Achten Roselie, Thijs Judith, van der Wal Marlot, van Luijk Chantal, van Luin Matthijs, El Amrani Mohsin, Knol Edward, Delemarre Eveline, Jager Constance den Hartog, de Graaf Marlies, Bakker Daphne, de Boer Joke, van Wijk Femke, de Bruin-Weller Marjolein
Department of Dermatology and Allergology, National Expertise Center for Atopic Dermatitis, University Medical Center Utrecht, Utrecht, The Netherlands.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Clin Transl Allergy. 2023 Jan;13(1):e12221. doi: 10.1002/clt2.12221.
The patho-mechanism of ocular surface disease (OSD) in dupilumab-treated atopic dermatitis (AD) patients remains unclear. The aim of this study is to measure dupilumab levels in tear fluid and serum, and relate these findings to the severity of OSD during dupilumab treatment in AD patients.
This prospective study included dupilumab-treated moderate-to-severe AD patients who were seen by a dermatologist and an ophthalmologist before the start of dupilumab (baseline), and after 4 and 28 weeks of dupilumab treatment. Dupilumab levels in tear fluid and serum were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Additionally, a pilot study was conducted to measure dupilumab on conjunctival epithelial cells using flow cytometry and LC-MS/MS.
At baseline, 89.6% (n = 43/48) of the patients had OSD, with 50.0% having moderate-to-severe OSD. After 28 weeks of dupilumab treatment, the median dupilumab tear fluid levels were 0.55 mg/L (IQR 0.35-1.31) and 0.29 mg/L (IQR 0.16-0.60) in patients with moderate-to-severe OSD and patients with no or mild OSD, respectively (p = 0.02). Dupilumab levels could be detected on conjunctival epithelial cells of 5 AD patients treated with dupilumab for 4 weeks.
Patients with moderate-to-severe OSD had higher dupilumab tear fluid levels compared to patients with no or mild OSD, indicating that dupilumab reaches the ocular surface. Dupilumab was also detected in conjunctival cell suspensions and was found to directly bind CD45-conjunctival epithelial cells. This suggests that AD-induced changes of the conjunctival epithelium may play a role in the development of OSD as well as increased local drug availability.
度普利尤单抗治疗特应性皮炎（AD）患者时眼表疾病（OSD）的病理机制仍不清楚。本研究的目的是测量泪液和血清中的度普利尤单抗水平，并将这些结果与AD患者接受度普利尤单抗治疗期间OSD的严重程度相关联。
这项前瞻性研究纳入了在开始度普利尤单抗治疗前（基线）以及度普利尤单抗治疗4周和28周后由皮肤科医生和眼科医生诊治的接受度普利尤单抗治疗的中重度AD患者。通过液相色谱-串联质谱法（LC-MS/MS）测量泪液和血清中的度普利尤单抗水平。此外，还进行了一项初步研究，使用流式细胞术和LC-MS/MS在结膜上皮细胞上测量度普利尤单抗。
基线时，89.6%（n = 43/48）的患者患有OSD，其中50.0%患有中重度OSD。度普利尤单抗治疗28周后，中重度OSD患者和无或轻度OSD患者的度普利尤单抗泪液水平中位数分别为0.55 mg/L（IQR 0.35 - 1.31）和0.29 mg/L（IQR 0.16 - 0.60）（p = 0.02）。在5例接受度普利尤单抗治疗4周的AD患者的结膜上皮细胞上可检测到度普利尤单抗水平。
与无或轻度OSD患者相比，中重度OSD患者的度普利尤单抗泪液水平更高，表明度普利尤单抗可到达眼表。在结膜细胞悬液中也检测到了度普利尤单抗，并且发现其可直接结合CD45 +结膜上皮细胞。这表明AD诱导的结膜上皮变化可能在OSD的发生发展以及局部药物可用性增加中起作用。
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