Flex-IT! Applying "Platform Trials" Methodology to Immunotherapy for Food Allergy in Research and Clinical Practice
Flex-IT! Applying "Platform Trials" Methodology to Immunotherapy for Food Allergy in Research and Clinical Practice
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DOI：
10.1016/j.jaip.2024.01.009
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发表时间：
2024-03-06
影响因子：
9.4
通讯作者：
Turner，Paul J.
中科院分区：
文献类型：
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作者：
Mack，Douglas P.;Upton，Julia;Turner，Paul J.
食物过敏的管理越来越倾向于使用过敏原免疫疗法（AIT）进行积极治疗。虽然AIT是有效的，但治疗相关的不良事件是常见的，特别是在那些过敏原特异性IgE致敏水平高的口服免疫治疗中。在临床实践中，这些不良事件不可避免地带来挑战：临床医生和患者通常面临是否改变剂量本身、给药频率和递增速度的决定，或者完全停止AIT。因此，需要灵活调整治疗方法，特别是在临床实践中，以便参与者得到“达标治疗”。例如，这可能需要给药方案的显著变化，或者甚至从一种给药途径转换为另一种给药途径以应对频繁的不良事件。我们将这种方法称为灵活的免疫疗法。然而，几乎没有证据告诉临床医生什么样的治疗变化最有可能导致治疗成功。经典的临床试验必然依赖于相对严格的剂量增加方案。为了提供优化AIT的证据基础，食物过敏社区应该采用适应性平台试验，其中“主协议”有助于更有效的评估，包括多种干预措施的长期结果。在一项临床试验中，参与者可以在不同的治疗组之间切换;可以增加或减少干预措施，而不会影响试验的完整性。为食品AIT开发平台试验最初可能成本高昂，但它们代表了大规模发展证据基础（关于治疗结果和生物标志物发现）的重要机会。此外，它们可以帮助了解纵向疾病轨迹，这些轨迹在食物过敏的临床试验中很难研究，因为证明疗效变化需要时间。最后，它们的采用将在常规临床实践中实现更大的协作和食物过敏主动管理方法的一致性。作为一个社区，我们需要与资助者和已建立的研究合作积极追求这一点，为我们的患者及其家属提供最好的结果。
There is an increasing trend in the management of food allergy toward active treatment using allergen immunotherapy (AIT). Although AIT is efficacious, treatment-related adverse events are common, particularly with oral immunotherapy in those with high levels of allergen-specific IgE sensitization. In clinical practice, these adverse events inevitably create challenges: clinicians and patients routinely face decisions whether to alter the dose itself, the frequency of dosing, and the pace of escalation, or indeed discontinue AIT altogether. Flexibility is therefore needed to adapt treatment, particularly in clinical practice, so that participants are “treated-to-target.” For example, this may entail a significant change in the dosing protocol or even switching from one route of administration to another in response to frequent adverse events. We refer to this approach as flexible immunotherapy. However, there is little evidence to inform clinicians as to what changes to treatment are most likely to result in treatment success. Classical clinical trials rely, by necessity, on relatively rigid updosing protocols. To provide an evidence base to optimize AIT, the food allergy community should adopt adaptive platform trials, where a “master protocol” facilitates more efficient evaluation, including longer-term outcomes of multiple interventions. Within a single clinical trial, participants are able to switch between different treatment arms; interventions can be added or dropped without compromising the integrity of the trial. Developing platform trials for food AIT may initially be costly, but they represent a significant opportunity to grow the evidence base (with respect to both treatment outcomes and biomarker discovery) at scale. In addition, they could help understand longitudinal disease trajectories that are difficult to study in clinical trials for food allergy due to the time needed to demonstrate changes in efficacy. Finally, their adoption would achieve greater collaboration and consistency in approaches to proactive management of food allergy in routine clinical practice. As a community, we need to actively pursue this with funders and established research collaborations to deliver the very best outcomes for our patients and their families.