Obi Ogugua Ndili, Baughman Robert P, Crouser Elliott D, Julian Mark W, Locke Landon W, Chandrasekaran Abhijeeth, Ramesh Pavithra, Kinnersley Nelson, Niranjan Vis, Culver Daniel A, Sporn Peter H S
Division of Pulmonary, Critical Care, and Sleep Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
Department of Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA.
ERJ Open Res. 2025 Jan 13;11(1). doi: 10.1183/23120541.00536-2024. eCollection 2025 Jan.
In a phase 1b/2a clinical trial of efzofitimod in patients with corticosteroid-requiring pulmonary sarcoidosis, treatment resulted in dose-dependent improvement in key end-points. We undertook a analysis pooling dose arms that achieved therapeutic concentrations of efzofitimod (Therapeutic group) those that did not (Subtherapeutic group).
Peripheral blood mononuclear cells incubated with tuberculin-coated beads were exposed to varying concentrations of efzofitimod in an assay to determine concentrations that inhibited granuloma formation. In the analysis, we compared time-to-first-relapse and changes in pulmonary function after a protocolised corticosteroid taper in the Therapeutic and Subtherapeutic groups.
Efzofitimod at ≥300 nM (19 µg·mL) inhibited granuloma formation . Based on mean efzofitimod serum concentrations achieved in the phase 1b/2a study, the 3 and 5 mg·kg dose arms were pooled as the Therapeutic group, while the 1 mg·kg arm was pooled with the placebo arm as the Subtherapeutic group. Relapse rates were 54.4% and 7.7% in the Subtherapeutic group and Therapeutic group, respectively. Median time-to-first-relapse in the Subtherapeutic group was 126 days, whereas in the Therapeutic group, only one of 17 patients relapsed by the end of the 24-week study (p=0.017). Slopes analysis showed that forced vital capacity increased in the Therapeutic group, but decreased in the Subtherapeutic group, over the course of the trial (p=0.035).
Treatment with efzofitimod at therapeutic doses, as compared with a subtherapeutic dose or placebo, was associated with a lower rate of relapse as corticosteroids were tapered.
在一项针对需要使用皮质类固醇的肺结节病患者的1b/2a期临床试验中，依佐非托莫德治疗导致关键终点出现剂量依赖性改善。我们进行了一项分析，将达到依佐非托莫德治疗浓度的剂量组（治疗组）与未达到该浓度的剂量组（亚治疗组）进行汇总。
将与结核菌素包被珠孵育的外周血单核细胞在一项实验中暴露于不同浓度的依佐非托莫德，以确定抑制肉芽肿形成的浓度。在汇总分析中，我们比较了治疗组和亚治疗组在按方案逐渐减少皮质类固醇剂量后的首次复发时间和肺功能变化。
≥300 nM（19 μg·mL）的依佐非托莫德可抑制肉芽肿形成。根据1b/2a期研究中达到的依佐非托莫德平均血清浓度，3和5 mg·kg剂量组汇总为治疗组，而1 mg·kg剂量组与安慰剂组汇总为亚治疗组。亚治疗组和治疗组的复发率分别为54.4%和7.7%。亚治疗组的首次复发中位时间为126天，而在治疗组中，在24周研究结束时，17名患者中只有1人复发（p = 0.017）。斜率分析显示，在试验过程中，治疗组的用力肺活量增加，而亚治疗组则下降（p = 0.035）。
与亚治疗剂量或安慰剂相比，使用治疗剂量的依佐非托莫德治疗与在逐渐减少皮质类固醇剂量时较低的复发率相关。
