Rheumatology and Clinical Immunology, UMC Utrecht, Utrecht, The Netherlands
Rheumatology and Clinical Immunology, UMC Utrecht, Utrecht, The Netherlands.
Ann Rheum Dis. 2019 Oct;78(10):1333-1338. doi: 10.1136/annrheumdis-2019-215304. Epub 2019 Jun 13.
Methotrexate (MTX), often combined with low moderately dosed prednisone, is still the cornerstone of initial treatment for early rheumatoid arthritis (RA). It is not known how this strategy compares with initial treatment with a biological. We therefore compared the effectiveness of tocilizumab (TCZ), or TCZ plus MTX (TCZ+MTX) with MTX plus 10 mg prednisone (MTX+pred), all initiated within a treat-to-target treatment strategy in early RA.
Using individual patient data of two trials, we indirectly compared tight-controlled treat-to-target strategies initiating TCZ (n=103), TCZ+MTX (n=106) or MTX+pred (n=117), using initiation of MTX (n=227) as reference. Primary outcome was Disease Activity Score assessing 28 joints (DAS28) over 24 months. To assess the influence of acute phase reactants (APRs), a disease activity composite outcome score without APR (ie, modification of the Clinical Disease Activity Index (m-CDAI)) was analysed. Secondary outcomes were remission (several definitions), physical function and radiographic progression. Multilevel models were used to account for clustering within trials and patients over time, correcting for relevant confounders.
DAS28 over 24 months was lower for TCZ+MTX than for MTX+Pred (mean difference: -0.62 (95% CI -1.14 to -0.10)). Remission was more often achieved in TCZ+MTX and in TCZ versus MTX+pred (p=0.02/0.05, respectively). Excluding APRs from the disease activity outcome score, TCZ-based strategies showed a slightly higher m-CDAI compared with MTX+pred, but this was not statistically significant. Other outcomes were also not statistically significantly different between the strategies.
In patients with early RA, although TCZ-based strategies resulted in better DAS28 and remission rates compared with MTX+pred, at least part of these effects may be due to a specific effect of TCZ on APRs.
甲氨蝶呤（MTX）常与低至中剂量泼尼松联合使用，仍是早期类风湿关节炎（RA）初始治疗的基石。目前尚不清楚这一策略与初始使用生物制剂的策略相比如何。因此，我们比较了托珠单抗（TCZ）或 TCZ+MTX（TCZ+MTX）与 MTX+10mg 泼尼松（MTX+pred）在早期 RA 患者中起始的靶向治疗策略的有效性。
利用两项试验的个体患者数据，我们以起始 MTX（n=227）为参照，间接比较了起始 TCZ（n=103）、TCZ+MTX（n=106）或 MTX+pred（n=117）的严格靶向治疗策略。主要结局是 24 个月时的 28 个关节疾病活动评分（DAS28）。为评估急性期反应物（APRs）的影响，分析了不包含 APR 的疾病活动综合评分（即临床疾病活动指数的改良评分（m-CDAI））。次要结局是缓解（几种定义）、身体功能和放射学进展。使用多级模型来解释试验内和患者随时间的聚类，并校正相关混杂因素。
与 MTX+pred 相比，TCZ+MTX 组在 24 个月时 DAS28 更低（平均差异：-0.62（95%CI -1.14 至 -0.10））。TCZ+MTX 和 TCZ 组较 MTX+pred 组更常达到缓解（p=0.02/0.05）。从疾病活动评分中排除 APRs 后，TCZ 为基础的策略与 MTX+pred 相比，m-CDAI 略高，但无统计学意义。其他结局在不同策略之间也无统计学差异。
在早期 RA 患者中，虽然与 MTX+pred 相比，TCZ 为基础的策略导致 DAS28 和缓解率更高，但这些结果至少部分可能归因于 TCZ 对 APRs 的特定作用。
