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Background <p>To evaluate comparative effectiveness of methotrexate (MTX), calcineurin inhibitors (CNI), Janus kinase inhibitors (JAKi), and biologics for the first-line therapies in adult-onset Still’s disease (AOSD) in real-world settings.</p> Methods <p>Two AOSD cohorts were retrospectively analysed. First, effectiveness of first-line biological versus non-biologic modulator was validated using overlap weighting of propensity scores in the Shanghai AOSD cohort. To compare AOSD treatment strategies (MTX, CNI, JAKi, biologics), we pooled data from the Shanghai and Erlangen cohorts, emulated a target trial, and applied doubly robust weighted regression to adjust for demographic and clinical confounders. The primary outcome was sustained event-free remission over 12 and 72 weeks.</p> Results <p>124 AOSD patients were analyzed, 96 from the Shanghai and 28 from Erlangen cohort. In overlap-weighted analyses of Shanghai cohort, biologic was associated with higher sustained event-free remission and event-free state than non-biologic immune modulators (<i>P</i> = 0.0065 and <i>P</i> = 0.0096). In the pooled analysis, biologics were linked to higher likelihood of event-free state and sustained event-free remission at weeks 12 and 72 (all <i>P</i> &lt; 0.05). Pairwise comparisons confirmed the advantage of biologics over CNI (sustained event-free remission at week 72 OR 0.11, <i>p</i> = 0.001), with significant benefits over MTX (OR 0.12, <i>p</i> = 0.002) and JAKi (OR 0.14, <i>p</i> = 0.008) emerging at week 72 for sustained event-free remission, and more frequent glucocorticoid discontinuation than MTX and CNI (both <i>p</i> &lt; 0.05).</p> Conclusions <p>First-line biological treatment is associated with improved sustained event-free remission compared to non-biologic treatments, such as MTX, CNI and JAKi and associated with more favorable long-term outcomes in AOSD.</p>

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Effects of first-line biologic immunomodulation compared with non-biologic therapies in adult-onset Still’s disease: a two-center cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Ruru Guo,
  • Xuesong Liu,
  • Yixuan Li,
  • Yi Qin,
  • Xinyu Li,
  • Georg Schett,
  • Liyang Gu,
  • Jürgen Rech,
  • Liangjing Lu

摘要

Background

To evaluate comparative effectiveness of methotrexate (MTX), calcineurin inhibitors (CNI), Janus kinase inhibitors (JAKi), and biologics for the first-line therapies in adult-onset Still’s disease (AOSD) in real-world settings.

Methods

Two AOSD cohorts were retrospectively analysed. First, effectiveness of first-line biological versus non-biologic modulator was validated using overlap weighting of propensity scores in the Shanghai AOSD cohort. To compare AOSD treatment strategies (MTX, CNI, JAKi, biologics), we pooled data from the Shanghai and Erlangen cohorts, emulated a target trial, and applied doubly robust weighted regression to adjust for demographic and clinical confounders. The primary outcome was sustained event-free remission over 12 and 72 weeks.

Results

124 AOSD patients were analyzed, 96 from the Shanghai and 28 from Erlangen cohort. In overlap-weighted analyses of Shanghai cohort, biologic was associated with higher sustained event-free remission and event-free state than non-biologic immune modulators (P = 0.0065 and P = 0.0096). In the pooled analysis, biologics were linked to higher likelihood of event-free state and sustained event-free remission at weeks 12 and 72 (all P < 0.05). Pairwise comparisons confirmed the advantage of biologics over CNI (sustained event-free remission at week 72 OR 0.11, p = 0.001), with significant benefits over MTX (OR 0.12, p = 0.002) and JAKi (OR 0.14, p = 0.008) emerging at week 72 for sustained event-free remission, and more frequent glucocorticoid discontinuation than MTX and CNI (both p < 0.05).

Conclusions

First-line biological treatment is associated with improved sustained event-free remission compared to non-biologic treatments, such as MTX, CNI and JAKi and associated with more favorable long-term outcomes in AOSD.