Abstract:
BACKGROUND:Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA. METHODS:This Phase 1, open-label, multiple-dose (twice daily [BID] for 5 days) study of tofacitinib in patients with active (≥ 5 joints) polyarticular course JIA was conducted from March 2013-December 2015. Patients were allocated to one of three age-based cohorts: Cohort 1, 12 to < 18 years; Cohort 2, 6 to < 12 years; and Cohort 3, 2 to < 6 years. Tofacitinib was administered according to age and body weight as tablets or oral solution (grape flavor). PK were assessed on Day 5; safety was assessed at screening, Day 1, and Day 5. Taste acceptability of the oral solution was evaluated. RESULTS:Twenty-six patients (age range 2-17 years) were enrolled: Cohort 1, N = 8; Cohort 2, N = 9; Cohort 3, N = 9; median tofacitinib doses were 5.0, 2.5, and 3.0 mg BID, respectively. The higher median tofacitinib dose in Cohort 3 versus Cohort 2 reflected implementation of an amended dosing scheme following an interim PK analysis after Cohort 2 recruitment. Geometric mean AUC at steady state (AUCtau) was 156.6 ng•h/mL in Cohort 1, 118.8 ng•h/mL in Cohort 2, and 142.5 ng•h/mL in Cohort 3; Cmax (ng/mL) was 47.0, 41.7, and 66.2, respectively. Ctrough, Cmin, and t1/2 were similar in Cohorts 2 and 3, but higher in Cohort 1. Median time to Cmax (Tmax) was similar between cohorts. Apparent clearance and volume of distribution decreased with decreasing age. Tofacitinib was well tolerated, with no serious adverse events or discontinuations due to adverse events reported. Taste acceptability was confirmed. CONCLUSIONS:PK findings from this study in children with polyarticular course JIA established dosing regimens and acceptable taste for use in subsequent studies within the tofacitinib pediatric development program. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01513902 .
journal_name
Pediatr Rheumatol Online Jjournal_title
Pediatric rheumatology online journalauthors
Ruperto N,Brunner HI,Zuber Z,Tzaribachev N,Kingsbury DJ,Foeldvari I,Horneff G,Smolewska E,Vehe RK,Hazra A,Wang R,Mebus CA,Alvey C,Lamba M,Krishnaswami S,Stock TC,Wang M,Suehiro R,Martini A,Lovell DJ,Pediatric Rheudoi
10.1186/s12969-017-0212-ysubject
Has Abstractpub_date
2017-12-28 00:00:00pages
86issue
1issn
1546-0096pii
10.1186/s12969-017-0212-yjournal_volume
15pub_type
杂志文章,多中心研究abstract:: There is a debate whether post-streptococcal reactive arthritis (PSRA) is a separate entity or a condition on the spectrum of acute rheumatic fever (ARF). We believe that PSRA is a distinct entity and in this paper we review the substantial differences between PSRA and ARF. We show how the demographic, clinical, gene...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/1546-0096-9-32
更新日期:2011-10-20 00:00:00
abstract:OBJECTIVE:To investigate concordance between physicians and parents in rating the degree of functional ability of children with juvenile idiopathic arthritis (JIA). METHODS:The attending physician and a parent were asked to rate independently the level of physical functioning of 155 patients with disease duration >/= ...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/1546-0096-5-23
更新日期:2007-12-11 00:00:00
abstract:BACKGROUND:Patient recruitment can be very challenging in paediatric studies, especially in relatively uncommon conditions, such as juvenile idiopathic arthritis (JIA). However, involving children and young people (CYP) in the design of such trials could promise a more rapid trajectory towards making evidence-based tre...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-018-0293-2
更新日期:2018-12-04 00:00:00
abstract:BACKGROUND:The aim of the study was to determine whether polymorphisms in toll-like receptor 4 (TLR4) confer susceptibility to rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population. METHODS:Genotyping for six well studied polymorphisms (rs4986790, rs4986791, rs1075...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-017-0137-5
更新日期:2017-02-21 00:00:00
abstract:BACKGROUND:Paediatric rheumatology service in Sub-Sahara African is virtually not available as there is a shortage of paediatric rheumatologists and other rheumatology health professionals. We aim to describe the clinical spectrum and the frequencies of paediatric rheumatic diseases (PRDs) in Lagos State University Tea...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-017-0139-3
更新日期:2017-01-31 00:00:00
abstract:: Recent recognition of the markedly high prevalence of temporomandibular joint (TMJ) arthritis in children with juvenile idiopathic arthritis (JIA) coupled with the significant morbidity associated with TMJ damage has prompted increased interest in both the clinical and pathological aspects of TMJ arthritis. This revi...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/1546-0096-7-11
更新日期:2009-05-29 00:00:00
abstract:BACKGROUND:To assess the predictors for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD). METHODS:A total of 560 KD patients were reviewed retrospectively, including 410 complete KD (cKD) and 150 incomplete KD (iKD) patients. The laboratory data were compared bet...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-017-0149-1
更新日期:2017-03-21 00:00:00
abstract:BACKGROUND:Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in childhood and a major cause of morbidity among children with pediatric rheumatic diseases. The management of JDM is very heterogeneous. The JDM working group of the Society for Pediatric Rheumatology (GKJR) aims to define consensus- a...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-018-0257-6
更新日期:2018-06-25 00:00:00
abstract:BACKGROUND:Deficiency of interleukin-36 receptor antagonist (DITRA) is a life threatening monogenic autoinflammatory disease caused by loss of function mutations in the IL36RN gene. Affected patients develop recurrent episodes of generalized pustular psoriasis (GPP) with systemic inflammation and fever. We here review ...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章,评审
doi:10.1186/s12969-019-0338-1
更新日期:2019-07-08 00:00:00
abstract:BACKGROUND:Kawasaki Disease (KD), the leading cause of acquired heart disease in children in the developed world, is extremely rare in neonates. We present a case of incomplete KD in a neonate and a review of the literature on neonatal KD. CASE PRESENTATION:A previously healthy full term 15 day old Caucasian male with...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章,评审
doi:10.1186/s12969-018-0263-8
更新日期:2018-07-03 00:00:00
abstract::On March 11th, 2020 the World Health Organization declared COVID-19 a global pandemic. The infection, transmitted by 2019 novel coronavirus (2019-nCov), was first discovered in December 2019, in Wuhan, Hubei Province, and then rapidly spread worldwide. Italy was early and severely involved, with a critical spread of t...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章,评审
doi:10.1186/s12969-020-00422-z
更新日期:2020-04-22 00:00:00
abstract:BACKGROUND:Juvenile Idiopathic Arthritis (JIA) may cause significant impairment in health-related quality of life (HrQoL), despite effective therapies. The aim of this study was to assess HrQoL during first-year treatment in patients with new-onset polyarticular JIA, and to compare treatment strategies. METHODS:In ACU...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12969-019-0370-1
更新日期:2019-12-16 00:00:00
abstract:BACKGROUND:Anti-TNF (Tumor necrosis factor) therapy is effective in treating pediatric patients with refractory rheumatic disease. There is however a concern that anti-TNF usage may increase the risk of malignancy. Reports on specific types of malignancy in this patient population have been emerging over the past decad...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-018-0233-1
更新日期:2018-03-14 00:00:00
abstract::In the following a brief commentary is given on a new European project that aims to provide the European countries with recommendations for the care of children and yound adults with rheumatic diseases. These recommendations will be based on surveys sent to PRINTO members and systematic literature reviews. Surveys on ...
journal_title:Pediatric rheumatology online journal
pub_type: 社论
doi:10.1186/1546-0096-11-5
更新日期:2013-02-15 00:00:00
abstract::Following publication of the original article [1], we have been notified that the colour representation of the graph is not correct in Figure 6 legend. ...
journal_title:Pediatric rheumatology online journal
pub_type: 已发布勘误
doi:10.1186/s12969-020-0405-7
更新日期:2020-02-18 00:00:00
abstract:BACKGROUND:Muckle-Wells-syndrome (MWS) is an autoinflammatory disease characterized by systemic and organ-specific inflammation due to excessive interleukin (IL)-1 release. Inner ear inflammation results in irreversible sensorineural hearing loss, if untreated. Early recognition and therapy may prevent deafness. The ai...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-015-0041-9
更新日期:2015-11-04 00:00:00
abstract:: Takayasu arteritis (TA) is a rare chronic inflammatory disease of the aorta and its major branches. It is seen predominantly in females during the second and third decades of life, although it can occur in childhood. The aetiology of TA remains unknown. To date, familial cases of TA have been considered rare; however...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/1546-0096-9-6
更新日期:2011-02-02 00:00:00
abstract:BACKGROUND:To develop and test the feasibility and initial effectiveness of the Treatment and Education Approach for Childhood-onset Lupus (TEACH) protocol, a 6-session cognitive behavioral therapy (CBT) intervention for adolescents and young adults (AYA) with childhood-onset systemic lupus erythematosus (cSLE). METHO...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-019-0307-8
更新日期:2019-02-18 00:00:00
abstract:BACKGROUND:There are few studies on radiographic outcome after long-term disease duration in juvenile idiopathic arthritis (JIA). We wanted to evaluate 29-year radiographic outcome in hands/wrists and predictors of damage in patients with long-term active JIA. METHODS:Patients diagnosed from 1980 to 1985, who had acti...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-017-0151-7
更新日期:2017-04-11 00:00:00
abstract::Mevalonate kinase deficiency (MKD), a very rare autosomal recessive autoinflammatory disease with multiple organ involvement, presents clinically as hyperimmunoglobulinemia D syndrome (HIDS), a less severe phenotype and more common form, and mevalonic aciduria (MVA), a more severe phenotype and rare form. MKD is chara...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章,评审
doi:10.1186/s12969-016-0091-7
更新日期:2016-05-04 00:00:00
abstract::Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is auto...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章,评审
doi:10.1186/s12969-016-0088-2
更新日期:2016-04-27 00:00:00
abstract:BACKGROUND:Kawasaki disease (KD) is an acute febrile systemic vasculitis that affects small and medium blood vessels. Intensified treatments for the most severely affected patients have been proposed recently, and the early identification of KD patients at high risk for coronary artery aneurysms (CAA) is crucial. Howev...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-018-0264-7
更新日期:2018-07-18 00:00:00
abstract:PURPOSE:We investigated the etiology of acute hepatitis in three children with systemic Juvenile Idiopathic Arthritis (sJIA) taking Interleukin-1 receptor antagonist (IL1RA). METHODS:Laboratory and clinical data for three children with sJIA diagnosed at ages 13 months to 8 years who developed acute hepatitis during tr...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/1546-0096-7-21
更新日期:2009-12-22 00:00:00
abstract:BACKGROUND:Recently preliminary ultrasonography (US) definitions, in B mode, for normal components of pediatric joints have been developed by the OMERACT US group. The aim of the current study was to include Doppler findings in the evaluation and definition of normal joint features that can be visualized in healthy chi...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-018-0240-2
更新日期:2018-04-10 00:00:00
abstract:BACKGROUND:Of 37 pediatric rheumatology fellowship training programs in the United States, many have three or fewer fellows at a given time, making large-scale assessment of fellow performance difficult. An objective structured clinical examination (OSCE) is a scenario-based simulation method that assesses individual p...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-019-0308-7
更新日期:2019-02-08 00:00:00
abstract:: Xanthomatous skin lesions and arthritis in children are not a common association. We present the case of a 3 year old girl who presented with xanthomatous lesions in the periungual region of both hands, around the nares and on her forehead, associated with significant arthritis that was clinically compatible with mul...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/1546-0096-7-15
更新日期:2009-10-08 00:00:00
abstract:BACKGROUND:There are controversies regarding the accuracy of the tuberculin skin test (TST) and methods based on the production of interferon gamma by sensitized T cells for the diagnosis of latent tuberculosis infection (LTBI) in pediatrics and immunosuppressed patients. Our objectives are to study TST and ELISPOT/T. ...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/1546-0096-12-17
更新日期:2014-05-22 00:00:00
abstract:BACKGROUND:To test clinical findings associated with early temporomandibular joint (TMJ) arthritis in comparison to the current gold standard contrast enhanced magnetic resonance imaging (MRI) in children with juvenile idiopathic arthritis (JIA). METHODS:Seventy-six consecutive JIA patients were included in this study...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/s12969-015-0056-2
更新日期:2015-12-09 00:00:00
abstract:BACKGROUND:Juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by persistent chronic arthritis. Disease risk is believed to be influenced by both genetic and environmental factors. It is well established that the PTPN22 single nucleotide polymorphism (SNP) rs2476601 is associated with JIA suscept...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章,多中心研究
doi:10.1186/s12969-016-0087-3
更新日期:2016-04-23 00:00:00
abstract:BACKGROUND:Due to an increased frequency of vasculitis in FMF patients, many investigators have studied MEFV mutations in patients with HSP. The aim of the study is to investigate the frequency and clinical significance of MEFV mutations in Egyptian children with Henoch-Schonlein purpura (HSP). Investigating MEFV mutat...
journal_title:Pediatric rheumatology online journal
pub_type: 杂志文章
doi:10.1186/1546-0096-12-41
更新日期:2014-09-09 00:00:00