Petit P-F, Daoudlarian D, Latifyan S, Bouchaab H, Mederos N, Doms J, Abdelhamid K, Ferahta N, Mencarelli L, Joo V, Bartolini R, Stravodimou A, Shabafrouz K, Pantaleo G, Peters S, Obeid M
Medical Oncology Service, CHU Helora, La Louvière, Belgium.
Department of Medicine, Immunology and Allergy Service.
Ann Oncol. 2025 Jan;36(1):43-53. doi: 10.1016/j.annonc.2024.08.2340. Epub 2024 Sep 5.
The aim of this retrospective study was to evaluate the dual efficacy of tocilizumab (TCZ) in the treatment of immune checkpoint inhibitor (ICI)-associated arthritis (ICI-AR) and the prevention of relapses after rechallenge.
We identified 26 patients with ICI-AR. The primary objectives were to evaluate TCZ efficacy in ICI-AR treatment and as secondary prophylaxis during ICI rechallenge in 11 of them. Patients received prednisone (CS) at 0.3 mg/kg tapered at 0.05 mg/kg weekly for six weeks. TCZ was administered at a dose of 8 mg/kg every 2 weeks. In the subgroup receiving secondary prophylaxis (rechallenge n = 11), TCZ was reintroduced with the same regimen concurrently with ICI rechallenge, and without the addition of CS. A control group of patients (rechallenge n = 5) was rechallenged without TCZ. Secondary endpoints included post-rechallenge evaluation of ICI duration, reintroduction of CS >0.1 mg/kg/day, ICI-AR flares, and disease control rate.
The median age of the patients was 70 years. The median follow-up from ICI initiation was 864 days. Among the 20 patients treated with TCZ for ICI-AR, all (100%) achieved an ACR70 response rate, defined as greater than 70% improvement, at 10 weeks. Some 81% of these patients achieved steroid-free remission after 24 weeks on TCZ. The median follow-up period was 552 days in rechallenged patients. The results demonstrated a reduction in ICI-AR relapses upon ICI rechallenge in patients receiving TCZ prophylaxis compared with patients who did not receive prophylaxis (17% versus 40%). The requirement for CS was completely abolished with prophylaxis (0% versus 20%), and the mean duration of ICI treatment was notably extended from 113 to 206 days. The 12-month post-rechallenge outcomes showed a disease control rate of 77%. During TCZ prophylaxis, CXCL9 remained elevated, showing no decline from their concentrations at the onset of ICI-AR.
In addition to treating ICI-AR, TCZ demonstrated efficacy as a secondary prophylactic agent, preventing the recurrence of symptoms and lengthening ICI treatment duration after ICI rechallenge.
本回顾性研究旨在评估托珠单抗（TCZ）在治疗免疫检查点抑制剂（ICI）相关关节炎（ICI-AR）以及预防再次使用ICI后复发方面的双重疗效。
我们纳入了26例ICI-AR患者。主要目标是评估TCZ在治疗ICI-AR以及作为11例患者再次使用ICI期间的二级预防措施时的疗效。患者接受泼尼松（CS），剂量为0.3mg/kg，每周以0.05mg/kg的剂量递减，共6周。TCZ每2周给药一次，剂量为8mg/kg。在接受二级预防的亚组（再次使用ICI的患者n = 11）中，在再次使用ICI的同时，以相同方案重新使用TCZ，且不添加CS。一组对照组患者（再次使用ICI的患者n = 5）在再次使用ICI时未使用TCZ。次要终点包括再次使用ICI后的ICI持续时间评估、重新使用CS>0.1mg/kg/天、ICI-AR复发以及疾病控制率。
患者的中位年龄为70岁。从开始使用ICI起的中位随访时间为864天。在20例接受TCZ治疗ICI-AR的患者中，所有患者（100%）在10周时达到ACR70缓解率，即改善程度大于70%。这些患者中约81%在接受TCZ治疗24周后实现无类固醇缓解。再次使用ICI的患者的中位随访期为552天。结果表明，与未接受预防的患者相比，接受TCZ预防的患者在再次使用ICI时ICI-AR复发减少（分别为17%和40%）。预防措施完全消除了对CS的需求（分别为0%和20%），并且ICI治疗的平均持续时间从113天显著延长至206天。再次使用ICI后12个月的结果显示疾病控制率为77%。在TCZ预防期间，CXCL9仍然升高，从ICI-AR开始时的浓度没有下降。
除了治疗ICI-AR外，TCZ还显示出作为二级预防药物的疗效，可预防症状复发并延长再次使用ICI后的ICI治疗持续时间。
