12369 Faculty of Medicine, Université Laval, Québec, QC, Canada.
54473 Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada.
J Cutan Med Surg. 2021 May-Jun;25(3):315-328. doi: 10.1177/1203475420982553. Epub 2020 Dec 22.
Dupilumab, a monoclonal antibody against the common receptor of interleukin (IL)-4 and IL-13, was the first biologic therapy approved in Canada for treatment of moderate-to-severe atopic dermatitis (AD). While it is considered safe and effective, dupilumab is not universally effective and 8%-38% of patients develop conjunctivitis, while some patients develop head and neck dermatitis. Thus, new therapeutic options are warranted. While both IL-4 and IL-13 play important roles in the pathogenesis of AD, it has been recently demonstrated that IL-13 is the primary upregulated cytokine in AD skin biopsy samples. A placebo-controlled phase 2b clinical trial evaluating the efficacy and safety of lebrikizumab, an IL-13 inhibitor, in AD demonstrated that, at 16 weeks, Eczema Area and Severity Index (EASI) 75 and Investigator's Global Assessment (IGA) 0/1 were achieved by 60.6% and 44.6% of patients taking lebrikizumab at its highest dose (vs 24.3% and 15.3% of patients taking placebo, respectively). Moreover, treatment with lebrikizumab was associated with rapid improvement of pruritus and low rates of conjunctivitis (1.4%-3.8%). Another IL-13 monoclonal antibody, tralokinumab, was evaluated for safety and efficacy in moderate-to-severe AD. By week 12, among adults receiving 300 mg tralokinumab, 42.5% achieved EASI-75 and 26.7% achieved IGA 0/1 score (vs 15.5% and 11.8% in the placebo group, respectively). Both lebrikizumab and tralokinumab demonstrated acceptable safety profiles in AD (and non-AD) trials with adverse events often being comparable between treatment and control groups. Thus, IL-13 inhibitors may provide a safe and effective treatment alternative for patients with moderate-to-severe AD.
度普利尤单抗是一种针对白细胞介素(IL)-4 和 IL-13 共同受体的单克隆抗体,是加拿大批准用于治疗中重度特应性皮炎(AD)的第一种生物疗法。虽然它被认为是安全有效的,但并非对所有患者都有效,8%-38%的患者会出现结膜炎,有些患者会出现头颈部皮炎。因此,需要新的治疗选择。虽然 IL-4 和 IL-13 在 AD 的发病机制中都起着重要作用,但最近的研究表明,IL-13 是 AD 皮肤活检样本中主要上调的细胞因子。一项评估 IL-13 抑制剂 lebrikizumab 在 AD 中的疗效和安全性的安慰剂对照 2b 期临床试验表明,在 16 周时,接受 lebrikizumab 最高剂量治疗的患者中,有 60.6%和 44.6%达到 Eczema Area and Severity Index(EASI)75 和 Investigator's Global Assessment(IGA)0/1,而接受安慰剂治疗的患者分别为 24.3%和 15.3%。此外, lebrikizumab 治疗与瘙痒迅速改善和结膜炎发生率低(1.4%-3.8%)相关。另一种 IL-13 单克隆抗体 tralokinumab 也在中度至重度 AD 中进行了安全性和疗效评估。在第 12 周,接受 300mg tralokinumab 治疗的成年人中,42.5%达到 EASI-75,26.7%达到 IGA 0/1 评分(安慰剂组分别为 15.5%和 11.8%)。 lebrikizumab 和 tralokinumab 在 AD(和非 AD)试验中均表现出可接受的安全性特征,治疗组和对照组的不良事件通常相当。因此,IL-13 抑制剂可为中重度 AD 患者提供安全有效的治疗选择。