Ciaccio Christina, Goldsobel Alan B, Anagnostou Aikaterini, Beyer Kirsten, Casale Thomas B, Deschildre Antoine, Fernández-Rivas Montserrat, Hourihane Jonathan O'B, Krawiec Marta, Lieberman Jay, Scurlock Amy M, Vickery Brian P, Smith Alex, Tilles Stephen A, Adelman Daniel C, Brown Kari R
The University of Chicago, Chicago, Illinois.
Allergy and Asthma Associates of Santa Clara Valley Research Center, San Jose, California.
Ann Allergy Asthma Immunol. 2022 Dec;129(6):758-768.e4. doi: 10.1016/j.anai.2022.07.033. Epub 2022 Aug 13.
Clinical trials (PALISADE [ARC003], ARTEMIS [ARC010]) proving efficacy and safety of peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) have used double-blind, placebo-controlled food challenges (DBPCFCs) to screen for eligibility and to evaluate efficacy. In routine clinical practice, individuals with peanut allergy do not always undergo food challenges to confirm diagnosis or determine candidacy for treatment.
To describe PTAH safety and tolerability in participants selected by clinical history and peanut sensitization parameters not undergoing DBPCFCs during trials and to compare findings with previously published data.
RAMSES (ARC007) was a 6-month, phase 3, randomized, double-blind, placebo-controlled trial in children aged 4 to 17 years with physician-confirmed peanut allergy. ARC011 was the subsequent 6-month follow-on maintenance PTAH study. The primary end point for RAMSES and ARC011 was the frequency of treatment-emergent adverse events (AEs). We descriptively compared baseline characteristics and safety outcomes from RAMSES and ARC011 to participants undergoing DBPCFCs in phase 3 PALISADE and ARTEMIS trials.
In 506 patients randomized to study treatment, baseline characteristics appeared balanced among groups. Proportion of participants with at least 1 AE was 55% for PTAH vs 33.9% for placebo during initial dose escalation and 98.8% vs 94.0% during updosing, respectively. Most participants with AEs had mild or moderate events. The most common AEs were gastrointestinal. Comparisons to pooled PALISADE and ARTEMIS data revealed higher baseline median peanut-specific immunoglobulin E and skin prick test values for RAMSES participants. Safety outcomes during trial periods were comparable.
Safety data from clinically selected children with peanut allergy receiving PTAH do not seem different from those in phase 3 trials requiring DBPCFC to enter trials.
临床试验(PALISADE [ARC003]、ARTEMIS [ARC010])已证实花生(落花生)变应原粉末 - 去脂天然花生油(PTAH)的有效性和安全性,这些试验采用双盲、安慰剂对照食物激发试验(DBPCFC)来筛选合格受试者并评估疗效。在常规临床实践中,花生过敏个体并不总是接受食物激发试验以确诊或确定是否适合治疗。
描述在试验期间根据临床病史和花生致敏参数选择的未接受DBPCFC的参与者中PTAH的安全性和耐受性,并将结果与先前发表的数据进行比较。
RAMSES(ARC007)是一项为期6个月的3期随机双盲安慰剂对照试验,受试者为4至17岁经医生确诊为花生过敏的儿童。ARC011是随后为期6个月的PTAH维持随访研究。RAMSES和ARC011的主要终点是治疗期间出现的不良事件(AE)的发生率。我们对RAMSES和ARC011的基线特征和安全性结果与3期PALISADE和ARTEMIS试验中接受DBPCFC的参与者进行了描述性比较。
在随机分配接受研究治疗的506例患者中,各组基线特征似乎均衡。在初始剂量递增期间,接受PTAH治疗的参与者中至少发生1次AE的比例为55%,而接受安慰剂治疗的为33.9%;在剂量增加期间,这一比例分别为98.8%和94.0%。大多数发生AE的参与者为轻度或中度事件。最常见的AE为胃肠道事件。与PALISADE和ARTEMIS汇总数据的比较显示,RAMSES参与者的基线花生特异性免疫球蛋白E和皮肤点刺试验值中位数更高。试验期间的安全性结果具有可比性。
临床选择的接受PTAH治疗的花生过敏儿童的安全性数据似乎与3期试验中需要DBPCFC才能进入试验的儿童的数据没有差异。