Evaluation of the placebo and treatment effect overtime in randomised clinical trials evaluating the efficacy of biologics in axial spondyloarthritis: systematic review and meta-analysis.

Methods

We conducted a systematic reviewof RCTs in MEDLINE up to July 2024 (PROSPERO: CRD42024563776).

我们对截至2024年7月的MEDLINE中的随机对照试验(RCTs)进行了系统评价( PROSPERO: CRD42024563776)。

Eligible trials compared tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab, golimumab) or interleukin-17 inhibitors (bimekizumab, ixekizumab, secukinumab) versus placebo in axSpA.

符合条件的试验比较了肿瘤坏死因子抑制剂（阿达木单抗、赛妥珠单抗、依那西普、英夫利昔单抗、戈利木单抗）或白细胞介素-17抑制剂（比美克珠单抗、依克珠单抗、苏库昔单抗）与安慰剂在轴性脊柱关节炎中的效果。

Two reviewers independently selected studies and extracted data.

两位评审员独立选择研究并提取数据。

Primary outcomes were temporal trends in placebo response for Assessment of SpondyloArthritis International Society 20% and 40% response criteria (ASAS20/40), axSpA Disease Activity Score (ASDAS) Clinically Important Improvement, and ASDAS Inactive Disease (ASDAS-ID) at each trial's primary endpoint.

主要结果是评估脊柱关节炎国际协会20%和40%反应标准（ASAS20/40）、脊柱关节炎疾病活动评分（ASDAS）临床重要改善和ASDAS无活动疾病（ASDAS-ID）在每个试验的主要终点的安慰剂反应的时间趋势。

Random-effects meta-regressions estimated annual changes in treatment effects (odds ratios) and in arm-specific response rates, adjusted for age, sex, radiographic status, region, route of administration, baseline Bath Ankylosing Spondylitis Disease Activity Index score, baseline C-reactive protein, and disease duration.

随机效应的元回归估计了治疗效果（比值比）和特定于各组的反应率的年变化，对年龄、性别、放射学状态、地区、给药途径、基线巴氏强直性脊柱炎疾病活动指数评分、基线C反应蛋白和疾病持续时间进行了调整。

Results

Thirty-one RCTs (n = 6437) were included.

纳入了31项随机对照试验（n = 6437）

Treatment effect declined over time for ASAS20 (-5% per year, P < .001) and ASAS40 (-3.7%, P = .04), driven by increased placebo response (ASAS20: +1% per year, P < .0001) and a decline in treatment response for ASAS40.

治疗效果随时间下降，ASAS20每年下降5%（P < .001），ASAS40每年下降3.7%（P = .04），这一趋势由安慰剂反应增加（ASAS20：每年增加1%，P < .0001）和ASAS40治疗反应下降所驱动。

In contrast, ASDAS-based treatment effects were stable, despite a small increase in placebo ASDAS-ID (+0.19% per year, P < .05).

相比之下，基于ASDAS的治疗效果是稳定的，尽管安慰剂组ASDAS-ID略有增加（每年+0.19%，P<.05）。

Conclusions

ASAS20/40 treatment effects have declined over time in axSpA trials, consistent with a fading of reported effectiveness, whereas ASDAS-based endpoints remain stable, indicating greater robustness to placebo effects and temporal trends.

在轴性脊柱关节炎试验中，ASAS20/40治疗效果随时间下降，这与报告的有效性减弱一致，而基于ASDAS的终点保持稳定，表明其对安慰剂效应和时间趋势具有更大的稳健性。