Abstract:
BACKGROUND:Final data are presented for the ORAL Sequel long-term extension (LTE) study evaluating the safety and efficacy of tofacitinib 5 mg and 10 mg twice daily (BID) for up to 9.5 years in patients with rheumatoid arthritis (RA). METHODS:Eligible patients had previously completed a phase 1, 2, or 3 qualifying index study of tofacitinib and received open-label tofacitinib 5 mg or 10 mg BID. Stable background therapy, including csDMARDs, was continued; adjustments to tofacitinib or background therapy were permitted at investigators' discretion. Assignment to dose groups (5 mg or 10 mg BID) was based on patients' average total daily dose. The primary objective was to determine the long-term safety and tolerability of tofacitinib 5 mg and 10 mg BID; the key secondary objective was to evaluate the long-term persistence of efficacy. RESULTS:Between February 5, 2007, and November 30, 2016, 4481 patients were enrolled. Total tofacitinib exposure was 16,291 patient-years. Safety data are reported up to month 114 for all tofacitinib; efficacy data are reported up to month 96 for tofacitinib 5 mg BID and month 72 for 10 mg BID (with low patient numbers limiting interpretation beyond these time points). Overall, 52% of patients discontinued (24% due to adverse events [AEs] and 4% due to insufficient clinical response); the safety profile remained consistent with that observed in prior phase 1, 2, 3, or LTE studies. The incidence rate (IR; number of patients with events per 100 patient-years) for AEs leading to discontinuation was 6.8. For all-cause AEs of special interest, IRs were 3.4 for herpes zoster, 2.4 for serious infections, 0.8 for malignancies excluding non-melanoma skin cancer, 0.4 for major adverse cardiovascular events, and 0.3 for all-cause mortality. Clinically meaningful improvements in the signs and symptoms of RA and physical functioning, which were observed in the index studies, were maintained. CONCLUSIONS:Tofacitinib 5 mg and 10 mg BID demonstrated a consistent safety profile (as monotherapy or combination therapy) and sustained efficacy in this open-label LTE study of patients with RA. Safety data are reported up to 9.5 years, and efficacy data up to 8 years, based on adequate patient numbers to support conclusions. TRIAL REGISTRATION:NCT00413699 , funded by Pfizer Inc (date of trial registration: December 20, 2006).
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Wollenhaupt J,Lee EB,Curtis JR,Silverfield J,Terry K,Soma K,Mojcik C,DeMasi R,Strengholt S,Kwok K,Lazariciu I,Wang L,Cohen Sdoi
10.1186/s13075-019-1866-2subject
Has Abstractpub_date
2019-04-05 00:00:00pages
89issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-019-1866-2journal_volume
21pub_type
临床试验,杂志文章,多中心研究abstract:INTRODUCTION:Pathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which, in addition to bone erosion, demonstrates bone formation at the time of clinical manifestations. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0531-7
更新日期:2015-03-05 00:00:00
abstract::Mammalian immune responses are intended to eradicate microbial pathogens and thus protect individuals from the harmful effects of such infections. However, unresolved inflammation can be devastating to the host and cause tissue damage and organ malfunction. Immune responses can even mistakenly target self-antigens and...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4131
更新日期:2013-01-25 00:00:00
abstract:INTRODUCTION:The interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis. METHODS:Human CD14+ cells were isolated fro...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2936
更新日期:2010-01-01 00:00:00
abstract::Mycophenolate mofetil (MMF) is an immunosuppressant drug being used for induction and maintenance of remission of lupus nephritis in systemic lupus erythematosus. Evidence about its use was sought from full publications and abstracts of randomised trials and cohort studies by using a variety of search strategies. Effi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/ar2093
更新日期:2006-01-01 00:00:00
abstract::Glucocorticoids have successfully been used in the treatment of rheumatoid arthritis. Data suggest that 7alpha-hydroxy-dehydroepiandrosterone (7alpha-OH-DHEA), an immunostimulating metabolite of dehydroepiandrosterone, can block glucocorticoid-induced immune suppression. Formation of 7alpha-OH-DHEA is catalyzed by act...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1819
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Proprotein convertase subtilisin kexin 9 (PCSK9) targets the LDL-receptor (LDLR) which raises LDL-levels. In addition, PCSK9 has proinflammatory immunological effects. Here, we investigate the role of PCSK9 in relation to the inflammatory activity in patients with rheumatoid arthritis (RA). METHODS:PCSK9-le...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02386-7
更新日期:2021-01-19 00:00:00
abstract::Although it is generally accepted that osteoarthritis is a degenerative condition of the cartilage, other tissues such as synovium in which immunological and inflammatory reactions occur contribute to the development of joint pathology. This sheds new light on the potential mechanism of action of mesenchymal stem cell...
journal_title:Arthritis research & therapy
pub_type: 社论
doi:10.1186/ar4190
更新日期:2013-03-20 00:00:00
abstract:BACKGROUND:RA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA....
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0982-5
更新日期:2016-04-12 00:00:00
abstract:BACKGROUND:Osteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (H2S) has been implicated in mineralization but has never been studied in OA. Here, we investigated t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02147-6
更新日期:2020-03-17 00:00:00
abstract:INTRODUCTION:Our objectives were to examine mononuclear cell gene expression profiles in patients with systemic lupus erythematosus (SLE) and healthy controls and to compare subsets with and without atherosclerosis to determine which genes' expression is related to atherosclerosis in SLE. METHODS:Monocytes were obtain...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4609
更新日期:2014-07-10 00:00:00
abstract:INTRODUCTION:Varied definitions of disc pathology exist in the literature. Magnetic Resonance Imaging (MRI) classification systems incorporate several qualitative features including disc appearance, the distinction between the nucleus and the annulus, signal intensity and intervertebral disc height. The lack of a conti...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0820-1
更新日期:2015-10-23 00:00:00
abstract:INTRODUCTION:Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of a...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0814-z
更新日期:2015-10-22 00:00:00
abstract::Antineutrophil antibodies are well recognized causes of neutropenia, producing both quantitative and qualitative defects in neutrophils and increased risk for infection. In primary autoimmune neutropenia (AIN) of infancy, a moderate to severe neutropenia is the sole abnormality; it is rarely associated with serious in...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1803
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:The objective of this study was to assess natural microbial agents, history and risk factors for total joint arthroplasty (TJA) infections in patients receiving tumor necrosis factor (TNF)α-blockers, through the French RATIO registry and a case-control study. METHODS:Cases were TJA infections during TNFα-...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3087
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:The purpose of this study was to evaluate the effects of L-4F, an apolipoprotein A-1 mimetic peptide, alone or with pravastatin, in apoE-/-Fas-/-C57BL/6 mice that spontaneously develop immunoglobulin G (IgG) autoantibodies, glomerulonephritis, osteopenia, and atherosclerotic lesions on a normal chow diet. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3020
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Angiogenesis plays a critical role in synovial inflammation and joint destruction in rheumatoid arthritis (RA). Vascular endothelial growth factor A (VEGF-A) and angiopoietins are two important mediators of synovial angiogenesis. We have previously developed a novel chimeric decoy receptor, namely, double-...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4265
更新日期:2013-08-14 00:00:00
abstract:BACKGROUND:To determine whether lung involvement is related to microvascular perturbations, nailfold videocapillaroscopy (NVC) was performed in patients with systemic sclerosis (SSc). METHODS:A cross-sectional study was consecutively accomplished in 152 SSc patients. NVC, a pulmonary function test and echocardiography...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1775-9
更新日期:2018-12-19 00:00:00
abstract:INTRODUCTION:Serious infection, cardiovascular disease, and mortality are increased in rheumatoid arthritis (RA). Whether RA affects the risk for these complications after total joint arthroplasty (TJA) is unknown, we hypothesize that it does. We compared the occurrence of 30-day postoperative complications and mortali...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4385
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:Immunological studies of giant cell arteritis (GCA) suggest that a triggering antigen of unknown nature could generate a specific immune response. We thus decided to detect autoantibodies directed against endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in the serum of GCA patients and to i...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3388
更新日期:2011-06-28 00:00:00
abstract:INTRODUCTION:The objective was to study the potential genetic contribution of Toll-like receptor (TLR) genes in rheumatoid arthritis (RA). TLRs bind to pathogen-associated molecular patterns, and TLR genes influence both proinflammatory cytokine production and autoimmune responses. Host-pathogen interactions are involv...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2589
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:A number of occupational risk factors are discussed in relation to the development and progress of knee joint diseases (for example, working in a kneeling or squatting posture, lifting and carrying heavy weights). Besides the occupational factors, a number of individual risk factors are important. The dist...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3015
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Physical activity has been recommended to patients with knee osteoarthritis for improving their symptoms. However, it is still controversial if physical activity has effects on joint structures including cartilage volume. The aim of this study was to describe the associations between physical activity and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0813-0
更新日期:2015-10-26 00:00:00
abstract::This review summarizes the immunological consequences of biological therapies used in juvenile idiopathic arthritis (JIA). For every frequently used biological agent the characteristics are clearly specified (molecular target, isotype, registered indication for JIA, route of administration, half-life, contraindication...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4213
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:The patients with RA benefit from early identification soon after the first clinical symptoms appear. The 2010 ACR/EULAR classification criteria were developed to fulfill this need and their application has been demonstrated to be effective. However, there is still room for improvement. Therefore, we aimed t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2079-4
更新日期:2019-12-11 00:00:00
abstract:BACKGROUND:Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term stru...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2043-3
更新日期:2019-12-04 00:00:00
abstract::Over the last decades, genetic factors for rheumatoid diseases like the HLA haplotypes have been studied extensively. However, during the past years of research, it has become more and more evident that the influence of epigenetic processes on the development of rheumatic diseases is probably as strong as the genetic ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2500
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Risk prediction algorithms increase understanding of which patients are at greatest risk of a harmful outcome. Our goal was to create a clinically useful prediction algorithm for structural progression of knee osteoarthritis (OA), using medial joint space loss as a proxy; and to quantify the benefit of inclu...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-017-1291-3
更新日期:2017-05-16 00:00:00
abstract:INTRODUCTION:The efficacy and the optimal type and volume of aerobic exercise (AE) in fibromyalgia syndrome (FMS) are not established. We therefore assessed the efficacy of different types and volumes of AE in FMS. METHODS:The Cochrane Library, EMBASE, MEDLINE, PsychInfo and SPORTDISCUS (through April 2009) and the re...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/ar3002
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Our objective was to examine the role of the janus-activated kinase (JAK) pathway in the modulation of tumor necrosis factor-α (TNF)-induced-IL-18 bioactivity by reduction of caspase-1 function. METHODS:Caspase-1 expression in rheumatoid arthritis (RA) synovial fibroblasts treated with TNF was assessed by...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4551
更新日期:2014-04-24 00:00:00
abstract:INTRODUCTION:Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultra...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3742
更新日期:2012-02-15 00:00:00