Department of Medicine, Rheumatology and Clinical Immunology, Charité Campus Mitte, Medizinische Klinik und Poliklinik m.S. Rheumatologie und Klinische Immunologie, Charité Universitätsmedizin Berlin, Germany.
Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Klinikum der Universität München, Campus Innenstadt, Munich, Germany.
Clin Exp Rheumatol. 2019 Nov-Dec;37(6):937-945. Epub 2019 Apr 16.
To evaluate early and late responses in biological-naïve patients with rheumatoid arthritis (RA) initiating tocilizumab and early tocilizumab non-responders who switched to rituximab.
In this open-label, non-randomised phase 3 study, RA patients with inadequate response to conventional synthetic DMARDs received tocilizumab 8 mg/kg intravenously at study begin and weeks 4, 8 and 12. After evaluation at week 16, early responders (Disease Activity Score based on 28 joints-erythrocyte sedimentation rate [DAS28-ESR] <2.6) completed the study; partial responders (DAS28-ESR decrease >1.2 or DAS28-ESR ≥2.6-≤3.2) were to continue tocilizumab through week 28; non-responders (DAS28-ESR decrease ≤1.2) switched to rituximab (1000 mg, weeks 16 and 18) with safety follow-up through week 66.
Of 519 patients, 222 (42.8%) achieved early DAS28-ESR remission at week 16; 240 patients continued treatment, 213 (41.0%) received tocilizumab, and 27 (5.2%) switched to rituximab. At week 32 DAS28-ESR remission was achieved by 117/213 patients (54.9%) who continued tocilizumab and 4/27 patients (14.8%) who switched to rituximab; good EULAR response was achieved by 66.7% and 25.9% and CDAI remission by 19.2% and 14.8% of patients, respectively. Serious adverse events occurred through week 32 in 45/490 patients (9.2%) who received tocilizumab (serious infections, 2.7%) and through week 66 in 8/27 patients (29.6%) who switched to rituximab.
Early response to tocilizumab was observed in 42.8% of patients. Half of early partial responders benefitted from continuing tocilizumab. Switching non-responders to rituximab seems feasible. No new safety signals were observed in patients treated with tocilizumab or switched to rituximab.
评估生物初治类风湿关节炎（RA）患者起始托珠单抗治疗的早期和晚期应答，以及早期托珠单抗应答不足转而使用利妥昔单抗的患者的应答。
在这项开放标签、非随机 3 期研究中，对常规合成疾病修饰抗风湿药物应答不足的 RA 患者，在研究开始时和第 4、8 和 12 周给予托珠单抗 8mg/kg 静脉输注。在第 16 周评估后，早期应答者（基于 28 个关节的红细胞沉降率[DAS28-ESR]＜2.6 的疾病活动评分）完成研究；部分应答者（DAS28-ESR 下降＞1.2 或 DAS28-ESR≥2.6~3.2）继续使用托珠单抗至第 28 周；无应答者（DAS28-ESR 下降≤1.2）则在第 16 和 18 周转换为利妥昔单抗（1000mg），并在第 66 周进行安全性随访。
在 519 例患者中，222 例（42.8%）在第 16 周达到早期 DAS28-ESR 缓解；240 例患者继续治疗，213 例（41.0%）接受托珠单抗，27 例（5.2%）转换为利妥昔单抗。在第 32 周时，继续接受托珠单抗治疗的 213 例患者中有 117 例（54.9%）达到 DAS28-ESR 缓解，而转换为利妥昔单抗的 27 例患者中有 4 例（14.8%）达到缓解；继续接受托珠单抗治疗的患者中有 66.7%和 25.9%达到良好的 EULAR 应答，而转换为利妥昔单抗的患者中有 19.2%和 14.8%达到 CDAI 缓解。接受托珠单抗治疗的患者中，在第 32 周时有 45/490 例（9.2%）发生严重不良事件（严重感染，2.7%），而在第 66 周时有 8/27 例（29.6%）转换为利妥昔单抗的患者发生严重不良事件。
42.8%的患者对托珠单抗早期应答。一半的早期部分应答者继续使用托珠单抗获益。将无应答者转换为利妥昔单抗似乎是可行的。在接受托珠单抗或转换为利妥昔单抗的患者中未观察到新的安全性信号。
