背景:早期预测abrocitinib在特应性皮炎(AD)中的疗效可能有助于确定早期剂量增加的候选者。预测模型基于接受100mg/天的abrocitinib的患者的第4周反应确定第12周功效,并评估abrocitinib剂量增加对血小板计数的影响。
方法:分析包括JADEMONO-1(NCT03349060),MONO-2(NCT03575871),比较(NCT03720470),和TEEN(NCT03796676)。对于血小板计数和模拟,我们合并了一项2期银屑病试验(NCT02201524)和2b期试验(NCT02780167)和3期试验(MONO-1,MONO-2和REGIMEN(NCT03627767))abrocitinib.训练和验证框架评估了第4周时反应的潜在预测因素:湿疹面积和严重程度指数(EASI)相对于基线的得分和得分变化,调查员全球评估(IGA),和峰值瘙痒数字评分量表(PP-NRS),和EASI中相对于基线的百分比变化。第12周时的因变量为EASI(EASI-75)改善≥75%,IGA评分为0(清除)或1(几乎清除),并且与基线相比改善≥2分。计算每个变量预测第12周EASI-75和IGA反应的概率。
结果:在训练队列中(n=453),在第4周,有72%的EASI(EASI-50)改善≥50%,有16%的abrocitinib100mg无反应者在第12周达到EASI-75;第4周的48%和6%的EASI-50反应者和无反应者,分别,实现了第12周的IGA响应。第4周IGA=2,PP-NRS从基线改善≥4点,或EASI=8响应者/非响应者。abrocitinib剂量从100mg增加到200mg后的血小板计数与连续给药100mg或200mgabrocitinib时的血小板计数相似。
结论:使用100mgabrocitinib实现第4周的临床反应可能有助于预测第12周的反应。第4周无应答者可能会从增加200mgabrocitinib的剂量中受益,接受这种剂量增加的患者可能在第12周获得治疗成功,对血小板计数恢复没有显著影响.本文提供的视频摘要。
背景:NCT03349060、NCT03575871、NCT03720470、NCT03796676、NCT02201524、NCT02780167和NCT03627767。
Agrocitinib是一种被批准用于中度或重度特应性皮炎患者的治疗方法。阿布西替尼片剂有两种剂量(100和200mg),每天口服一次。一些服用abrocitinib100mg的特应性皮炎患者可能需要将剂量增加到200mg以获得足够的症状缓解。我们研究了特应性皮炎患者在服用abrocitinib100mg治疗4周后是否有皮肤或瘙痒缓解或没有缓解的情况,在治疗12周后是否有可能缓解。我们还定义了治疗4周后的反应水平,可以最好地区分有或没有症状缓解的人,我们确定了谁可能受益于将abrocitinib剂量从100mg增加到200mg.我们发现,特应性皮炎患者在接受abrocitinib100mg治疗4周后症状缓解,12周后症状缓解的可能性更大。4周后未达到症状缓解的患者可从第4周的剂量增加中获益.一些接受200毫克abrocitinib的人在第4周可能会暂时减少称为血小板的某些血细胞数量,但血小板在第12周恢复到接近正常水平。该分析表明,在第4周将abrocitinib剂量从100增加到200mg似乎不会影响第4周后的血小板数量。视频摘要(MP4174529KB)。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: NCT03349060, NCT03575871, NCT03720470, NCT03796676, NCT02201524, NCT02780167 and NCT03627767.
Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis. Abrocitinib tablets are available in two doses (100 and 200 mg) and are taken by mouth once daily. Some people with atopic dermatitis who are taking abrocitinib 100 mg may need to increase the dose to 200 mg to get adequate symptom relief. We studied whether people with atopic dermatitis who did or did not experience clear skin or itch relief after taking abrocitinib 100 mg for 4 weeks are likely or not likely to experience relief after 12 weeks of treatment. We also defined the level of response after 4 weeks of treatment that best differentiates people who did or did not experience symptom relief, and we identified who might benefit from increasing the abrocitinib dose from 100 to 200 mg. We found that people with atopic dermatitis who had symptom relief after 4 weeks of abrocitinib 100 mg treatment were much more likely to have greater relief after 12 weeks, and people who did not achieve symptom relief after 4 weeks may benefit from a dose increase at week 4. Some people who receive abrocitinib 200 mg may have a temporary decrease in the number of certain blood cells called platelets at week 4, but platelets return to near-normal levels by week 12. This analysis showed that increasing the abrocitinib dose from 100 to 200 mg at week 4 did not seem to affect the platelet numbers after week 4. Video abstract (MP4 174529 KB).