Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program.
Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program.
复制标题
DOI：
10.1002/acr.23421
复制
发表时间：
2018-05
影响因子：
4.7
通讯作者：
Boy MG
中科院分区：
文献类型：
--
作者：
Mariette X;Chen C;Biswas P;Kwok K;Boy MG
托法替尼是一种口服JAK抑制剂，用于治疗类风湿性关节炎(RA)。我们在tofacitinib RA临床开发计划中描述了淋巴瘤事件。从19项Tofacitinib研究(2项I期研究、9项II期研究、6项III期研究和2项长期延长研究)中确定了淋巴瘤事件(截至2015年3月)。这些研究中的患者接受托法替尼1-30毫克，每天两次或20毫克，每天一次，作为单一疗法或与传统的合成抗风湿药物一起服用。计算淋巴瘤发病率(IRS；有事件的患者数量/100人年)和标准化发病率(SIRS)。描述性病例配对对照分析(1：4)用于确定淋巴瘤的潜在危险因素。共有6,194名患者接受托法替尼治疗(19,406名患者--暴露年限，中位治疗时间3.4年)。发生了19个淋巴瘤(IR 0.10[95%可信区间(95%CI)0.06-0.15])，没有观察到随着暴露时间的增加而增加。经年龄和性别调整的淋巴瘤SIR为2.62(95%可信区间为1.58-4.09)(监测、流行病学和最终结果[SEER]计划数据库)。19例淋巴瘤具有典型的类风湿性关节炎患者的临床特征。3例淋巴瘤EB病毒阳性，8例阴性，2例可疑，6例未检测。在数值上，与匹配的对照组相比，更多的淋巴瘤病例有干燥综合征的病史，并且基线时抗环瓜氨酸蛋白和类风湿因子呈阳性。淋巴瘤患者的平均皮质类固醇剂量高于对照组。在tofacitinib RA临床开发计划中，淋巴瘤发病率随着时间的推移保持稳定，患有和不患有淋巴瘤的患者的基线特征差异很小。
Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). We characterized lymphoma events in the tofacitinib RA clinical development program. Lymphoma events (up to March 2015) were identified from 19 tofacitinib studies (2 phase I, 9 phase II, 6 phase III, and 2 long‐term extension) of patients with moderate to severe RA. Patients in these studies received tofacitinib dosed at 1–30 mg twice daily or 20 mg once daily, as monotherapy or with conventional synthetic disease‐modifying antirheumatic drugs. Lymphoma incidence rates (IRs; number of patients with events/100 patient‐years) and standardized incidence ratios (SIRs) were calculated. A descriptive case–matched control analysis (1:4) was performed to identify potential risk factors for lymphoma. A total of 6,194 patients received tofacitinib (19,406 patient‐years of exposure, 3.4 years median treatment duration). Nineteen lymphomas occurred (IR 0.10 [95% confidence interval (95% CI) 0.06–0.15]), with no increase observed with time of exposure. The age‐ and sex‐adjusted SIR of lymphoma was 2.62 (95% CI 1.58–4.09) (Surveillance, Epidemiology, and End Results [SEER] program database). The clinical characteristics of the 19 lymphomas were typical for the RA population. Three lymphomas were positive for Epstein‐Barr virus, 8 were negative, 2 were equivocal, and 6 were untested. Numerically, more lymphoma cases had a history of Sjögren's syndrome and were positive for anti–cyclic citrullinated protein and rheumatoid factor at baseline versus matched controls. The mean corticosteroid dose was higher for lymphoma cases versus controls. In the tofacitinib RA clinical development program, lymphoma rates were stable over time and there were minimal differences in the baseline characteristics of patients with and without lymphoma.
登录
查看更多内容
影响因子：
27.4
作者：
Conaghan PG;Østergaard M;Bowes MA;Wu C;Fuerst T;van der Heijde D;Irazoque-Palazuelos F;Soto-Raices O;Hrycaj P;Xie Z;Zhang R;Wyman BT;Bradley JD;Soma K;Wilkinson B
通讯作者：
Wilkinson B
影响因子：
--
作者：
Fleischmann, Roy;Cutolo, Maurizio;Zwillich, Samuel H.
通讯作者：
Zwillich, Samuel H.
影响因子：
--
作者：
Kremer, Joel M.;Bloom, Bradley J.;Zwillich, Samuel H.
通讯作者：
Zwillich, Samuel H.
JAK抑制剂tofacitinib抑制类风湿关节炎中的滑膜JAK1-STAT信号传导。
影响因子：
27.4
作者：
Boyle DL;Soma K;Hodge J;Kavanaugh A;Mandel D;Mease P;Shurmur R;Singhal AK;Wei N;Rosengren S;Kaplan I;Krishnaswami S;Luo Z;Bradley J;Firestein GS
通讯作者：
Firestein GS
影响因子：
158.5
作者：
Lee, Eun Bong;Fleischmann, Roy;van Vollenhoven, Ronald F.
通讯作者：
van Vollenhoven, Ronald F.