PDF(Pubmed)
Abstract：
BACKGROUND: Lebrikizumab is a novel monoclonal antibody with established efficacy in patients with moderate-to-severe atopic dermatitis (AD) in multiple Phase 3 trials. One of the ultimate treatment goals for patients with moderate-to-severe AD is to achieve stable disease control without concern for planning future life events.
METHODS: In ADvocate1 and ADvocate2, lebrikizumab-treated patients meeting the protocol-defined response criteria at Week 16 were re-randomized 2:2:1 to receive lebrikizumab every 2 weeks (Q2W), lebrikizumab every 4 weeks (Q4W), or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. In this post hoc analysis, we evaluated the proportions of patients with no or minimal fluctuations of efficacy during the 36-week maintenance period and plotted individual patient trajectories. We defined no or minimal fluctuations as achieving and maintaining the defined endpoint (≥ 75% improvement in the Eczema Area and Severity Index [EASI 75], ≥ 90% improvement in EASI, Pruritus Numeric Rating Scale [NRS] ≥ 4-point improvement, or Pruritus NRS ≥ 3-point improvement) for ≥ 80% of the study visits. If patients used rescue medication, discontinued treatment, or transferred to the escape arm, data collected at or after the event were imputed as non-response.
RESULTS: The proportions of lebrikizumab responders who maintained EASI 75 with no or minimal fluctuations were 70.8% (lebrikizumab Q2W), 71.2% (lebrikizumab Q4W), and 60.0% (lebrikizumab withdrawal). Of the patients with baseline Pruritus NRS ≥ 4 and who achieved ≥ 4-point improvement at Week 16, 66.1% (lebrikizumab Q2W), 62.7% (lebrikizumab Q4W), and 55.2% (lebrikizumab withdrawal) maintained ≥ 4-point Pruritus NRS improvement with no or minimal fluctuations.
CONCLUSIONS: Patients who met the response criteria at Week 16 and continued treatment with lebrikizumab Q2W or Q4W demonstrated a stable response with no or minimal fluctuations of efficacy in measures of skin and itch up to Week 52.
BACKGROUND: NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).
Atopic dermatitis, also known as atopic eczema (or just eczema), is a common skin disease that causes itchy, dry skin. Patients with eczema are often unsure of when disease flares will happen, even while receiving treatment. In two global studies, ADvocate1 and ADvocate2, lebrikizumab improved the signs and symptoms of moderate-to-severe eczema after 16 weeks of treatment. Most of these patients also saw improvement up to 52 weeks. We wanted to know if patients continued to feel better between Week 16 and Week 52. Patients who responded to lebrikizumab after 16 weeks were given lebrikizumab every 2 weeks, lebrikizumab every 4 weeks, or placebo every 2 weeks. We tested how many patients experienced stable response to therapy, which we said was maintaining the same level of improvement on skin signs and itch symptoms for at least 80% of study visits from Week 16 to Week 52. In patients treated with lebrikizumab every 2 weeks or every 4 weeks, we saw that about seven of every ten patients maintained a stable response in skin improvement and about six of every ten patients maintained stable response in itch symptoms. In patients who stopped lebrikizumab therapy, six out of every ten patients maintained a stable skin improvement and more than five of every ten patients maintained a stable improvement in itch symptoms. In ADvocate1 and ADvocate2, most lebrikizumab-treated patients showed a stable response over time on skin and itch with dosing every 2 weeks or every 4 weeks.
METHODS: In ADvocate1 and ADvocate2, lebrikizumab-treated patients meeting the protocol-defined response criteria at Week 16 were re-randomized 2:2:1 to receive lebrikizumab every 2 weeks (Q2W), lebrikizumab every 4 weeks (Q4W), or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. In this post hoc analysis, we evaluated the proportions of patients with no or minimal fluctuations of efficacy during the 36-week maintenance period and plotted individual patient trajectories. We defined no or minimal fluctuations as achieving and maintaining the defined endpoint (≥ 75% improvement in the Eczema Area and Severity Index [EASI 75], ≥ 90% improvement in EASI, Pruritus Numeric Rating Scale [NRS] ≥ 4-point improvement, or Pruritus NRS ≥ 3-point improvement) for ≥ 80% of the study visits. If patients used rescue medication, discontinued treatment, or transferred to the escape arm, data collected at or after the event were imputed as non-response.
RESULTS: The proportions of lebrikizumab responders who maintained EASI 75 with no or minimal fluctuations were 70.8% (lebrikizumab Q2W), 71.2% (lebrikizumab Q4W), and 60.0% (lebrikizumab withdrawal). Of the patients with baseline Pruritus NRS ≥ 4 and who achieved ≥ 4-point improvement at Week 16, 66.1% (lebrikizumab Q2W), 62.7% (lebrikizumab Q4W), and 55.2% (lebrikizumab withdrawal) maintained ≥ 4-point Pruritus NRS improvement with no or minimal fluctuations.
CONCLUSIONS: Patients who met the response criteria at Week 16 and continued treatment with lebrikizumab Q2W or Q4W demonstrated a stable response with no or minimal fluctuations of efficacy in measures of skin and itch up to Week 52.
BACKGROUND: NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).
Atopic dermatitis, also known as atopic eczema (or just eczema), is a common skin disease that causes itchy, dry skin. Patients with eczema are often unsure of when disease flares will happen, even while receiving treatment. In two global studies, ADvocate1 and ADvocate2, lebrikizumab improved the signs and symptoms of moderate-to-severe eczema after 16 weeks of treatment. Most of these patients also saw improvement up to 52 weeks. We wanted to know if patients continued to feel better between Week 16 and Week 52. Patients who responded to lebrikizumab after 16 weeks were given lebrikizumab every 2 weeks, lebrikizumab every 4 weeks, or placebo every 2 weeks. We tested how many patients experienced stable response to therapy, which we said was maintaining the same level of improvement on skin signs and itch symptoms for at least 80% of study visits from Week 16 to Week 52. In patients treated with lebrikizumab every 2 weeks or every 4 weeks, we saw that about seven of every ten patients maintained a stable response in skin improvement and about six of every ten patients maintained stable response in itch symptoms. In patients who stopped lebrikizumab therapy, six out of every ten patients maintained a stable skin improvement and more than five of every ten patients maintained a stable improvement in itch symptoms. In ADvocate1 and ADvocate2, most lebrikizumab-treated patients showed a stable response over time on skin and itch with dosing every 2 weeks or every 4 weeks.
摘要：
背景：Lebrikizumab是一种新型单克隆抗体，在多个3期临床试验中对中度至重度特应性皮炎（AD）患者具有既定疗效。中度至重度AD患者的最终治疗目标之一是实现稳定的疾病控制，而无需考虑计划未来的生活事件。
方法：在ADvocate1和ADvocate2中，在第16周时符合方案定义的反应标准的lebrikizumab治疗的患者被2：2：1重新随机化，每2周（Q2W）接受lebrikizumab，lebrikizumab每4周（Q4W），或安慰剂Q2W（lebrikizumab停药）再治疗36周。在这个事后分析中，我们评估了36周维持期内疗效无波动或波动幅度最小的患者比例,并绘制了个体患者轨迹.我们将无波动或波动最小定义为达到并维持定义的终点（湿疹面积和严重程度指数[EASI75]改善≥75%，EASI改善≥90%，瘙痒数字评定量表[NRS]≥4点改善，或瘙痒NRS≥3点改善)≥80%的研究访视。如果患者使用救护药物，停止治疗，或者转移到逃生臂，在事件发生时或之后收集的数据被认为是无应答.
结果：保持EASI75无波动或波动最小的lebrikizumab应答者的比例为70.8%（lebrikizumabQ2W），71.2%（lebrikizumabQ4W），和60.0%（lebrikizumab停药）。在基线瘙痒NRS≥4且在第16周达到≥4点改善的患者中，66.1％（lebrikizumabQ2W），62.7%（lebrikizumabQ4W），55.2%(lebrikizumab停药)患者瘙痒NRS改善≥4点,无波动或波动最小.
结论：在第16周符合反应标准并继续使用lebrikizumabQ2W或Q4W治疗的患者表现出稳定的反应，直到第52周，皮肤和瘙痒的测量没有或最小的疗效波动。
背景：NCT04146363（ADvocate1）和NCT04178967（ADvocate2）。
特应性皮炎，也被称为特应性湿疹（或只是湿疹），是一种常见的皮肤病，会导致瘙痒，皮肤干燥。湿疹患者通常不确定何时会发生疾病发作，即使在接受治疗的时候。在两项全球研究中，ADvocate1和ADvocate2，lebrikizumab在治疗16周后改善了中度至重度湿疹的体征和症状。这些患者中的大多数也出现了长达52周的改善。我们想知道患者在第16周和第52周之间是否继续感觉更好。16周后对lebrikizumab有反应的患者每2周给予lebrikizumab，lebrikizumab每4周，或安慰剂每2周。我们测试了有多少患者对治疗有稳定的反应，我们说，在第16周至第52周的至少80％的研究访问中，皮肤体征和瘙痒症状的改善保持相同水平。在每2周或每4周接受lebrikizumab治疗的患者中，我们发现，每10名患者中约有7名患者在皮肤改善方面保持稳定反应，每10名患者中约有6名患者在瘙痒症状方面保持稳定反应。在停止lebrikizumab治疗的患者中，每10名患者中有6名保持皮肤稳定改善，每10名患者中有5名以上保持瘙痒症状稳定改善。在ADvocate1和ADvocate2中，大多数接受lebrikizumab治疗的患者每2周或每4周给药，随着时间的推移对皮肤和瘙痒表现出稳定的反应。
方法：在ADvocate1和ADvocate2中，在第16周时符合方案定义的反应标准的lebrikizumab治疗的患者被2：2：1重新随机化，每2周（Q2W）接受lebrikizumab，lebrikizumab每4周（Q4W），或安慰剂Q2W（lebrikizumab停药）再治疗36周。在这个事后分析中，我们评估了36周维持期内疗效无波动或波动幅度最小的患者比例,并绘制了个体患者轨迹.我们将无波动或波动最小定义为达到并维持定义的终点（湿疹面积和严重程度指数[EASI75]改善≥75%，EASI改善≥90%，瘙痒数字评定量表[NRS]≥4点改善，或瘙痒NRS≥3点改善)≥80%的研究访视。如果患者使用救护药物，停止治疗，或者转移到逃生臂，在事件发生时或之后收集的数据被认为是无应答.
结果：保持EASI75无波动或波动最小的lebrikizumab应答者的比例为70.8%（lebrikizumabQ2W），71.2%（lebrikizumabQ4W），和60.0%（lebrikizumab停药）。在基线瘙痒NRS≥4且在第16周达到≥4点改善的患者中，66.1％（lebrikizumabQ2W），62.7%（lebrikizumabQ4W），55.2%(lebrikizumab停药)患者瘙痒NRS改善≥4点,无波动或波动最小.
结论：在第16周符合反应标准并继续使用lebrikizumabQ2W或Q4W治疗的患者表现出稳定的反应，直到第52周，皮肤和瘙痒的测量没有或最小的疗效波动。
背景：NCT04146363（ADvocate1）和NCT04178967（ADvocate2）。
特应性皮炎，也被称为特应性湿疹（或只是湿疹），是一种常见的皮肤病，会导致瘙痒，皮肤干燥。湿疹患者通常不确定何时会发生疾病发作，即使在接受治疗的时候。在两项全球研究中，ADvocate1和ADvocate2，lebrikizumab在治疗16周后改善了中度至重度湿疹的体征和症状。这些患者中的大多数也出现了长达52周的改善。我们想知道患者在第16周和第52周之间是否继续感觉更好。16周后对lebrikizumab有反应的患者每2周给予lebrikizumab，lebrikizumab每4周，或安慰剂每2周。我们测试了有多少患者对治疗有稳定的反应，我们说，在第16周至第52周的至少80％的研究访问中，皮肤体征和瘙痒症状的改善保持相同水平。在每2周或每4周接受lebrikizumab治疗的患者中，我们发现，每10名患者中约有7名患者在皮肤改善方面保持稳定反应，每10名患者中约有6名患者在瘙痒症状方面保持稳定反应。在停止lebrikizumab治疗的患者中，每10名患者中有6名保持皮肤稳定改善，每10名患者中有5名以上保持瘙痒症状稳定改善。在ADvocate1和ADvocate2中，大多数接受lebrikizumab治疗的患者每2周或每4周给药，随着时间的推移对皮肤和瘙痒表现出稳定的反应。
