Search

Summary: Background: Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives: To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods: We evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results: In most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions: Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD).In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo.Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare.Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials.Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation‐regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis.Patients who responded well to dupilumab had reduced incidence of conjunctivitis.Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab‐treated patients with AD. Linked Editorial: Chia‐Yu Chu. Br J Dermatol 2019; 181:436–437. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

The Prospective Evaluation of Radial Keratotomy Study is a nine-center clinical trial of a surgical technique to reduce simple myopia by making incisions in the cornea. There were 435 patients (one eye per patient is reported) enrolled in the study with a 91% follow-up rate at 4 years after surgery. After surgery, uncorrected visual acuity was 20/40 or better in 76% of eyes. Fifty-five percent of the eyes had a refractive error within +/- 1.00 diopter; 28% were undercorrected, and 17% were overcorrected by more than 1.00 D. The width of the prediction 90% interval for the refractive change was 4.42 D, indicating a lack of predictability. The refractive error was not stable in some eyes; between 6 months and 4 years after surgery, 23% of eyes had a continued effect of the surgery of more than 1.00 D. For 323 patients with both eyes operated on, 64% stated they wore no optical correction. There were few serious complications. Eleven eyes (3%) lost two or three lines of best corrected visual acuity. Two eyes developed delayed bacterial keratitis without significant loss in best corrected visual acuity. [ABSTRACT FROM AUTHOR]

Summary: 结膜炎是一种导致眼睛变红、瘙痒和渗出的常见疾病。它在特应性皮炎(也称为湿疹)和其他过敏性疾病(包括哮喘)的患者中常见。除了过敏,感染、化学品、刺激物和其他疾病也可引起结膜炎。Dupilumab 是一种处方药,在美国批准用于不能通过局部外用(外用到皮肤)处方药控制或不能局部外用药物的≥ 12 岁中重度 AD 患者,在其他国家批准用于通过现有治疗无法控制的 AD 成人,和用于通过当前用药无法控制的≥12 岁中重度哮喘患者的维持治疗。Dupilumab 可阻滞导致这些过敏性疾病的特定物质的活性。在大部分 AD 研究中,接受dupilumab治疗患者中的结膜炎发生率多于安慰剂(模拟药物)组。为了研究这一作用,作者们评估了在 AD、哮喘、慢性鼻窦炎伴鼻息肉(CRSwNP) 和嗜酸性粒细胞性食管炎(EoE) 中开展的 11 项 dupilumab 研究中的结膜炎的发生率、风险因素、严重程度和结局。在 6 项 AD 研究的 5 项中,dupilumab治疗患者较安慰剂治疗患者更容易发生结膜炎。没有确认因感染导致的结膜炎,其性质似乎也不是过敏性的。进入这些研究时 AD 较严重患者或之前曾患过结膜炎的患者更容易患结膜炎。在哮喘和 CRSwNP 研究中,dupilumab 和安慰剂组的结膜炎发生率均低于 AD 研究,且dupilumab 和安慰剂组相似。在 EoE 研究中,没有人患有结膜炎。在所有研究中,结膜炎大部分为轻中度;大部分病例在治疗期间恢复。需要进一步研究 dupilumab治疗患者中的结膜炎原因。 Linked Article: Akinlade et al. Br J Dermatol 2019; 181:459–473 [ABSTRACT FROM AUTHOR]

Summary: Conjunctivitis is a common condition that causes the eye to become red, itchy and oozing. It is common in patients with atopic dermatitis (also called eczema), and in other allergic diseases, including asthma. Apart from allergies, conjunctivitis can also be caused by infections, chemicals, irritants, and other diseases. Dupilumab is a prescription medicine approved in the USA for people 12 years and older with moderate‐to‐severe AD uncontrolled by topical (applied to the skin) prescription medicines or who cannot use topical medicines, for adults in other countries whose AD is uncontrolled with existing therapies, and for people 12 years and older for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. Dupilumab blocks activity of specific substances that cause these allergic diseases. In most AD studies, more dupilumab‐treated patients had conjunctivitis than patients on placebo (dummy drug). To investigate this effect, the authors assessed rates, risk factors, severity, and outcomes of conjunctivitis in 11 dupilumab studies in AD, asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and eosinophilic esophagitis (EoE). In 5 of 6 AD studies, dupilumab‐treated patients were more likely to get conjunctivitis than placebo‐treated patients. No conjunctivitis was confirmed to be caused by infection, and it does not seem to be allergic in nature. Patients who entered these studies with more severe AD or who previously had conjunctivitis were more likely to get conjunctivitis. In asthma and CRSwNP studies, conjunctivitis rates were less frequent for both dupilumab and placebo than in AD studies, and were similar for dupilumab and placebo. In the EoE study, nobody had conjunctivitis. In all studies, conjunctivitis was mostly mild to moderate; most cases recovered during the treatment period. Causes of conjunctivitis in dupilumab‐treated patients require further study. Linked Article: Akinlade et al. Br J Dermatol 2019; 181:459–473 [ABSTRACT FROM AUTHOR]