段联合了抗IL-23单克隆抗体瑞赞库单抗和抗TNF抗体聚乙二醇化赛托利珠单抗。
病例报告：我们的患者在27岁时首次出现axSpA症状。九年之后，即在36岁时被诊断为CD。在CD确诊后一年，患者出现了一例自发性回肠穿孔，这是疾病进程中对多种抗TNF抗体治疗耐药并无法耐受免疫调节剂的并发症。然而，axSpA对抗TNF的赛托利珠单抗 pegol治疗产生了反应。在停止赛托利珠单抗 pegol治疗后，我们将患者纳入M15-991诱导试验（MOTIVATE）和维护试验（FORTIFY），以评估抗IL-23抗体瑞赞库单抗与安慰剂在CD中先前生物治疗失败患者中的疗效。结果，瑞赞库单抗在CD中引起了反应，但未能控制axSpA。鉴于CD的耐药性和axSpA对抗TNF的响应，我们启动了瑞赞库单抗和赛托利珠单抗 pegol的双靶向治疗。瑞赞库单抗和赛托利珠单抗 pegol的联合使用改善了CD和axSpA的症状。在19个月的观察期内，仅发生了两次自发性解除的普通感冒作为不良事件。
结论：在本次患者中，使用瑞赞库单抗和聚乙二醇化赛托利珠单抗进行双靶向治疗在CD和axSpA中表现出显著疗效，且未出现严重的不良事件。结合针对免疫介导疾病特定途径的生物制剂具有在伴有肠外表现的CD中展现出卓越潜力的巨大前景。