Integrated safety analysis of tofacitinib from Phase 2 and 3 trials of patients with ankylosing spondylitis.

IF 2 4区医学 Q3 RHEUMATOLOGY

Advances in Rheumatology Pub Date : 2024-12-18 DOI:10.1186/s42358-024-00402-x

Atul Deodhar, Servet Akar, Jeffrey R Curtis, Bassel El-Zorkany, Marina Magrey, Cunshan Wang, Joseph Wu, Solomon B Makgoeng, Ivana Vranic, Sujatha Menon, Dona L Fleishaker, Annette M Diehl, Lara Fallon, Arne Yndestad, Robert B M Landewé

{"title":"Integrated safety analysis of tofacitinib from Phase 2 and 3 trials of patients with ankylosing spondylitis.","authors":"Atul Deodhar, Servet Akar, Jeffrey R Curtis, Bassel El-Zorkany, Marina Magrey, Cunshan Wang, Joseph Wu, Solomon B Makgoeng, Ivana Vranic, Sujatha Menon, Dona L Fleishaker, Annette M Diehl, Lara Fallon, Arne Yndestad, Robert B M Landewé","doi":"10.1186/s42358-024-00402-x","DOIUrl":null,"url":null,"abstract":"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).","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"64 1","pages":"87"},"PeriodicalIF":2.0000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s42358-024-00402-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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).

查看原文本刊更多论文

强直性脊柱炎患者2期和3期临床试验中托法替尼的综合安全性分析。

目的：通过对强直性脊柱炎（AS）患者的随机对照试验（rct）的综合分析，描述托法替尼的安全性。方法：将2期(NCT01786668；2013年4月- 2015年3月)/第3期(NCT03502616；分析AS患者的随机对照试验（3个重叠队列）：16周安慰剂对照(托法替尼5 mg，每日2次[BID] [n = 185]；安慰剂[n = 187])；48周仅托法替尼5mg BID (n = 316)；48周全托法替尼(≥1剂量托法替尼2,5或10mg BID；n = 420)。在没有ASCVD病史的患者（48周队列）中确定基线10年动脉粥样硬化性心血管疾病（ASCVD）风险。对不良事件(ae)/特殊关注的ae进行评估/与其他托法替尼项目的结果进行比较(16例2期/ 3期类风湿关节炎[RA]；2项3期银屑病关节炎（PsA）随机对照试验（rct）和一项现实世界AS患者启动生物疾病改善抗风湿药物的队列研究（US MarketScan）。结果：大多数患者(bb0 75%；没有ASCVD病史的48周队列的基线10年ASCVD风险较低。1例患者(托法替尼5mg BID；所有3组患者均有严重感染（无菌性脑膜炎）。带状疱疹（非严重）发生在48周仅托法替尼5mg BID组（n = 5[1.6%]）和全托法替尼组（n = 7 [1.7%]）；一个多皮瘤[托法替尼10 mg BID])队列。无死亡、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、胃肠道穿孔发生。局限性：RCT持续时间短/队列内患者人数少。结论：托法替尼5mg BID对AS患者48周耐受性良好；安全性与RA/PsA临床项目和来自美国常规临床实践的AS患者队列一致。临床试验注册号：NCT01786668 (2013-02-06)；NCT03502616(2018-04-11)。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Advances in Rheumatology Medicine-Rheumatology

CiteScore

4.00

自引率

4.30%

发文量

审稿时长

53 weeks

期刊介绍： Formerly named Revista Brasileira de Reumatologia, the journal is celebrating its 60th year of publication. Advances in Rheumatology is an international, open access journal publishing pre-clinical, translational and clinical studies on all aspects of paediatric and adult rheumatic diseases, including degenerative, inflammatory and autoimmune conditions. The journal is the official publication of the Brazilian Society of Rheumatology and welcomes original research (including systematic reviews and meta-analyses), literature reviews, guidelines and letters arising from published material.