Stratification of atopic dermatitis patients by patterns of response to proactive therapy with topical tacrolimus: low serum IgE levels and inadequately controlled disease activity at the start of treatment predict its failure

Topical calcineurin inhibitors (TCIs) are an important anti-inflammatory drug for treating atopic dermatitis (AD). However, those treatment responses are variable. In this study, we stratified AD patients by patterns of response to remission maintenance therapy (proactive therapy) with topical tacrolimus, a typical TCI. Thereafter, we explored patient features that predict the success or failure of proactive therapy using TCI (TCI proactive therapy). A single-arm open-label clinical study aimed to evaluate the efficacy of TCI proactive therapy was conducted in 31 patients with AD. Patients were treated with TCS to induce remission (remission-induction period) followed by daily TCI ointment (0.1% tacrolimus) application for 4 weeks (maintenance therapy period), and twice-weekly application for 12 weeks (proactive therapy period). Based on its results, treatment outcomes were correlated with the patients’ clinical and laboratory findings. Of the 31 patients enrolled in the study, 21 successfully completed maintenance therapy (TCI responders). Among them, 13 completed (proactive-completed group) and 8 failed proactive therapy (proactive-dropout group). At the beginning of maintenance therapy, the serum IgE level was significantly higher in the TCI responders than in those who failed maintenance therapy (<i>p</i> = 0.049). At the beginning of proactive therapy, the mean-SCORing Atopic Dermatitis (SCORAD) score was significantly different between the proactive-completed (11.7 ± 4.6) and proactive-dropout (16.6 ± 4.2) groups (<i>p</i> = 0.025). In proactive-dropout group patients, worsened disease activity correlated well with the elevation of serum lactate dehydrogenase (LDH) and Thymus and activation-regulated chemokine (TARC) levels and peripheral eosinophil count. AD patients were stratified into three different response patterns to TCI proactive therapy. Patients with less involvement of IgE in the pathogenesis and inadequate remission induction by TCS may not be expected to respond well to TCI proactive therapy.Key messagesAD patients can be stratified into three types according to their pattern of responsiveness to TCI proactive therapy.The efficacy of TCI proactive therapy is lower in AD patients with lower serum IgE levels.TCI proactive therapy should be done after the achievement of adequate remission induction by TCS. AD patients can be stratified into three types according to their pattern of responsiveness to TCI proactive therapy. The efficacy of TCI proactive therapy is lower in AD patients with lower serum IgE levels. TCI proactive therapy should be done after the achievement of adequate remission induction by TCS.

外用钙调磷酸酶抑制剂（Topical calcineurin inhibitors, TCIs）是治疗特应性皮炎（atopic dermatitis, AD）的重要抗炎药物，但其临床应答存在显著个体差异。本研究以典型TCI制剂外用他克莫司为例，对AD患者接受缓解维持治疗（即主动治疗）的应答模式进行分层，随后探究可预测TCI主动治疗成败的患者特征。
本研究纳入31例AD患者，开展一项单臂开放标签临床试验以评估TCI主动治疗的疗效。所有患者先接受外用糖皮质激素（Topical Corticosteroids, TCS）诱导缓解（诱导缓解期），随后每日外用0.1%他克莫司软膏维持治疗4周（维持治疗期），再改为每周2次外用以完成12周的主动治疗阶段。基于试验结果，分析治疗转归与患者临床及实验室指标的相关性。
本研究入组的31例患者中，21例顺利完成维持治疗（TCI应答者），其中13例完成主动治疗（主动治疗完成组），8例主动治疗失败（主动治疗脱落组）。
在维持治疗起始时，TCI应答者的血清免疫球蛋白E（IgE）水平显著高于维持治疗失败者（P=0.049）。
在主动治疗起始时，主动治疗完成组（11.7±4.6）与主动治疗脱落组（16.6±4.2）的平均特应性皮炎评分（SCORAD）存在显著差异（P=0.025）。
主动治疗脱落组患者的疾病活动度恶化与血清乳酸脱氢酶（LDH）、胸腺活化调节趋化因子（TARC）水平升高及外周血嗜酸性粒细胞计数升高显著相关。AD患者可根据TCI主动治疗的应答模式分为三类。发病机制中IgE参与程度较低、且经TCS诱导缓解不充分的患者，对TCI主动治疗的应答效果通常不佳。
核心结论：
1. 可根据AD患者对TCI主动治疗的应答模式将其分为三类；
2. 血清IgE水平较低的AD患者，TCI主动治疗的疗效更差；
3. TCI主动治疗应在通过TCS实现充分诱导缓解后开展。