Scholarlink

Background <p>The goal of on-demand treatment for hereditary angioedema attacks is to halt attack progression to minimize morbidity and mortality. Four on-demand treatments have been approved thus far (ecallantide, icatibant, recombinant human C1 esterase inhibitor [rhC1INH], and plasma-derived C1INH). Results from the sebetralstat phase 3 KONFIDENT trial (NCT05259917) have been reported. To put these results into context without head-to-head trials, an indirect treatment comparison (ITC) was conducted to facilitate comparisons of efficacy and safety across treatment options.</p> Methods <p>Based on a systematic literature review and feasibility assessment, only the pivotal trial for intravenous rhC1INH (NCT01188564) reported necessary data for a comparable primary efficacy endpoint (time to beginning of symptom relief) to enable an ITC with oral sebetralstat. Bayesian fixed-effects network meta-analyses models were conducted to indirectly compare the efficacy and safety outcomes of sebetralstat and rhC1INH (NCT01188564, NCT00225147, NCT00262301). A matching-adjusted indirect comparison (MAIC) of efficacy was performed, adjusting for baseline attack severity and demographic characteristics.</p> Results <p>The fixed-effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300&#xa0;mg and rhC1INH 50&#xa0;IU/kg (hazard ratio [95% credible interval], 0.96 [0.42–2.15] to 1.19 [0.58–2.45]). After adjusting for baseline attack severity, the MAIC showed numerically favorable results with sebetralstat compared with rhC1INH, regardless of whether baseline demographics were matched. The fixed-effects model found no significant differences in treatment-related treatment-emergent adverse events. All sensitivity analyses returned consistent results.</p> Conclusions <p>This ITC found no significant differences in time to beginning of symptom relief and overall treatment-related treatment-emergent adverse events between sebetralstat and rhC1INH.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Indirect treatment comparison of oral sebetralstat and intravenous recombinant human C1 esterase inhibitor for on-demand treatment of hereditary angioedema attacks

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月15日

查看全文
  • H. Henry Li,
  • Emel Aygören-Pürsün,
  • Markus Magerl,
  • Timothy J. Craig,
  • Michael E. Manning,
  • Noemi Hummel,
  • Agnieszka Kopiec,
  • Shuai Fu,
  • James Morris,
  • Alice Wang,
  • Paul K. Audhya,
  • Jonathan A. Bernstein

摘要

Background

The goal of on-demand treatment for hereditary angioedema attacks is to halt attack progression to minimize morbidity and mortality. Four on-demand treatments have been approved thus far (ecallantide, icatibant, recombinant human C1 esterase inhibitor [rhC1INH], and plasma-derived C1INH). Results from the sebetralstat phase 3 KONFIDENT trial (NCT05259917) have been reported. To put these results into context without head-to-head trials, an indirect treatment comparison (ITC) was conducted to facilitate comparisons of efficacy and safety across treatment options.

Methods

Based on a systematic literature review and feasibility assessment, only the pivotal trial for intravenous rhC1INH (NCT01188564) reported necessary data for a comparable primary efficacy endpoint (time to beginning of symptom relief) to enable an ITC with oral sebetralstat. Bayesian fixed-effects network meta-analyses models were conducted to indirectly compare the efficacy and safety outcomes of sebetralstat and rhC1INH (NCT01188564, NCT00225147, NCT00262301). A matching-adjusted indirect comparison (MAIC) of efficacy was performed, adjusting for baseline attack severity and demographic characteristics.

Results

The fixed-effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300 mg and rhC1INH 50 IU/kg (hazard ratio [95% credible interval], 0.96 [0.42–2.15] to 1.19 [0.58–2.45]). After adjusting for baseline attack severity, the MAIC showed numerically favorable results with sebetralstat compared with rhC1INH, regardless of whether baseline demographics were matched. The fixed-effects model found no significant differences in treatment-related treatment-emergent adverse events. All sensitivity analyses returned consistent results.

Conclusions

This ITC found no significant differences in time to beginning of symptom relief and overall treatment-related treatment-emergent adverse events between sebetralstat and rhC1INH.