Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease.
Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease.
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DOI：
10.1136/annrheumdis-2017-212608
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发表时间：
2018-06
影响因子：
27.4
通讯作者：
Schiffrin EJ
中科院分区：
文献类型：
--
作者：
Gabay C;Fautrel B;Rech J;Spertini F;Feist E;Kötter I;Hachulla E;Morel J;Schaeverbeke T;Hamidou MA;Martin T;Hellmich B;Lamprecht P;Schulze-Koops H;Courvoisier DS;Sleight A;Schiffrin EJ
成人斯蒂尔病（AOSD）是一种罕见的全身性自身炎症性疾病，其管理主要是经验性的。这是第一个临床研究，以确定是否白细胞介素（IL）-18抑制，使用重组人IL-18结合蛋白，tadekinig阿尔法，是一种治疗选择AOSD。在这项II期、开放标签研究中，患者年龄≥18岁，尽管接受泼尼松和/或常规合成疾病缓解抗风湿药物（DMARD）治疗，但仍有活动性AOSD伴发热或C反应蛋白（CRP）水平≥10 mg/L。允许既往接受过生物学DMARD治疗。患者接受tadekinig alfa 80 mg或160 mg皮下给药，每周3次，持续12周;接受80 mg治疗但未达到早期预测缓解标准（CRP值较基线降低≥50%和发热消退）的患者将剂量上调至160 mg，持续12周。主要终点是整个研究期间不良事件（AE）的发生率。10例患者被分配接受80 mg tadekinig alfa，13例患者被分配接受160 mg剂量。记录了155起治疗后出现的AE，其中47起被认为与研究药物相关。大多数AE为轻度，并在停药后消退。发生了3起严重AE，1起可能与治疗相关（毒性视神经病变）。在第3周，接受80 mg的10例患者中有5例和接受160 mg的12例患者中有6例达到预定义的缓解标准。我们的研究结果表明，tadekinig alfa似乎具有良好的安全性特征，并与AOSD患者的早期疗效体征相关。NCT 02398435。
Adult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory disease; its management is largely empirical. This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant human IL-18 binding protein, tadekinig alfa, is a therapeutic option in AOSD. In this phase II, open-label study, patients were ≥18 years with active AOSD plus fever or C reactive protein (CRP) levels ≥10 mg/L despite treatment with prednisone and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Previous biological DMARD treatment was permitted. Patients received tadekinig alfa 80 mg or 160 mg subcutaneously three times per week for 12 weeks; those receiving 80 mg not achieving early predicted response criteria (reduction of ≥50% CRP values from baseline and fever resolution) were up-titrated to 160 mg for a further 12 weeks. The primary endpoint was the occurrence of adverse events (AEs) throughout the study. Ten patients were assigned to receive 80 mg tadekinig alfa and 13 patients to the 160 mg dose. One hundred and fifty-five treatment-emerging AEs were recorded, and 47 were considered related to the study drug. Most AEs were mild and resolved after drug discontinuation. Three serious AEs occurred, one possibly related to treatment (toxic optic neuropathy). At week 3, 5 of 10 patients receiving 80 mg and 6 of 12 patients receiving 160 mg achieved the predefined response criteria. Our results indicate that tadekinig alfa appears to have a favourable safety profile and is associated with early signs of efficacy in patients with AOSD. NCT02398435.
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影响因子：
1.6
作者：
Ortiz-Sanjuán F;Blanco R;Riancho-Zarrabeitia L;Castañeda S;Olivé A;Riveros A;Velloso-Feijoo ML;Narváez J;Jiménez-Moleón I;Maiz-Alonso O;Ordóñez C;Bernal JA;Hernández MV;Sifuentes-Giraldo WA;Gómez-Arango C;Galíndez-Agirregoikoa E;Blanco-Madrigal J;Ortiz-Santamaria V;Del Blanco-Barnusell J;De Dios JR;Moreno M;Fiter J;Riscos ML;Carreira P;Rodriguez-Valls MJ;González-Vela MC;Calvo-Río V;Loricera J;Palmou-Fontana N;Pina T;Llorca J;González-Gay MA
通讯作者：
González-Gay MA
影响因子：
158.5
作者：
De Benedetti, Fabrizio;Brunner, Hermine I.;Martini, Alberto
通讯作者：
Martini, Alberto
影响因子：
158.5
作者：
Ruperto, Nicolino;Brunner, Hermine I.;Lovell, Daniel J.
通讯作者：
Lovell, Daniel J.
影响因子：
13.3
作者：
Ortiz-Sanjuan, Francisco;Blanco, Ricardo;Gonzalez-Gay, Miguel A.
通讯作者：
Gonzalez-Gay, Miguel A.
影响因子：
3.9
作者：
Nordstrom, Dan;Knight, Ann;Pettersson, Tom
通讯作者：
Pettersson, Tom