全身性贝伐珠单抗治疗青少年起病复发性呼吸道乳头状瘤病的疗效：个体患者数据荟萃分析

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中文摘要

目的： 青少年起病复发性呼吸道乳头状瘤病（joRRP）是一种良性但常呈侵袭性的HPV相关儿童气道疾病，常需反复手术减瘤。这些反复干预与显著发病率及生活质量受损相关，尤其是持续性发声困难。全身性贝伐珠单抗是一种抗VEGF单克隆抗体，已成为有前景的辅助治疗，但缺乏综合其跨研究疗效的个体患者水平证据。
方法： 我们进行了一项个体患者数据荟萃分析，以评估全身性贝伐珠单抗对joRRP患者手术干预率的影响。在系统检索四个电子数据库后，六项研究共33例患者符合纳入标准。30例有记录随访时长的患者纳入主要分析。使用负二项分布和对数链接的广义线性混合模型比较贝伐珠单抗开始前后的手术率，以随访时长作为偏移量。使用配对Wilcoxon符号秩检验评估Derkay评分变化。
结果： 治疗前，患者中位接受过16次手术干预（IQR 5-32）。贝伐珠单抗开始后，估计手术率从每100患者月38.6次降至1.8次，对应率比为0.047（95% CI 0.017-0.128），相对降低95.3%（P < 0.0001）。在9例有配对Derkay评分的患者中，中位评分从8（IQR 5-15）降至0（IQR 0-1；P = 0.0039）。不良事件轻微，最常见为鼻出血和蛋白尿，未报告严重不良事件。
结论： 本荟萃分析提示，全身性贝伐珠单抗可能大幅且安全地减少侵袭性joRRP儿科患者的手术负担。

英文摘要

OBJECTIVE: Juvenile-onset recurrent respiratory papillomatosis (joRRP) is a benign but often aggressive HPV-related disease of the pediatric airway, frequently requiring repeated surgical debulking. These repeated interventions are associated with substantial morbidity and impaired quality of life, particularly due to persistent dysphonia. Systemic bevacizumab, an anti-VEGF monoclonal antibody, has emerged as a promising adjuvant therapy, but individual patient-level evidence synthesizing its efficacy across studies is lacking.
METHODS: We performed an individual patient data meta-analysis to evaluate the effect of systemic bevacizumab on surgical intervention rates in patients with joRRP. Following a systematic search of four electronic databases, six studies comprising 33 patients met eligibility criteria. Thirty patients with documented follow-up duration were included in the primary analysis. Surgical rates before and after bevacizumab initiation were compared using a generalized linear mixed model with a negative binomial distribution and log link, with follow-up duration as an offset. Changes in Derkay scores were assessed using the paired Wilcoxon signed-rank test.
RESUTS: Prior to treatment, patients had undergone a median of 16 surgical interventions (IQR 5-32). The estimated surgical rate decreased from 38.6 to 1.8 procedures per 100 patient-months after bevacizumab initiation, corresponding to a rate ratio of 0.047 (95% CI 0.017-0.128) and a relative reduction of 95.3% (P < 0.0001). Among nine patients with paired Derkay scores, the median score decreased from 8 (IQR 5-15) to 0 (IQR 0-1; P = 0.0039). Adverse events were mild, most commonly epistaxis and proteinuria, with no serious adverse events reported.
CONCLUSIONS: This meta-analysis suggests that systemic bevacizumab may substantially and safely reduce surgical burden in pediatric patients with aggressive joRRP.