Hatano Satoki, Nakao Hiro, Masuda Hiroshi, Ono Hiroshi, Kubota Mitsuru, Ishiguro Akira
Center for Postgraduate Education and Training, National Center for Child Health and Development, Tokyo, Japan.
Department of General Pediatrics and Interdisciplinary Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, Japan.
Pediatr Rheumatol Online J. 2025 May 13;23(1):49. doi: 10.1186/s12969-025-01108-0.
Infliximab (IFX) is a reliable choice of treatment for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients. Nationwide surveys in Japan demonstrated that additional treatment was still required for 20-30% of patients after IFX infusion. Additional IVIG was selected for 70% as the treatment for KD refractory to IFX. This study aimed to describe the therapeutic effect of IVIG after IFX for patients with KD refractory to IFX.
A cohort study was conducted at a single center involving patients treated with additional IVIG for KD refractory to IFX between January 2016 and March 2023 (IVIG-after-IFX group). Additionally, KD patients resistant to the initial IVIG and who received a second IVIG in 2016 were included as a comparison group (second-IVIG group). We employed descriptive statistics and survival analysis to describe their clinical course information, including the time from initiation of the treatment to resolution of fever and the appearance of coronary artery lesions (CALs).
The analysis included 27 cases in the IVIG-after-IFX group. The additional IVIG-after-IFX was initiated on a median 11 days of illness (range 8-29). The median time until fever resolution was 1.0 day in the IVIG-after-IFX group and 1.0 day in the second-IVIG group (P = 0.783, HR 1.00; 95% CI 0.58-1.70). The fever resolved within 2.0 days after the initiation of the therapy in 78% (21/27) in the IVIG-after-IFX group and 68% (26/38) in the second-IVIG group. CALs were identified in 26% (7/27) before initiating IVIG-after-IFX, and 7% (2/27) showed new CALs after IVIG after IFX. Persistent CALs were observed in 19% (5/27) after 12 months after diagnosis.
Additional IVIG for IFX-refractory KD may have a therapeutic effect comparable to that of the second IVIG for IVIG-resistant KD and be a hopeful therapeutic option for IFX-refractory KD. Treatment of IFX-refractory KD remains a challenge for us and requires further exploration, particularly regarding CAL prevention.
英夫利昔单抗（IFX）是治疗静脉注射免疫球蛋白（IVIG）抵抗型川崎病（KD）患者的可靠选择。日本的全国性调查表明，IFX输注后仍有20%-30%的患者需要额外治疗。70%的患者选择再次静脉注射免疫球蛋白（IVIG）作为对IFX难治性KD的治疗方法。本研究旨在描述IFX难治性KD患者接受IFX治疗后IVIG的治疗效果。
在一个中心进行了一项队列研究，纳入2016年1月至2023年3月期间接受额外IVIG治疗的IFX难治性KD患者（IFX后IVIG组）。此外，将2016年对初始IVIG耐药并接受第二次IVIG治疗的KD患者纳入作为对照组（第二次IVIG组）。我们采用描述性统计和生存分析来描述他们的临床病程信息，包括从开始治疗到发热消退和冠状动脉病变（CALs）出现的时间。
IFX后IVIG组分析包括27例患者。IFX后额外的IVIG治疗在疾病中位11天（范围8-29天）开始。IFX后IVIG组发热消退的中位时间为1.0天，第二次IVIG组为1.0天（P = 0.783，HR 1.00；95% CI 0.58-1.70）。IFX后IVIG组78%（21/27）的患者在治疗开始后2.0天内发热消退，第二次IVIG组为68%（26/38）。在开始IFX后IVIG治疗前，26%（7/27）的患者发现有CALs，IFX后IVIG治疗后7%（2/27）的患者出现新的CALs。诊断后12个月时，19%（5/27）的患者观察到持续性CALs。
IFX难治性KD的额外IVIG治疗效果可能与IVIG抵抗型KD的第二次IVIG治疗效果相当，是IFX难治性KD的一种有希望的治疗选择。IFX难治性KD的治疗对我们来说仍然是一个挑战，需要进一步探索，特别是在预防CALs方面。
