Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials.
Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials.
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DOI：
10.1136/annrheumdis-2016-210457
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发表时间：
2017-07
影响因子：
27.4
通讯作者：
Wollenhaupt J
中科院分区：
文献类型：
--
作者：
Cohen SB;Tanaka Y;Mariette X;Curtis JR;Lee EB;Nash P;Winthrop KL;Charles-Schoeman C;Thirunavukkarasu K;DeMasi R;Geier J;Kwok K;Wang L;Riese R;Wollenhaupt J
托法替尼是一种口服Janus激酶抑制剂，用于治疗类风湿性关节炎（RA）。我们报告了在成人活动性RA患者中进行的2项I期、9项II期、6项III期和2项长期扩展研究的托法替尼综合安全性总结。汇总所有托法替尼治疗患者的数据（数据截止日期：2015年3月31日）。报告了关注不良事件（AE）的发生率（IR;发生事件的患者/100患者-年）和95% CI。6194例患者接受托法替布治疗，暴露量总计为19406患者-年;中位暴露量为3.4患者-年。 严重AE的IR（95% CI）为9.4（9.0 - 9.9）;严重感染的IR为2.7（2.5 - 3.0）。（所有）带状疱疹的IR为3.9（3.6 - 4.2）;播散性或多发性带状疱疹的IR为0.3（0.2 - 0.4）。机会性感染（不包括结核病）的IR为0.3（0.2至0.4），结核病的IR为0.2（0.1至0.3）。恶性肿瘤（不包括非黑色素瘤皮肤癌（NMSC））的IR为0.9（0.8 - 1.0）; NMSC IR为0.6（0.5 - 0.7）。胃肠穿孔的IR为0.1（0.1 - 0.2）。按6个月间隔对严重感染、带状疱疹和恶性肿瘤的IR进行分析，未发现IR随托法替尼暴露持续时间延长而显著增加。这项长达8.5年的托法替尼暴露分析允许估计安全性事件，与既往托法替尼报告相比，精确度提高。 AE通常随时间推移保持稳定;与既往托法替尼报告相比，未观察到新的安全性信号。 NCT 01262118、NCT 01484561、NCT 00147498、NCT 00413660、NCT 00550446、NCT 00603512、NCT 00687193、NCT 01164579、NCT 00976599、NCT 01059864、NCT 01359150、NCT 00960440、NCT 00847613、NCT 00814307，NCT 00856544、NCT 00853385、NCT 01039688、NCT 00413699、NCT 00661661;结果。
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report an integrated safety summary of tofacitinib from two phase I, nine phase II, six phase III and two long-term extension studies in adult patients with active RA. Data were pooled for all tofacitinib-treated patients (data cut-off: 31 March 2015). Incidence rates (IRs; patients with event/100 patient-years) and 95% CIs are reported for adverse events (AEs) of interest. 6194 patients received tofacitinib for a total 19 406 patient-years' exposure; median exposure was 3.4 patient-years. IR (95% CI) for serious AEs was 9.4 (9.0 to 9.9); IR for serious infections was 2.7 (2.5 to 3.0). IR for (all) herpes zoster was 3.9 (3.6 to 4.2); IR for disseminated or multidermatomal herpes zoster was 0.3 (0.2 to 0.4). IR for opportunistic infections (excluding tuberculosis) was 0.3 (0.2 to 0.4) and was 0.2 (0.1 to 0.3) for tuberculosis. IR for malignancies (excluding non-melanoma skin cancer (NMSC)) was 0.9 (0.8 to 1.0); NMSC IR was 0.6 (0.5 to 0.7). IR for gastrointestinal perforations was 0.1 (0.1 to 0.2). Analysis of IR for serious infections, herpes zoster and malignancies by 6-month intervals did not reveal any notable increase in IR with longer-duration tofacitinib exposure. This analysis of tofacitinib exposure up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. AEs were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports. NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT00413699, NCT00661661; Results.
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影响因子：
--
作者：
Curtis, Jeffrey R.;Xie, Fenglong;Delzell, Elizabeth
通讯作者：
Delzell, Elizabeth
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.
影响因子：
13.3
作者：
Cohen, Stanley;Radominski, Sebastiao C.;Riese, Richard
通讯作者：
Riese, Richard