Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor

详细信息    查看全文

• 作者：Christina Charles-Schoeman ; MD^a ; ^{ccharles@mednet.ucla.edu} ; Pierre Wicker ; MD^b ; Miguel A. Gonzalez-Gay ; MD ; PhD^c ; Mary Boy ; MD^d ; Andrea Zuckerman ; MD^e ; Koshika Soma ; MD^d ; Jamie Geier ; PhD^f ; Kenneth Kwok ; MSc^f ; Richard Riese ; MD ; PhD^d
• 关键词：AE ; adverse event ; ACR ; American College of Rheumatology ; Apo ; apolipoprotein ; BID ; twice daily ; BP ; blood pressure ; CHF ; congestive heart failure ; CRP ; C-reactive protein ; csDMARD ; conventional synthetic disease-modifying antirheumatic drug ; CV ; cardiovascular ; DBP ; diastolic blood pressure ; DMARD ; disease-modifying antirheumatic drug ; ESR ; erythrocyte sedimentation rate ; HDL-C ; high-density lipoprotein cholesterol ; IR ; inadequate response ; LDL-C ; low-density lipoprotein cholesterol ; LTE ; long-
• 刊名：Seminars in Arthritis and Rheumatism
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：46
• 期：3
• 页码：261-271
• 全文大小：1356 K
• 卷排序：46

文摘

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The implications of treatment with tofacitinib on cardiovascular (CV) risk in RA are unknown. Therefore, CV adverse events (AEs), and blood pressure and lipid level changes, in tofacitinib-treated patients with RA were evaluated.MethodsData were pooled from six Phase (P)3 studies (24 months) and two open-label long-term extension (LTE) studies (60 months) of tofacitinib in patients with RA and inadequate response to DMARDs. Tofacitinib was administered alone or with non-biologic DMARDs. CV events, including major adverse CV events (MACE: CV death and non-fatal CV events) and congestive heart failure (CHF), were assessed by a blinded adjudication committee.ResultsOverall, 4271 patients from P3 studies and 4827 enrolled from P2/P3 studies into LTE studies were evaluated, representing 3942 and 8699 patient-years of exposure to tofacitinib, respectively. Blood pressure remained stable over time across studies. The number of investigator-reported hypertension-related AEs in tofacitinib-treated patients was low in P3 studies (Months 0–3: 2.8%; Months 3–6: 1.4%; >6 months: 2.8%). Across studies, lipid level increases were generally observed within 1–3 months of treatment and stabilized thereafter. Patients with events (incidence rate [IR]/100 patient-years) for MACE and CHF, respectively, were: 23 (0.58) and 9 (0.23) in P3 studies, and 32 (0.37) and 8 (0.09) in LTE studies; IRs were comparable with placebo (P3) and did not increase over time (LTE).ConclusionsTofacitinib was associated with a low incidence of CV events in a large Phase 3 program, including LTE studies. Further long-term studies are underway.