托法替布治疗强直性脊柱炎2期和3期试验的综合安全性分析
Integrated safety analysis of tofacitinib from Phase 2 and 3 trials of patients with ankylosing spondylitis.
作者信息
Deodhar Atul, Akar Servet, Curtis Jeffrey R, El-Zorkany Bassel, Magrey Marina, Wang Cunshan, Wu Joseph, Makgoeng Solomon B, Vranic Ivana, Menon Sujatha, Fleishaker Dona L, Diehl Annette M, Fallon Lara, Yndestad Arne, Landewé Robert B M
机构信息
Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239-3098, USA.
Faculty of Medicine, Division of Rheumatology, Department of Internal Medicine, Izmir Kâtip Çelebi University, Izmir, Turkey.
出版信息
Adv Rheumatol. 2024 Dec 18;64(1):87. doi: 10.1186/s42358-024-00402-x.
OBJECTIVES
Describe tofacitinib safety from an integrated analysis of randomized controlled trials (RCTs) in patients with ankylosing spondylitis (AS).
METHOD
Pooled data from Phase 2 (NCT01786668; 04/2013-03/2015)/Phase 3 (NCT03502616; 06/2018-08/2020) RCTs in AS patients were analyzed (3 overlapping cohorts): 16-week placebo-controlled (tofacitinib 5 mg twice daily [BID] [n = 185]; placebo [n = 187]); 48-week only-tofacitinib 5 mg BID (n = 316); 48-week all-tofacitinib (≥ 1 dose of tofacitinib 2, 5, or 10 mg BID; n = 420). Baseline 10-year atherosclerotic cardiovascular disease (ASCVD) risk was determined in patients without history of ASCVD (48-week cohorts). Adverse events (AEs)/AEs of special interest were evaluated/compared with findings from other tofacitinib programs (16 Phase 2/Phase 3 rheumatoid arthritis [RA]; 2 Phase 3 psoriatic arthritis [PsA] RCTs) and a real-world cohort of AS patients initiating biologic disease-modifying antirheumatic drugs (US MarketScan).
RESULTS
Most patients (> 75%; 48-week cohorts) without history of ASCVD had low baseline 10-year ASCVD risk. One patient (tofacitinib 5 mg BID; in all 3 cohorts) had a serious infection (aseptic meningitis). Herpes zoster (non-serious) occurred in the 48-week only-tofacitinib 5 mg BID (n = 5 [1.6%]) and all-tofacitinib (n = 7 [1.7%]; one multi-dermatomal [tofacitinib 10 mg BID]) cohorts. No deaths, opportunistic infections, tuberculosis, malignancies, major adverse cardiovascular events, thromboembolic events, gastrointestinal perforations occurred.
LIMITATIONS
short RCT durations/low patient numbers within cohorts.
CONCLUSION
Tofacitinib 5 mg BID was well tolerated to 48 weeks in AS patients; safety profile was consistent with RA/PsA clinical programs and a cohort of AS patients from US routine clinical practice.
CLINICAL TRIAL REGISTRATION NUMBERS
NCT01786668 (2013-02-06); NCT03502616 (2018-04-11).
目的
通过对强直性脊柱炎（AS）患者随机对照试验（RCT）的综合分析来描述托法替布的安全性。
方法
分析来自AS患者的2期（NCT01786668；2013年4月 - 2015年3月）/3期（NCT03502616；2018年6月 - 2020年8月）RCT的汇总数据（3个重叠队列）：16周安慰剂对照试验（托法替布5毫克每日两次 [BID] [n = 185]；安慰剂 [n = 187]）；48周仅使用托法替布5毫克BID（n = 316）；48周使用所有剂量托法替布（≥1剂托法替布2、5或10毫克BID；n = 420）。在无动脉粥样硬化性心血管疾病（ASCVD）病史的患者（48周队列）中确定基线10年ASCVD风险。评估特殊关注的不良事件（AE）/AE，并与其他托法替布研究项目（16项2期/3期类风湿关节炎 [RA]；2项3期银屑病关节炎 [PsA] RCT）以及一组开始使用生物疾病改善抗风湿药物的AS患者（美国市场扫描）的结果进行比较。
结果
大多数无ASCVD病史的患者（>75%；48周队列）基线10年ASCVD风险较低。一名患者（托法替布5毫克BID；在所有3个队列中）发生严重感染（无菌性脑膜炎）。带状疱疹（非严重）发生在48周仅使用托法替布5毫克BID（n = 5 [1.6%]）和所有剂量托法替布（n = 7 [1.7%]；1例多皮节 [托法替布10毫克BID]）队列中。未发生死亡、机会性感染、结核病、恶性肿瘤、主要不良心血管事件、血栓栓塞事件、胃肠道穿孔。
局限性
RCT持续时间短/队列内患者数量少。
结论
托法替布5毫克BID在AS患者中48周耐受性良好；安全性与RA/PsA临床研究项目以及一组来自美国常规临床实践的AS患者一致。
临床试验注册号
NCT01786668（2013 - 02 - 06）；NCT03502616（2018 - 04 - 11）。
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