■本安全性分析调查了使用ixekizumab(IXE)治疗的患者中出现的粘膜/皮肤念珠菌感染,抗白细胞介素17A单克隆抗体,在批准的适应症中:牛皮癣(PsO),银屑病关节炎(PsA),和轴向脊柱关节炎(axSpA)。
■安全性数据来自25项临床研究。发病率(IR)表示为每100名患者-年(PY),使用整个曝光时间。
■念珠菌感染的PsO患者的IR为每100PY1.9(N=6892;总PY=18025.7),PsA患者中每100PY2.0(N=1401;总PY=2247.7),axSpA患者中每100PY为1.2(N=932;总PY=2097.7)。大多数治疗引起的念珠菌感染是:(i)患者仅经历过一次(IR=1.3;IR=1.6;IR=1.0),(ii)严重程度为轻度/中度(IR=0.8/0.9;IR=1.5/0.4;IR=0.8/0.5),而不是严重(IR=0.0;IR=0.0;IR=0.0),(iii)口腔念珠菌或生殖器念珠菌(IR=0.9/0.6;IR=1.0/0.7;IR=0.4/0.6),(iv)在研究期间标记为已恢复/已解决(89.3%;93.8%;90.3%),(v)不会导致IXE停药(0.0%;0.0%;0.1%停药),(vi)局部治疗(34.7%;22.2%;11.5%)或不使用抗真菌药物(63.5%;77.8%;80.8%),而不是全身治疗(1.5%;0.0%;7.7%),(vii)通常在下次访问之前解决。
■这项综合安全性分析表明,IXE发生念珠菌感染的风险较低,在大多数情况下,批准的IXE适应症的严重程度为轻度至中度。
■补充材料的表S1中报告了临床试验及其注册号的综合列表。
Ixekizumab(IXE)是一种被批准用于治疗牛皮癣的药物,银屑病关节炎,和轴性脊柱关节炎。IXE属于阻断称为白细胞介素-17A的蛋白的一类分子。由于白细胞介素-17A参与了对真菌的防御,这类药物的临床使用有可能增加真菌感染的风险,如念珠菌感染。因此,研究人员从25项临床研究中收集了安全性数据,包括9225名IXE成人患者:6892名银屑病患者,1401患有银屑病关节炎,932患有轴向脊柱关节炎。研究人员观察了新的念珠菌感染病例的发生率,所谓的发病率,并发现在银屑病组中,每100名患者年有1.9名患者经历至少1次念珠菌感染,在银屑病关节炎组中,每100个患者年2.0个,轴性脊柱关节炎组每100例患者-年1.2例。适应症,大多数念珠菌感染(I)患者只经历过一次,(ii)严重程度为轻度或中度,(iii)涉及由口腔或生殖器浅表皮肤真菌引起的感染,(iv)在研究期间被认为已恢复/解决,(v)没有导致IXE停药,(vi)使用局部抗真菌药物或Nomedications进行管理,和(vii)通常在下次访问之前解决。总之,这项安全性分析表明,IXE感染念珠菌的风险较低,在大多数情况下,批准的IXE适应症的严重程度为轻度至中度。
UNASSIGNED: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA).
UNASSIGNED: Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure.
UNASSIGNED: Candida infections had an IR of 1.9 per 100 PY in patients with PsO (N = 6892;total PY = 18025.7), 2.0 per 100 PY in patients with PsA (N = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA (N = 932;total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit.
UNASSIGNED: This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications.
UNASSIGNED: A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material.
Ixekizumab(IXE) is a drug approved for the treatment of psoriasis, psoriatic arthritis,and axial spondyloarthritis. IXE belongs to the class of molecules that block aprotein called interleukin-17A. Since interleukin-17A is involved in the defenseagainst fungi, the clinical use of this class of drug has the potential to increasethe risk of developing fungal infections, such as Candida infections.Therefore, researcherscollected safety data from 25 clinical studies comprising 9225 adult patientstreated with IXE: 6892 with psoriasis, 1401 with psoriatic arthritis, and 932with axial spondyloarthritis. Researchers looked at the rate of new cases of Candidainfections, the so-called incidence rate, and found that 1.9 per 100patient-years experienced at least 1 Candida infection in the psoriasis group, 2.0per 100 patient-years in the psoriatic arthritis group, and 1.2 per 100patient-years in the axial spondyloarthritis group.Acrossindications, the majority of Candida infections (i) were experienced only once by patients, (ii) were mild or moderate in severity, (iii) involved infections caused by superficial skin fungus in themouth or genitals, (iv) wereconsidered recovered/resolved during the studies, (v) did not lead to IXE discontinuation, (vi) were managed with topical anti-fungal medications or nomedications, and (vii) typicallyresolved before next visit.In conclusion,this safety analysis shows that the risk of developing Candida infections islow with IXE, and the severity is mild-to-moderate in most instances across theapproved IXE indications.