Efficacy and safety of tofacitinib in Chinese patients with active psoriatic arthritis: a phase 3, randomised, double-blind, placebo-controlled study

被引:21
作者
Leng, Xiaomei [1 ]
Lin, Wei [2 ]
Liu, Shixue [3 ]
Kanik, Keith [4 ]
Wang, Cunshan [4 ]
Wan, Weiguo [5 ]
Jiang, Zhenyu [6 ]
Liu, Yi [7 ]
Liu, Shengyun [8 ]
Zhang, Zhuoli [9 ]
Zhang, Zhiyi [10 ]
Xu, Jian [11 ]
Tan, Wenfeng [12 ]
Hu, Jiankang [13 ]
Li, Jingyang [14 ]
Liu, Ju [15 ]
Gunay, Levent M. [16 ]
Dina, Oluwaseyi [17 ]
Kinch, Cassandra [18 ]
Zeng, Xiaofeng [1 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Natl Clin Res Ctr Dermatol & Immunol Dis, Dept Rheumatol & Clin Immunol,Key Lab Rheumatol &, Beijing, Peoples R China
[2] Pfizer Inc, Beijing, Peoples R China
[3] Pfizer Inc, Shanghai, Peoples R China
[4] Pfizer Inc, Groton, CT USA
[5] Fudan Univ, Huashan Hosp, Shanghai, Peoples R China
[6] First Affiliated Hosp Jilin Univ, Changchun, Peoples R China
[7] Sichuan Huaxi Hosp, Chengdu, Sichuan, Peoples R China
[8] Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Peoples R China
[9] Peking Univ First Hosp, Beijing, Peoples R China
[10] Harbin Med Univ, Affiliated Hosp 1, Harbin, Peoples R China
[11] Kunming Med Univ, Affiliated Hosp 1, Kunming, Peoples R China
[12] Jiangsu Prov Hosp, Nanjing, Peoples R China
[13] Pingxiang Peoples Hosp, Pingxiang, Peoples R China
[14] Zhuzhou Cent Hosp, Zhuzhou, Peoples R China
[15] Jiujiang No 1 Peoples Hosp, Jiujiang, Peoples R China
[16] Pfizer Inc, Istanbul, Turkiye
[17] Pfizer Inc, New York, NY USA
[18] Pfizer Canada ULC, Kirkland, PQ, Canada
关键词
Arthritis; Psoriatic; Inflammation; RHEUMATOID-ARTHRITIS; INADEQUATE RESPONSE; OPEN-LABEL; METHOTREXATE; RECOMMENDATIONS; ADALIMUMAB; COMBINATION; MONOTHERAPY; CP-690,550; MANAGEMENT;
D O I
10.1136/rmdopen-2022-002559
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to >= 1 conventional synthetic disease-modifying antirheumatic drug.Methods Patients were randomised (2:1) to tofacitinib 5 mg twice daily (N=136) or placebo (N=68); switched to tofacitinib 5 mg twice daily after month (M)3 (blinded). Primary endpoint: American College of Rheumatology (ACR50) response at M3. Secondary endpoints (through M6) included: ACR20/50/70 response; change from baseline in Health Assessment Questionnaire-Disability Index (HAQ- DI); >= 75% improvement in Psoriasis Area and Severity Index (PASI75) response, and enthesitis and dactylitis resolution. Safety was assessed throughout.Results The primary endpoint was met (tofacitinib 5 mg twice daily, 38.2%; placebo, 5.9%; p < 0.0001). M3 ACR20/ACR70/PASI75 responses, and enthesitis and dactylitis resolution rates, were higher and HAQ- DI reduction was greater for tofacitinib 5 mg twice daily versus placebo. Incidence of adverse events (AEs)/ serious AEs (M0-3): 68.4%/0%, tofacitinib 5 mg twice daily; 75.0%/4.4%, placebo. One death was reported with placebo -> tofacitinib 5 mg twice daily (due to accident). One serious infection, non-serious herpes zoster, and lung cancer case each were reported with tofacitinib 5 mg twice daily; four serious infections and one non-serious herpes zoster case were reported with placebo -> tofacitinib 5 mg twice daily (M0-6). No non-melanoma skin cancer, major adverse cardiovascular or thromboembolism events were reported. Conclusion In Chinese patients with PsA, tofacitinib efficacy was greater than placebo (primary and secondary endpoints). Tofacitinib was well tolerated; safety outcomes were consistent with the established safety profile in PsA and other indications.
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相关论文
共 37 条
[1]   Adverse events of special interest in clinical trials of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and psoriasis with 37 066 patient-years of tofacitinib exposure [J].
Burmester, Gerd R. ;
Nash, Peter ;
Sands, Bruce E. ;
Papp, Kim ;
Stockert, Lori ;
Jones, Thomas, V ;
Tan, Huaming ;
Madsen, Ann ;
Valdez, Hernan ;
Cohen, Stanley B. .
RMD OPEN, 2021, 7 (02)
[2]   Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial [J].
Burmester, Gerd R. ;
Blanco, Ricardo ;
Charles-Schoeman, Christina ;
Wollenhaupt, Juergen ;
Zerbini, Cristiano ;
Benda, Birgitta ;
Gruben, David ;
Wallenstein, Gene ;
Krishnaswami, Sriram ;
Zwillich, Samuel H. ;
Koncz, Tamas ;
Soma, Koshika ;
Bradley, John ;
Mebus, Charles .
LANCET, 2013, 381 (9865) :451-460
[3]   Rheumatoid arthritis management in the APLAR region: Perspectives from an expert panel of rheumatologists, patients and community oriented program for control of rheumatic diseases [J].
Chopra, Arvind ;
Lin, Hsiao-Yi ;
Navarra, Sandra, V ;
Saeed, Muhammad Ahmed ;
Sockalingam, Sargunan ;
Thongpooswan, Supat ;
Jois, Ramesh ;
Salim, Babur ;
Lee, Ka Wing Gavin ;
Lau, Tang Ching ;
Wee, James .
INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, 2021, 24 (09) :1106-1111
[4]   THE GROUP FOR RESEARCH AND ASSESSMENT OF PSORIASIS AND PSORIATIC ARTHRITIS (GRAPPA) TREATMENT RECOMMENDATIONS 2021 [J].
Coates, L. C. ;
Soriano, E. ;
Corp, N. ;
Bertheussen, H. ;
Callis-Duffin, K. ;
Campanholo, C. Barbosa ;
Chau, J. ;
Eder, L. ;
Fernandez, D. ;
Fitzgerald, O. ;
Garg, A. ;
Gladman, D. D. ;
Goel, N. ;
Grieb, S. ;
Helliwell, P. ;
Husni, M. E. ;
Jadon, D. ;
Katz, A. ;
Laheru, D. ;
Latella, J. ;
Leung, Y. Y. ;
Lindsay, C. ;
Lubrano, E. ;
Mazzuoccolo, L. ;
Mcdonald, R. ;
Mease, P. J. ;
O'sullivan, D. ;
Ogdie, A. ;
Olsder, W. ;
Schick, L. ;
Steinkoenig, I. ;
De Wit, M. ;
Van der Windt, D. ;
Kavanaugh, A. .
ANNALS OF THE RHEUMATIC DISEASES, 2021, 80 :139-140
[5]   Psoriatic arthritis: state of the art review [J].
Coates, Laura C. ;
Helliwell, Philip S. .
CLINICAL MEDICINE, 2017, 17 (01) :65-70
[6]  
Eder L, 2020, ARTHRITIS RHEUMATOL, V72
[7]   Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial [J].
Fleischmann, Roy ;
Mysler, Eduardo ;
Hall, Stephen ;
Kivitz, Alan J. ;
Moots, Robert J. ;
Luo, Zhen ;
DeMasi, Ryan ;
Soma, Koshika ;
Zhang, Richard ;
Takiya, Liza ;
Tatulych, Svitlana ;
Mojcik, Christopher ;
Krishnaswami, Sriram ;
Menon, Sujatha ;
Smolen, Josef S. .
LANCET, 2017, 390 (10093) :457-468
[8]   Placebo-Controlled Trial of Tofacitinib Monotherapy in Rheumatoid Arthritis [J].
Fleischmann, Roy ;
Kremer, Joel ;
Cush, John ;
Schulze-Koops, Hendrik ;
Connell, Carol A. ;
Bradley, John D. ;
Gruben, David ;
Wallenstein, Gene V. ;
Zwillich, Samuel H. ;
Kanik, Keith S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (06) :495-507
[9]   Impact of baseline body mass index on the efficacy and safety of tofacitinib in patients with psoriatic arthritis [J].
Giles, Jon T. ;
Ogdie, Alexis ;
Gomez Reino, Juan J. ;
Helliwell, Philip ;
Germino, Rebecca ;
Stockert, Lori ;
Young, Pamela ;
Joseph, Wael ;
Mundayat, Rajiv ;
Graham, Daniela ;
Ritchlin, Christopher .
RMD OPEN, 2021, 7 (01)
[10]   Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors [J].
Gladman, Dafna ;
Rigby, William ;
Azevedo, Valderilio F. ;
Behrens, Frank ;
Blanco, Ricardo ;
Kaszuba, Andrzej ;
Kudlacz, Elizabeth ;
Wang, Cunshan ;
Menon, Sujatha ;
Hendrikx, Thijs ;
Kanik, Keith S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (16) :1525-1536