Gooderham Melinda J, Girolomoni Giampiero, Moore Julian O, Silverberg Jonathan I, Bissonnette Robert, Forman Seth, Peeva Elena, Biswas Pinaki, Valdez Hernan, Chan Gary
SKiN Centre for Dermatology, Peterborough, ON, Canada.
Università di Verona, Verona, Italy.
Dermatol Ther (Heidelb). 2022 Sep;12(9):2077-2085. doi: 10.1007/s13555-022-00764-4. Epub 2022 Aug 7.
Multiple clinical trials showed that 12 weeks of abrocitinib monotherapy was safe and effective for the treatment of moderate-to-severe atopic dermatitis (AD). The reversibility of pharmacologic activity after abrocitinib discontinuation was not described.
This post hoc analysis used data from a phase 2b study to evaluate maintenance of disease control during a 4-week drug-free follow-up period in patients with moderate-to-severe AD treated with once-daily abrocitinib (200 mg/100 mg) or placebo for 12 weeks. Proportions of patients who achieved and maintained 50% or 75% improvement in Eczema Area and Severity Index (EASI-50/EASI-75), an Investigator's Global Assessment (IGA) score of 0/1, or at least a 4-point improvement in the pruritus numeric rating scale (pruritus NRS4) were determined. Biomarkers of Janus kinase inhibition and AD disease were measured in blood samples.
Among week 12 responders to abrocitinib 200 mg, 77.4%, 42.3%, 21.1%, and 42.9% maintained their EASI-50, EASI-75, IGA, and pruritus NRS4 response at week 16; corresponding proportions of week 12 responders maintaining response to abrocitinib 100 mg were 51.9%, 35.0%, 33.3%, and 43.5%, respectively. Four weeks after abrocitinib discontinuation, all AD biomarkers reverted toward baseline levels, with high-sensitivity C-reactive protein and eosinophil percentage demonstrating the most complete recovery in patients treated with abrocitinib versus placebo.
Abrocitinib discontinuation resulted in rapid reversal of disease control consistent with reversal of suppression of pharmacodynamic and AD-specific biomarkers during the drug-free follow-up period. Maintenance of response was inversely related to the threshold of improvement. Patients with moderate-to-severe AD using continuous abrocitinib therapy would likely have the best long-term outcomes.
ClinicalTrials.gov identifier NCT02780167.
多项临床试验表明，阿博替尼单药治疗12周对中度至重度特应性皮炎（AD）的治疗是安全有效的。但未描述阿博替尼停药后药理活性的可逆性。
这项事后分析使用了一项2b期研究的数据，以评估中度至重度AD患者在接受每日一次阿博替尼（200mg/100mg）或安慰剂治疗12周后的4周无药随访期内疾病控制的维持情况。确定达到并维持湿疹面积和严重程度指数（EASI-50/EASI-75）改善50%或75%、研究者整体评估（IGA）评分为0/1或瘙痒数字评定量表（瘙痒NRS4）至少改善4分的患者比例。在血样中测量Janus激酶抑制和AD疾病的生物标志物。
在第12周对200mg阿博替尼有反应的患者中，77.4%、42.3%、21.1%和42.9%在第16周维持了他们的EASI-50、EASI-75、IGA和瘙痒NRS4反应；对100mg阿博替尼有反应的第12周患者维持反应的相应比例分别为51.9%、35.0%、33.3%和43.5%。阿博替尼停药四周后，所有AD生物标志物均恢复至基线水平，与安慰剂治疗的患者相比，高敏C反应蛋白和嗜酸性粒细胞百分比在接受阿博替尼治疗的患者中显示出最完全的恢复。
阿博替尼停药导致疾病控制迅速逆转，这与无药随访期内药效学和AD特异性生物标志物抑制的逆转一致。反应的维持与改善阈值呈负相关。使用持续阿博替尼治疗的中度至重度AD患者可能具有最佳的长期疗效。
ClinicalTrials.gov标识符NCT0278
