Geba Gregory P, Li Dateng, Xu Meng, Mohammadi Kusha, Attre Richa, Ardeleanu Marius, Musser Bret
Regeneron Pharmaceuticals, Inc, Tarrytown, NY.
Regeneron Pharmaceuticals, Inc, Tarrytown, NY.
J Allergy Clin Immunol. 2023 Mar;151(3):756-766. doi: 10.1016/j.jaci.2022.08.026. Epub 2022 Sep 7.
Atopic march refers to the sequential development of allergic diseases from infancy through adolescence, typically beginning with atopic dermatitis (AD), followed by food allergy and then airway diseases, later evolving to broader or worsened spectrum of allergic diatheses. No intervention has shown to alter its course.
We sought to determine the rate of acquisition of new or worsened allergic events for dupilumab versus placebo in patients with AD.
Allergy-associated events from 12 clinical trials were grouped into 17 allergy categories, and IgE changes from baseline were defined. A new/worsened event was considered one step of atopic march. Treatment effect was assessed by incidence rate ratios (IRRs), dupilumab versus placebo, by meta-analysis.
The duration of pooled AD studies was 4 to 52 weeks (1359 patient-years; n = 2296 dupilumab, n = 1229 placebo, median age 35 years). The median age at AD onset was 2 years. Baseline allergic disease burden was comparable between groups. Dupilumab reduced the risk of new/worsening allergies by 34% (IRR 0.66; 95% confidence interval [CI], 0.52-0.84) and new allergies by 37% (IRR 0.63; 95% CI, 0.48-0.83) versus placebo. Including IgE category shift, the IRR for combined new/worsening allergies was reduced by 54% (IRR 0.46; 95% CI, 0.36-0.57). These treatment benefits did not reverse on treatment discontinuation in off-treatment follow-up.
The acquisition/worsening of allergic conditions suggestive of atopic march was observed in a pooled adult/adolescent AD study population with inadequately controlled AD. Treatment with dupilumab reduced new/worsened allergy events versus placebo; inclusion of IgE category change increased the apparent benefit.
特应性进程是指从婴儿期到青春期过敏性疾病的相继发展，通常始于特应性皮炎（AD），随后是食物过敏，然后是气道疾病，后期演变为更广泛或更严重的过敏素质谱。尚无干预措施显示能改变其病程。
我们试图确定度普利尤单抗与安慰剂相比，AD患者出现新的或恶化的过敏事件的发生率。
将12项临床试验中与过敏相关的事件分为17类过敏，并定义了与基线相比的IgE变化。新的/恶化的事件被视为特应性进程的一个阶段。通过荟萃分析，用发病率比（IRR）评估度普利尤单抗与安慰剂相比的治疗效果。
汇总的AD研究持续时间为4至52周（1359患者年；度普利尤单抗组n = 2296，安慰剂组n = 1229，中位年龄35岁）。AD发病的中位年龄为2岁。两组之间的基线过敏性疾病负担相当。与安慰剂相比，度普利尤单抗使新的/恶化的过敏风险降低了34%（IRR 0.66；95%置信区间[CI]，0.52 - 0.84），新过敏风险降低了37%（IRR 0.63；95% CI，0.48 - 0.83）。包括IgE类别转变，新的/恶化的过敏合并发生率比降低了54%（IRR 0.46；95% CI，0.36 - 0.57）。在停药后的随访中，这些治疗益处并未因停药而逆转。
在AD控制不佳的成年/青少年AD研究汇总人群中，观察到了提示特应性进程的过敏状况的获得/恶化。与安慰剂相比，度普利尤单抗治疗减少了新的/恶化的过敏事件；纳入IgE类别变化增加了明显的益处。
