Kridin Khalaf, Abdelghaffar Mariam, Bieber Katja, Thaci Diamant, Ludwig Ralf J
Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel.
J Eur Acad Dermatol Venereol. 2025 May 25. doi: 10.1111/jdv.20724.
A low risk of infections was found in the randomized placebo-controlled trials of dupilumab in atopic dermatitis (AD). Dupilumab-associated real-life long-term risk of infections remains unclear.
To assess the risk of infectious complications in patients with AD managed by dupilumab relative to those treated with methotrexate and cyclosporine.
Using the TriNetX global dataset, a retrospective cohort study comprised two distinct analyses comparing patients with AD under different treatments: (i) initiators of dupilumab (n = 10,913) versus methotrexate (n = 10,913) and (ii) initiators of dupilumab (n = 6943) versus cyclosporine (n = 6943). Study groups were compared regarding the risk of 32 infections during the initial 3 years following drug initiation. Propensity score matching was conducted to optimize inter-group comparability.
During the first year of treatment, relative to methotrexate and cyclosporine, dupilumab was associated with a decreased risk of herpetic (HR, 0.59; 95% CI, 0.47-0.74 and HR, 0.65; 95% CI, 0.50-0.85, respectively) and non-herpetic skin infection (HR, 0.55; 95% CI, 0.49-0.63 and HR, 0.68; 95% CI, 0.58-0.80, respectively) and systemic infections (HR, 0.39; 95% CI, 0.34-0.44 and HR, 0.47; 95% CI, 0.40-0.56, respectively). More specifically, relative to cyclosporine, dupilumab was associated with a reduced risk of pneumonia, urinary tract infection (UTI), upper respiratory tract infection (URTI), otitis media, sinusitis, herpes simplex, herpes zoster, hepatitis B virus (HBV) and HCV reactivation, cytomegalovirus, Epstein-Barr virus, infective gastroenteritis, influenza, parasitic diseases, pneumocystis jirovecii pneumonia, cellulitis, folliculitis, mucocutaneous candidiasis and dermatophytosis. Compared to methotrexate, dupilumab conferred a decreased risk of the aforementioned infections (apart from herpes simplex and HCV reactivation) as well as septicaemia, meningitis, encephalitis, osteomyelitis and tuberculosis. The risk of eczema herpeticum was not increased among dupilumab-treated patients.
Dupilumab is associated with a reduced risk of a wide array of systemic and cutaneous infections. This agent might be preferred in patients with susceptibility to infections.
在度普利尤单抗治疗特应性皮炎（AD）的随机安慰剂对照试验中发现感染风险较低。度普利尤单抗在实际应用中的长期感染风险仍不明确。
评估接受度普利尤单抗治疗的AD患者相对于接受甲氨蝶呤和环孢素治疗的患者发生感染并发症的风险。
利用TriNetX全球数据集，进行了一项回顾性队列研究，包括两项不同的分析，比较不同治疗方案下的AD患者：（i）度普利尤单抗起始治疗者（n = 10913）与甲氨蝶呤起始治疗者（n = 10913），以及（ii）度普利尤单抗起始治疗者（n = 6943）与环孢素起始治疗者（n = 6943）。比较研究组在药物起始治疗后的最初3年内发生32种感染的风险。进行倾向评分匹配以优化组间可比性。
在治疗的第一年，相对于甲氨蝶呤和环孢素，度普利尤单抗与疱疹性感染（HR，0.59；95%CI，0.47 - 0.74和HR，0.65；95%CI，0.50 - 0.85）、非疱疹性皮肤感染（HR，0.55；95%CI，0.49 - 0.63和HR，0.68；95%CI，0.58 - 0.80）以及全身感染（HR，0.39；95%CI，0.34 - 0.44和HR，0.47；95%CI，0.40 - 0.56）的风险降低相关。更具体地说，相对于环孢素，度普利尤单抗与肺炎、尿路感染（UTI）、上呼吸道感染（URTI）、中耳炎、鼻窦炎、单纯疱疹、带状疱疹、乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）再激活、巨细胞病毒、EB病毒、感染性肠胃炎、流感、寄生虫病、耶氏肺孢子菌肺炎、蜂窝织炎、毛囊炎、黏膜皮肤念珠菌病和皮肤癣菌病的风险降低相关。与甲氨蝶呤相比，度普利尤单抗使上述感染（除单纯疱疹和HCV再激活外）以及败血症、脑膜炎、脑炎、骨髓炎和结核病的风险降低。接受度普利尤单抗治疗的患者中，疱疹样湿疹的风险并未增加。
度普利尤单抗与多种全身和皮肤感染的风险降低相关。对于易感染患者，该药物可能是更优选择。
