Division of Rheumatology, Immunology and Rehabilitation, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Division of Rheumatology, Medical University of Graz, Graz, Austria.
Clin Rheumatol. 2017 Oct;36(10):2187-2192. doi: 10.1007/s10067-017-3779-2. Epub 2017 Aug 3.
To analyse efficacy and safety of tocilizumab in patients with rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and/or tumour necrosis factor (TNF) inhibitors of the Swiss and Austrian patients from the ACT-SURE study. This is a sub-analysis of RA patients from Switzerland and Austria, who participated in the international phase 3b, open-label, ACT-SURE study. Patients with an inadequate response to csDMARDs or TNF antagonists receiving 8 mg/kg of IV tocilizumab every 4 weeks during a 24-week time period were included into the study. Therapy with one or more csDMARDs could be continued as combination therapy with tocilizumab (Combo) or stopped, resulting in tocilizumab monotherapy (Mono), at the treating physician's discretion. These two patient groups were analysed in separate and compared. Overall, 107 (22 on Mono vs. 85 on Combo) patients were treated with tocilizumab. The percentage of patients with at least one adverse event was significantly lower in the tocilizumab combination (58.8%) as compared to the monotherapy group (81.8%, p = 0.0458). No differences in ACR20/50/70/90 response rates were observed between both treatment groups at week 24 (Mono 63.6, 40.9, 22.7, and 18.2% vs. Combo 61.2, 43.5, 25.9, and 10.6%). The median time to low disease activity (LDA) was significantly shorter in patients treated with tocilizumab combination therapy (Mono 9.1, Combo 7.9 weeks, log rank p = 0.038). In this post hoc regional sub-analysis of the ACT-SURE study, no differences for disease activity were found comparing the two patient groups at week 24. However, median time to LDA was statistically shorter in patients treated with tocilizumab combination therapy as compared to tocilizumab monotherapy. Consequently, adding tocilizumab to csDMARD therapy rather than changing to tocilizumab monotherapy may be, in our opinion, the safest strategy to reach maximum effect in RA patients with active disease despite treatment with csDMARD. csDMARDs can be withdrawn either immediately due to adverse events or after at least low disease activity has been reached.
分析瑞士和奥地利 ACT-SURE 研究中对常规合成改善病情抗风湿药物（csDMARDs）和/或肿瘤坏死因子（TNF）抑制剂应答不足的类风湿关节炎（RA）患者使用托珠单抗的疗效和安全性。这是一项瑞士和奥地利 RA 患者的亚分析，他们参加了国际 3b 期、开放标签的 ACT-SURE 研究。在 24 周的时间内，对 csDMARDs 或 TNF 拮抗剂应答不足的患者接受 8mg/kg 的 IV 托珠单抗每 4 周一次治疗，纳入研究。可根据治疗医生的判断继续联合托珠单抗（联合治疗）或停止使用一种或多种 csDMARDs（单药治疗）。这两组患者分别进行分析并进行比较。共有 107 名（单药治疗 22 名，联合治疗 85 名）患者接受托珠单抗治疗。与单药治疗组（81.8%，p=0.0458）相比，托珠单抗联合治疗组至少发生一次不良事件的患者比例显著降低（58.8%）。在第 24 周时，两组治疗组的 ACR20/50/70/90 缓解率无差异（单药治疗组 63.6%、40.9%、22.7%和 18.2%，联合治疗组 61.2%、43.5%、25.9%和 10.6%）。接受托珠单抗联合治疗的患者达到低疾病活动度（LDA）的中位时间明显短于单药治疗组（单药治疗 9.1 周，联合治疗 7.9 周，对数秩检验 p=0.038）。在 ACT-SURE 研究的这项事后区域性亚分析中，在第 24 周时，两组患者的疾病活动度无差异。然而，与托珠单抗单药治疗相比，接受托珠单抗联合治疗的患者达到 LDA 的中位时间统计学上更短。因此，我们认为，在接受 csDMARD 治疗的活动期 RA 患者中，联合托珠单抗治疗而非改为托珠单抗单药治疗可能是达到最大疗效且最安全的策略。csDMARD 可因不良事件而立即停用，也可在至少达到低疾病活动度后停用。
