University Medical Center-Hamburg-Eppendorf, Hamburg, Germany.
Oregon Health & Science University, Portland, OR, USA.
Br J Dermatol. 2023 Feb 10;188(2):208-217. doi: 10.1093/bjd/ljac057.
Baricitinib, an oral, selective Janus kinase 1/2 inhibitor, demonstrated long-term efficacy in moderate-to-severe atopic dermatitis in an ongoing double-blind, phase III, long-term extension study, BREEZE-AD3 (NCT03334435).
To evaluate the efficacy and safety of downtitration and treatment withdrawal in a substudy of BREEZE-AD3.
The substudy included patients (N = 526) treated with baricitinib 4 mg or 2 mg at entry into BREEZE-AD3 who achieved a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD®) scale score of 0 (clear), 1 (almost clear) or 2 (mild) at week 52. Patients treated with baricitinib 4 mg were rerandomized to baricitinib 4 mg (continuous dosing), baricitinib 2 mg (downtitration) or placebo (treatment withdrawal, 4-mg cohort), and patients treated with baricitinib 2 mg were rerandomized to baricitinib 2 mg (continuous dosing), baricitinib 1 mg (downtitration), or placebo (treatment withdrawal, 2-mg cohort). After 16 weeks, we assessed the proportion of patients with vIGA-AD® 0/1, vIGA-AD® 0/1/2, vIGA-AD® ≥ 3 (loss of response; criterion to readminister the original baricitinib dose) and for patients who were readministered the original baricitinib dose, we assessed the proportion of patients who recaptured vIGA-AD® 0/1/2 within 16 weeks of treatment readministration (patients in the continuous dosing maintained the same dose).
For the continuous dosing, downtitration, and treatment withdrawal groups 51%, 45% and 30% of patients in the 4-mg cohort achieved vIGA-AD® 0/1 and 87%, 61% and 50% of patients achieved vIGA-AD® 0/1/2, respectively. For the 2-mg cohort, the respective proportions of patients were 48%, 42% and 25% for vIGA-AD® 0/1 and 92%, 71% and 45% for vIGA-AD® 0/1/2. The respective proportions of patients with vIGA-AD® ≥ 3 were 39%, 49% and 56% in the 4-mg cohort and 41%, 41% and 64% in the 2-mg cohort. Of those who were readministered the original baricitinib dose, the proportions of patients who recaptured vIGA-AD® 0/1/2 among the continuous dosing, downtitration, and treatment withdrawal groups were 80%, 85% and 88% in the 4-mg cohort and 90%, 56% and 86% in the 2-mg cohort, respectively.
Baricitinib allows flexibility for patients to downtitrate or stop treatment. For patients who downtitrated treatment, the majority maintained efficacy through 16 weeks. Most patients who lost efficacy with downtitration or treatment withdrawal achieved clinically relevant efficacy upon readministration of their original dose.
巴瑞替尼，一种口服、选择性 Janus 激酶 1/2 抑制剂，在一项正在进行的双盲、三期、长期扩展研究 BREEZE-AD3 中，显示出对中重度特应性皮炎的长期疗效（NCT03334435）。
评估 BREEZE-AD3 亚研究中剂量递减和治疗停药的疗效和安全性。
该亚研究纳入了 526 名在 BREEZE-AD3 入组时接受巴瑞替尼 4mg 或 2mg 治疗的患者，他们在第 52 周时达到了经验证的特应性皮炎研究者全球评估（vIGA-AD®）评分 0（清除）、1（几乎清除）或 2（轻度）。接受巴瑞替尼 4mg 治疗的患者被重新随机分配至巴瑞替尼 4mg（连续给药）、巴瑞替尼 2mg（剂量递减）或安慰剂（治疗停药，4mg 队列），接受巴瑞替尼 2mg 治疗的患者被重新随机分配至巴瑞替尼 2mg（连续给药）、巴瑞替尼 1mg（剂量递减）或安慰剂（治疗停药，2mg 队列）。16 周后，我们评估了 vIGA-AD® 0/1、vIGA-AD® 0/1/2、vIGA-AD® ≥ 3（应答丧失；重新给予原始巴瑞替尼剂量的标准）的患者比例，对于重新给予原始巴瑞替尼剂量的患者，我们评估了在重新开始治疗后 16 周内 vIGA-AD® 0/1/2 恢复的患者比例（连续给药组的患者保持相同剂量）。
在连续给药、剂量递减和治疗停药组中，4mg 队列的 51%、45%和 30%的患者达到 vIGA-AD® 0/1，87%、61%和 50%的患者达到 vIGA-AD® 0/1/2。在 2mg 队列中，分别有 48%、42%和 25%的患者达到 vIGA-AD® 0/1，92%、71%和 45%的患者达到 vIGA-AD® 0/1/2。vIGA-AD® ≥ 3 的患者比例分别为 39%、49%和 56%在 4mg 队列和 41%、41%和 64%在 2mg 队列。在重新给予原始巴瑞替尼剂量的患者中，连续给药、剂量递减和治疗停药组分别有 80%、85%和 88%的患者恢复 vIGA-AD® 0/1/2，4mg 队列和 90%、56%和 86%的患者恢复 vIGA-AD® 0/1/2在 2mg 队列中。
巴瑞替尼为患者提供了剂量递减或停药的灵活性。对于剂量递减治疗的患者，大多数患者在 16 周内保持疗效。大多数因剂量递减或停药而失去疗效的患者在重新给予原始剂量时获得了有临床意义的疗效。
