Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Corporal Michael J. Crescenz VAMC, Philadelphia, PA.
Department of Internal Medicine, Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Rheumatology (Oxford). 2022 May 30;61(6):2413-2423. doi: 10.1093/rheumatology/keab685.
To explore the safety and efficacy of filgotinib (FIL), a Janus kinase 1 inhibitor, and lanraplenib (LANRA), a spleen kinase inhibitor, in cutaneous lupus erythematosus (CLE).
This was a phase 2, randomized, double-blind, placebo-controlled, exploratory, proof-of-concept study of LANRA (30 mg), FIL (200 mg) or placebo (PBO) once daily for 12 weeks in patients with active CLE. At week 12, PBO patients were rerandomized 1:1 to receive LANRA or FIL for up to 36 additional weeks.
Of 47 randomized patients, 45 were treated (PBO, n = 9; LANRA, n = 19; FIL, n = 17). The primary endpoint [change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score at week 12] was not met. The least squares mean CLASI-A score change from baseline was -5.5 (s.e. 2.56) with PBO, -4.5 (1.91) with LANRA and -8.7 (1.85) with FIL. Numerical differences between FIL and PBO were greater in select subgroups. A ≥5-point improvement in the CLASI-A score at week 12 was achieved by 50.0%, 56.3% and 68.8% in the PBO, LANRA and FIL arms, respectively. A numerically greater proportion of patients in the FIL arm (50%) also achieved ≥50% improvement in the CLASI-A score at week 12 (37.5% PBO, 31.3% LANRA). Most adverse events (AEs) were mild or moderate in severity. Two serious AEs were reported with LANRA and one with FIL.
The primary endpoint was not met. Select subgroups displayed a numerically greater treatment response to FIL relative to PBO. LANRA and FIL were generally well tolerated.
ClinicalTrials.gov identifier NCT03134222.
探索 Janus 激酶 1 抑制剂 filgotinib（FIL）和脾激酶抑制剂 lanraplenib（LANRA）在红斑狼疮性皮疹中的安全性和疗效。
这是一项为期 12 周的、随机、双盲、安慰剂对照、探索性的、概念验证研究，共纳入 47 名活动性红斑狼疮性皮疹患者，接受每日一次的 LANRA（30mg）、FIL（200mg）或安慰剂（PBO）治疗。在第 12 周时，PBO 患者按 1:1 比例重新随机分组，接受 LANRA 或 FIL 治疗，最长可达 36 周。
47 名随机患者中，45 名接受了治疗（PBO，n=9；LANRA，n=19；FIL，n=17）。主要终点（12 周时从基线的 Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity [CLASI-A] 评分变化）未达到。最小二乘均数 CLASI-A 评分从基线的变化分别为 PBO 组-5.5（s.e. 2.56），LANRA 组-4.5（1.91），FIL 组-8.7（1.85）。在某些亚组中，FIL 与 PBO 之间的差异具有数值意义。在第 12 周时，CLASI-A 评分改善≥5 分的患者比例分别为 50.0%、56.3%和 68.8%，PBO、LANRA 和 FIL 组分别为 50.0%、56.3%和 68.8%。在第 12 周时，FIL 组中还有更多的患者（50%）达到 CLASI-A 评分改善≥50%（PBO 组为 37.5%，LANRA 组为 31.3%）。大多数不良事件（AE）的严重程度为轻度或中度。报告了 2 例与 LANRA 相关的严重不良事件和 1 例与 FIL 相关的严重不良事件。
主要终点未达到。某些亚组患者对 FIL 的治疗反应较 PBO 更具有数值意义。LANRA 和 FIL 通常具有良好的耐受性。
ClinicalTrials.gov 标识符 NCT03134222。
