Armstrong April W, Alexis Andrew F, Blauvelt Andrew, Silverberg Jonathan I, Feeney Claire, Levenberg Mark, Chan Gary, Zhang Fan, Fostvedt Luke
Department of Dermatology, University of California Los Angeles, Los Angeles, CA, USA.
Department of Dermatology, Weill Cornell Medical College, New York, NY, USA.
Dermatol Ther (Heidelb). 2024 Jul;14(7):1849-1861. doi: 10.1007/s13555-024-01183-3. Epub 2024 Jun 19.
Early prediction of abrocitinib efficacy in atopic dermatitis (AD) could help identify candidates for an early dose increase. A predictive model determined week 12 efficacy based on week 4 responses in patients receiving abrocitinib 100 mg/day and assessed the effect of an abrocitinib dose increase on platelet counts.
Analysis included the phase 3 trials JADE MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470), and TEEN (NCT03796676). For platelet counts and simulations, a phase 2 psoriasis trial (NCT02201524) and phase 2b (NCT02780167) and phase 3 (MONO-1, MONO-2, and REGIMEN (NCT03627767)) abrocitinib trials were pooled. A training-and-validation framework assessed potential predictors of response at week 4: score and score change from baseline in the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), and Peak Pruritus Numerical Rating Scale (PP-NRS), and percentage change from baseline in EASI. The dependent variables at week 12 were ≥ 75% improvement in EASI (EASI-75) and IGA score of 0 (clear) or 1 (almost clear) and ≥ 2-point improvement from baseline. The probability of each variable to predict week 12 EASI-75 and IGA responses was calculated.
In the training cohort (n = 453), 72% of the ≥ 50% improvement in EASI (EASI-50) at week 4 responders and 16% of the nonresponders with abrocitinib 100 mg achieved EASI-75 at week 12; 48% and 6% of the week 4 EASI-50 responders and nonresponders, respectively, achieved week 12 IGA response. Similar results occurred with week 4 IGA = 2, ≥ 4-point improvement from baseline in PP-NRS, or EASI = 8 responders/nonresponders. Platelet counts after an abrocitinib dose increase from 100 to 200 mg were similar to those seen with continuous dosing with abrocitinib 100 mg or 200 mg.
Achieving week 4 clinical responses with abrocitinib 100 mg may be useful in predicting week 12 responses. Week 4 nonresponders may benefit from a dose increase to abrocitinib 200 mg, and those that receive this dose increase are likely to achieve treatment success at week 12, with no significant impact on platelet count recovery. Video abstract available for this article.
NCT03349060, NCT03575871, NCT03720470, NCT03796676, NCT02201524, NCT02780167 and NCT03627767.
早期预测阿布昔替尼治疗特应性皮炎（AD）的疗效有助于确定早期增加剂量的候选患者。一个预测模型根据接受每日100mg阿布昔替尼治疗的患者第4周的反应来确定第12周的疗效，并评估了增加阿布昔替尼剂量对血小板计数的影响。
分析纳入了3期试验JADE MONO-1（NCT03349060）、MONO-2（NCT03575871）、COMPARE（NCT03720470）和TEEN（NCT03796676）。对于血小板计数和模拟分析，汇总了一项2期银屑病试验（NCT02201524）以及2b期（NCT02780167）和3期（MONO-1、MONO-2和REGIMEN（NCT03627767））阿布昔替尼试验的数据。一个训练和验证框架评估了第4周反应的潜在预测因素：湿疹面积和严重程度指数（EASI）、研究者整体评估（IGA）以及瘙痒峰值数字评定量表（PP-NRS）从基线的评分和评分变化，以及EASI相对于基线的变化百分比。第12周的因变量为EASI改善≥75%（EASI-75）、IGA评分为0（清除）或1（几乎清除）以及相对于基线改善≥2分。计算每个变量预测第12周EASI-75和IGA反应的概率。
在训练队列（n = 453）中，第4周时EASI改善≥50%（EASI-50）的应答者中，72%在第12周实现了EASI-75，而接受100mg阿布昔替尼治疗的无应答者中这一比例为16%；第4周EASI-50应答者和无应答者中，分别有48%和6%在第12周实现了IGA反应。第4周IGA = 2、PP-NRS相对于基线改善≥4分或EASI = 8的应答者/无应答者也出现了类似结果。将阿布昔替尼剂量从100mg增加到200mg后的血小板计数与持续服用100mg或200mg阿布昔替尼时的血小板计数相似。
服用100mg阿布昔替尼在第4周实现临床反应可能有助于预测第12周的反应。第4周的无应答者可能从将剂量增加到200mg阿布昔替尼中获益，接受剂量增加的患者在第12周可能实现治疗成功，且对血小板计数恢复无显著影响。本文提供视频摘要。
NCT03349060、NCT03575871、NCT03720470、NCT03796676、NCT02201524、NCT02780167和NCT03627767。
