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1.
Arthritis Rheumatol ; 71(3): 451-459, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30225949

RESUMO

OBJECTIVE: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). METHODS: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman's rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal. RESULTS: Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = -0.36). CONCLUSION: Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/sangue , Artrite Juvenil/tratamento farmacológico , Calgranulina A/sangue , Calgranulina B/sangue , Proteína S100A12/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Quimioterapia de Manutenção/métodos , Masculino , Exacerbação dos Sintomas , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Suspensão de Tratamento
2.
Arthritis Rheumatol ; 70(9): 1508-1518, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29604189

RESUMO

OBJECTIVE: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease. METHODS: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. RESULTS: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05). CONCLUSION: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/patologia , Quimioterapia de Indução/estatística & dados numéricos , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Lactente , Tábuas de Vida , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Exacerbação dos Sintomas , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
3.
Arthritis Rheumatol ; 70(4): 594-605, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29287303

RESUMO

OBJECTIVE: The nuclear oncoprotein DEK is an autoantigen associated with juvenile idiopathic arthritis (JIA), especially the oligoarticular subtype. DEK is a secreted chemotactic factor. Abundant levels of DEK and DEK autoantibodies are found in inflamed synovium in JIA. We undertook this study to further characterize the nature of DEK autoantibodies in screening serum samples from 2 different cohorts that consisted mostly of patients with JIA. METHODS: DEK autoantibody levels were analyzed in sera from 33 JIA patients, 13 patients with other inflammatory conditions, and 11 healthy controls, as well as in 89 serum samples from JIA patients receiving anti-tumor necrosis factor (anti-TNF) therapy. Recombinant His-tagged full-length DEK protein (1-375 amino acids [aa]) and the 187-375-aa and 1-350-aa His-tagged DEK fragments made in a baculovirus system were used for enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The C-terminal 25-aa fragment of DEK was expressed in a glutathione S-transferase-tagged vector. ELISA results were calculated as area under the curve by the trapezoidal rule. RESULTS: DEK autoantibody levels were significantly higher in patients with polyarticular JIA than in those with oligoarticular JIA, and were higher in patients with polyarticular JIA who had more active disease after cessation of anti-TNF therapy. Immunoblotting against the C-terminal 25-aa fragment of DEK confirmed that this section of the DEK molecule is the most immunogenic domain. CONCLUSION: DEK autoantibody levels are higher in patients with polyarticular JIA than in those with oligoarticular JIA, and higher in patients who have disease flares after cessation of anti-TNF therapy. The C-terminal 25-aa fragment is the most immunogenic portion of DEK. These findings are significant with respect to the nature of DEK autoantibodies, their contribution to JIA pathogenesis, and their implications for JIA management.


Assuntos
Antirreumáticos/imunologia , Artrite Juvenil/sangue , Autoanticorpos/sangue , Proteínas Cromossômicas não Histona/imunologia , Proteínas Oncogênicas/imunologia , Proteínas de Ligação a Poli-ADP-Ribose/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/imunologia , Autoanticorpos/imunologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Exacerbação dos Sintomas , Suspensão de Tratamento
4.
Arthritis Care Res (Hoboken) ; 67(4): 529-37, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25331530

RESUMO

OBJECTIVE: Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product-based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4-year (2008-2012) EDSSP. METHODS: Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6-month period. Reporting rates were calculated per 100 person-years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution. RESULTS: Thirty-seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person-years (95% CI 0.95-1.19). The rates for SAEs and IMEs were 0.54 per 100 person-years (95% CI 0.45-0.63) and 0.53 per 100 person-years (95% CI 0.49-0.62), respectively. CONCLUSION: The EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product-based registry.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Antirreumáticos/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Médicos , Vigilância da População/métodos , Reumatologia/métodos , Adolescente , Sistemas de Notificação de Reações Adversas a Medicamentos/tendências , Artrite Juvenil/diagnóstico , Artrite Juvenil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Médicos/tendências , Projetos de Pesquisa/tendências , Reumatologia/tendências
5.
Artigo em Inglês | MEDLINE | ID: mdl-25057265

RESUMO

BACKGROUND: This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs). METHODS: Children aged ≥2 to <18 years with rheumatoid-factor-positive or -negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database. RESULTS: A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use. CONCLUSIONS: The safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00688545.


Assuntos
Anti-Inflamatórios não Esteroides , Artrite Juvenil/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pirazóis/efeitos adversos , Sulfonamidas/efeitos adversos , Adolescente , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/classificação , Celecoxib , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Masculino , Conduta do Tratamento Medicamentoso , Segurança do Paciente , Pirazóis/administração & dosagem , Sistema de Registros , Sulfonamidas/administração & dosagem , Tempo , Estados Unidos
6.
Arthritis Care Res (Hoboken) ; 64(4): 546-53, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22076847

RESUMO

OBJECTIVE: To use consensus methods and the considerable expertise contained within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) organization to extend the 3 previously developed treatment plans for moderate juvenile dermatomyositis (DM) to span the full course of treatment. METHODS: A consensus meeting was held in Chicago on April 23-24, 2010, involving 30 pediatric rheumatologists and 4 lay participants. Nominal group technique was used to achieve consensus on treatment plans that represented typical management of moderate juvenile DM. A preconference survey of CARRA, completed by 151 (56%) of 272 members, was used to provide additional guidance to the discussion. RESULTS: Consensus was reached on timing and rate of steroid tapering, duration of steroid therapy, and actions to be taken if patients were unchanged, worsening, or experiencing medication side effects or disease complications. Of particular importance, a single consensus steroid taper was developed. CONCLUSION: We were able to develop consensus treatment plans that describe therapy for moderate juvenile DM throughout the treatment course. These treatment plans can now be used clinically, and data collected prospectively regarding treatment effectiveness and toxicity. This will allow comparison of these treatment plans and facilitate the development of evidence-based treatment recommendations for moderate juvenile DM.


Assuntos
Dermatomiosite/tratamento farmacológico , Guias de Prática Clínica como Assunto , Esteroides/uso terapêutico , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Medicina Baseada em Evidências , Humanos , Fatores de Tempo , Resultado do Tratamento
7.
Arthritis Rheum ; 57(6): 1000-6, 2007 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-17665465

RESUMO

OBJECTIVE: To assess the reliability and concurrent validity of the Medication Adherence Self-report Inventory (MASRI) when used in systemic lupus erythematosus (SLE), to investigate the predictive validity of the MASRI using pharmacy refill information as the criterion standard, and to propose a sensible approach to the screening for nonadherence in a clinical setting. METHODS: Adherence to 2 medications (hydroxychloroquine and prednisone) was measured in 55 patients using the MASRI, pill counts, and physician ratings (MD scale). Adherence based on pharmacy refill information served as a criterion standard with nonadherence defined as adherence rates <80%. To determine test-rest reliability of the MASRI, 20 patients completed the measure twice within a 2-week period. RESULTS: Using pharmacy information, 39% of the patients were nonadherent to prednisone and 51% to hydroxychloroquine. The MASRI had acceptable internal consistency (Cronbach's alpha 0.7) and good reliability. Irrespective of the drug assessed, MASRI ratings were moderately correlated with patient adherence (pharmacy), supporting the concurrent validity of the MASRI. The combination of adherence estimation by MD scale rating at <85% and by MASRI at <90% was 87% sensitive and 86% specific for identifying patients who were nonadherent to prednisone. These cutoff values also appeared suitable for identifying nonadherence to hydroxychloroquine. CONCLUSION: The MASRI is a reliable measure of adherence to medications in SLE. The measure has concurrent and predictive validity. When combined with the MD scale, the MASRI appears to be a useful screening tool for nonadherence in patients with SLE that could be suitable for clinical practice.


Assuntos
Antirreumáticos/uso terapêutico , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Prednisona/uso terapêutico , Inquéritos e Questionários , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Farmácias/estatística & dados numéricos , Projetos Piloto , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
8.
Rheum Dis Clin North Am ; 31(3): 483-96, vii, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16084320

RESUMO

This article discusses the literature on pediatric-onset mixed connective tissue disease (MCTD) and adds 34 new cases. Although not benign, pediatric-onset MCTD carries less mortality than adult-onset disease.


Assuntos
Doença Mista do Tecido Conjuntivo , Idade de Início , Anticorpos/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença Mista do Tecido Conjuntivo/epidemiologia , Doença Mista do Tecido Conjuntivo/etiologia , Prognóstico , Ribonucleoproteínas/imunologia
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