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OBJECTIVE: To report pharmacokinetics (PK), immunogenicity, clinical effect, and safety of intravenous (IV) golimumab in children with active polyarticular-course juvenile idiopathic arthritis (pcJIA) who participated in A Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Intravenous Golimumab in Pediatric Participants With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy (GO-VIVA)'s open-label, long-term extension (LTE) through week 252. METHODS: GO-VIVA participants who continued IV golimumab (80 mg/m2 every 8 weeks) after week 52 were included. PK and safety were assessed through week 244 (last dose) and week 252, respectively, and clinical response through week 116. Clinical outcomes included JIA-American College of Rheumatology (ACR) responses and clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10). Binary outcomes used nonresponder imputation, and other descriptive analyses used observed data. RESULTS: Of 112/127 (88.2%) participants entering the LTE, 69 completed the week 252 visit. Median steady-state trough golimumab concentrations were generally maintained from week 52 through week 244 (range 0.3-0.6 µg/mL). Antigolimumab antibody rates were consistent through week 52 (39.2% [49/125]) and week 244 (44.8% [56/125]). Week 52 JIA-ACR 30/50/70/90 response rates (75.6% [96/127], 74% [94/127], 65.4% [83/127], and 48.8% [62/127], respectively) were generally maintained through week 116 (72.4% [92/127], 71.7% [91/127], 63.8% [81/127], and 50.4% [64/127], respectively), when the median cJADAS10 was 1.6 and 56.7% (72/127) of participants achieved cJADAS10 ≤ 5 (minimal disease activity). Rates (per 100 patient-years) of serious adverse events and serious infections through week 252 were 7.7 and 3.9, respectively. CONCLUSION: GO-VIVA LTE participants experienced adequate PK exposure and stable safety and immunogenicity. The majority of participants experienced no more than minimal residual disease activity. Data suggest IV golimumab treatment provided durable clinical response through week 116, with an acceptable risk-benefit profile.
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OBJECTIVES: To assess the heterogeneity in factors affecting physician's global assessment of disease activity (PhGA) and in PhGA scoring of multiple JIA patient's case scenarios. METHODS: An electronic web-based questionnaire of factors potentially considered in PhGA was sent worldwide to members of PRINTO and the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN). The respondents were asked to rate from 0 to 100 the relevance of 17 factors possibly affecting PhGA scoring and to derive a PhGA score of 17 detailed JIA patient cases. The median and interquartile range was used to measure the heterogeneity in the scoring. To demonstrate the consistency among the PhGA scores of the patient cases provided by multiple physicians, we assessed the inter-rater reliability using intra-class correlation. RESULTS: The questionnaire was completed by 491 respondents. A large individual variation was observed in the impact of different factors on PhGA when assessing JIA. For non-systemic JIA the presence of fever had the largest variation and swollen joint count had the smallest. For sJIA, the largest variation was seen in the presence of erosions and the smallest in the presence of fever. The intra-class correlation of the group for PhGA scoring of patient cases was 0.53 (95% CI 0.38, 0.72). CONCLUSIONS: In a sample of worldwide respondents, the scoring of the PhGA is divergent. Consensus on PhGA scoring guidelines is required to obtain a consistent assessment of patients.
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Artritis Juvenil , Médicos , Niño , Humanos , Artritis Juvenil/diagnóstico , Reproducibilidad de los Resultados , Reumatólogos , Encuestas y CuestionariosRESUMEN
AIM: To assess safety of COVID-19 vaccination in paediatric patients with immune-mediated inflammatory disease (IMID). METHODS: Subjects of 5-21 years of age with IMID who received at least one COVID-19 vaccine completed electronic surveys after each vaccine to assess side effects within 1 week of vaccination, current medications and COVID-19 testing after vaccination. Charts were reviewed for COVID-19 polymerase chain reaction and IgG response to SARS-CoV-2 spike protein results and for disease flare during the study period. RESULTS: Among 190 enrolled subjects, 71% were female, with median age 17 (range 6-21) years. The most common diagnosis was juvenile idiopathic arthritis/rheumatoid arthritis (55%). 78% of subjects were taking immunosuppressive medication. At least one side effect was reported in 65% of subjects after any dose of the vaccine; with side effects in 38%, 53% and 55% of subjects after the first, second and third vaccine doses, respectively. The most common side effects were injection site pain (59%), fatigue (54%) and headache (39%). No anaphylaxis or myocarditis was reported. Three subjects (2%) experienced disease flare. CONCLUSION: In our cohort of paediatric patients with IMID, observed side effects were found to be mild and disease flare rates were found to be low following COVID-19 vaccination.
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COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Niño , Femenino , Adulto Joven , Adolescente , Adulto , Recién Nacido , Masculino , Vacunas contra la COVID-19 , Prueba de COVID-19 , Brote de los Síntomas , SARS-CoV-2 , Vacunación , Anticuerpos AntiviralesRESUMEN
OBJECTIVES: Immunosuppressed paediatric patients with rheumatic disease (RD) may be at risk for severe or critical disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data remain scarce on coronavirus disease 2019 (COVID-19) outcomes in paediatric RD patients. The aim of this study was to determine the seroprevalence of SARS-CoV-2 IgG and to describe COVID-19 outcomes in immunosuppressed paediatric RD patients. METHODS: Patients diagnosed with RD before age 18 years and treated with at least one immunosuppressive medication for at least 3 months were enrolled from a tertiary paediatric rheumatology practice in New York and also underwent routine SARS-CoV-2 IgG testing from May to November 2020. A total of 571 patients were screened and 262 were enrolled. SARS-CoV-2 IgG-positive subjects were assessed for symptoms of COVID-19 infection. SARS-CoV-2 PCR results were recorded where available. Demographic, diagnostic, medication and outcome data were collected. RESULTS: Of 262 subjects (186 female), 35 (13%) were SARS-CoV-2 IgG positive; 17 (49%) had symptoms suggestive of COVID-19. Of the 17 patients who had SARS-CoV-2 PCR testing, 11 (65%) were PCR positive, 7 of whom were IgG positive. Most SARS-CoV-2 IgG-positive subjects were not PCR tested. The most common symptoms in IgG- and/or PCR-positive subjects were fever, fatigue and cough. No SARS-CoV-2 IgG- or PCR-positive subject developed severe or critical COVID-19 or required hospitalization. CONCLUSIONS: This is the first report of clinical outcomes of SARS-CoV-2 infection and seroprevalence of SARS-CoV-2 IgG in a large cohort of paediatric RD patients. Most SARS-CoV-2 IgG-positive subjects had no symptoms of COVID-19 infection. Symptomatic subjects all had mild COVID-19 symptoms, suggesting that the risk of severe or critical COVID-19 in immunosuppressed paediatric RD patients is minimal.
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COVID-19 , Enfermedades Reumáticas , Adolescente , Anticuerpos Antivirales , COVID-19/epidemiología , Niño , Femenino , Humanos , Inmunoglobulina G , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , SARS-CoV-2 , Estudios SeroepidemiológicosRESUMEN
OBJECTIVE: The OMERACT Juvenile Idiopathic Arthritis (JIA) Working Group (WG) aimed to reach agreement on a consensus-based definition and description of the core domain related to patient perception of overall well-being and disease activity. METHODS: A committee of patient research partners, clinicians, methodologists, and researchers drafted working definitions and descriptions. The WG conducted two iterative electronic stakeholder surveys to obtain consensus on domain description, definition, and the distinction between patient perception of overall well-being and disease activity. These definitions were then presented at the OMERACT 2023 Special Interest Group (SIG) session for agreement. RESULTS: Forty-five participants, from 7 countries and 4 continents, were comprised of six patients, 18 caregivers, and 21 healthcare providers. The consensus threshold (70%) was exceeded on all survey questions from both stakeholder groups (patients/caregivers, all others). Agreement was obtained on the new definition, description, and domain title, along with agreement on separate assessments of two target domains, patient perception of overall well-being as it relates to disease and patient perception of disease activity. CONCLUSION: Through an iterative consensus process and achieving agreement from the OMERACT SIG session attendees, the JIA WG has created a detailed definition and description for the two target domains in the patient perception of overall well-being related to disease core domain of the JIA mandatory core domain set. The next phase of this work will be instrument selection using the OMERACT filter 2.2.
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Artritis Juvenil , Reumatología , Humanos , Evaluación de Resultado en la Atención de Salud , Consenso , PercepciónRESUMEN
Introduction: The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to 80% by the end of 2023. Methods: Twenty-three hospitals participate in PR-COIN, with over 7,200 active patients with JIA. The disease activity outcome measures include active joint count, physician global assessment of disease activity, and measures related to validated composite disease activity scoring systems including inactive or low disease activity by the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10), inactive or low disease activity by cJADAS10 at 6 months post-diagnosis, mean cJADAS10 score, and the American College of Rheumatology (ACR) provisional criteria for clinical inactive disease. Data is collated to measure network performance, which is displayed on run and control charts. Network-wide interventions have included pre-visit planning, shared decision making, self-management support, population health management, and utilizing a Treat to Target approach to care. Results: Five outcome measures related to disease activity have demonstrated significant improvement over time. The percent of patients with inactive or low disease activity by cJADAS10 surpassed our goal with current network performance at 81%. Clinical inactive disease by ACR provisional criteria improved from 46% to 60%. The mean cJADAS10 score decreased from 4.3 to 2.6, and the mean active joint count declined from 1.5 to 0.7. Mean physician global assessment of disease activity significantly improved from 1 to 0.6. Conclusions: PR-COIN has shown significant improvement in disease activity metrics for patients with JIA. The network will continue to work on both site-specific and collaborative efforts to improve outcomes for children with JIA with attention to health equity, severity adjustment, and data quality.
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PURPOSE OF REVIEW: To present a case-based approach of three common scenarios which often present to the primary care physician. The approach to these cases and the differential diagnosis are discussed for these common rheumatologic diseases. RECENT FINDINGS: Numerous healthy children and adolescents are referred to pediatric rheumatologists for the evaluation of suspected rheumatologic diseases. Often, general rheumatologic laboratory tests are sent which are not necessarily specific to the clinical situation. There is a high false-positive rate associated with many of these tests and undue anxiety and referrals result from these. Directed laboratory studies based on history and exam findings are more prudent and useful in the evaluation of these children. Routine antinuclear antibody testing, for example, is not recommended without supportive symptoms or signs. SUMMARY: A practical approach for primary care physicians is described for the evaluation of patients suspected of having some of the more common pediatric rheumatologic symptoms and diseases.
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Enfermedades Reumáticas/diagnóstico , Artritis Infecciosa/diagnóstico , Artritis Juvenil/diagnóstico , Niño , Diagnóstico Diferencial , Fiebre Mediterránea Familiar/diagnóstico , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Examen Físico/métodos , Atención Primaria de Salud/métodosRESUMEN
OBJECTIVE: To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. METHODS: Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. RESULTS: By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (χ(2) = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events. CONCLUSION: Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms.
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Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Metotrexato/uso terapéutico , Prednisolona/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Adolescente , Antirreumáticos/administración & dosificación , Niño , Preescolar , Método Doble Ciego , Esquema de Medicación , Etanercept , Femenino , Humanos , Inmunoglobulina G/administración & dosificación , Estudios Longitudinales , Masculino , Metotrexato/administración & dosificación , Prednisolona/administración & dosificación , Estudios Prospectivos , Receptores del Factor de Necrosis Tumoral/administración & dosificación , Inducción de Remisión , Resultado del TratamientoRESUMEN
OBJECTIVE: To describe the selection, development, and implementation of quality measures (QMs) for juvenile idiopathic arthritis (JIA) by the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN), a multihospital learning health network using quality improvement methods and leveraging QMs to drive improved outcomes across a JIA population since 2011. METHODS: An American College of Rheumatology-endorsed multistakeholder process previously selected initial process QMs. Clinicians in PR-COIN and parents of children with JIA collaboratively selected outcome QMs. A committee of rheumatologists and data analysts developed operational definitions. QMs were programmed and validated using patient data. Measures are populated by registry data, and performance is displayed on automated statistical process control charts. PR-COIN centers use rapid-cycle quality improvement approaches to improve performance metrics. The QMs are revised for usefulness, to reflect best practices, and to support network initiatives. RESULTS: The initial QM set included 13 process measures concerning standardized measurement of disease activity, collection of patient-reported outcome assessments, and clinical performance measures. Initial outcome measures were clinical inactive disease, low pain score, and optimal physical functioning. The revised QM set has 20 measures and includes additional measures of disease activity, data quality, and a balancing measure. CONCLUSION: PR-COIN has developed and tested JIA QMs to assess clinical performance and patient outcomes. The implementation of robust QMs is important to improve quality of care. PR-COIN's set of JIA QMs is the first comprehensive set of QMs used at the point-of-care for a large cohort of JIA patients in a variety of pediatric rheumatology practice settings.
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Antirreumáticos , Artritis Juvenil , Reumatología , Humanos , Niño , Artritis Juvenil/terapia , Artritis Juvenil/tratamiento farmacológico , Reumatología/métodos , Antirreumáticos/uso terapéutico , Indicadores de Calidad de la Atención de Salud , Evaluación de Resultado en la Atención de SaludRESUMEN
Juvenile idiopathic arthrithis (JIA) is the most common rheumatic disease of childhood.JIA is a chronic disease that is associated with periods of disease flares and periods of disease inactivity.Early, aggressive treatment with nonsteroidal anti-inflammatory drugs, intra-articular corticosteroid injections, or methotrexate, has significantly improved the outcome of most children who have JIA. Biologics have been shown to be both safe and effective for the treatment of more aggressive forms of arthritis and for uveitis. Long-term safety data of biologics is still uncertain. In the near future, it is hoped that genetic testing will allow earlier diagnosis of JIA as well as help predict the disease course of children who have JIA. Genetic analysis also may allow physicians to target therapies more effectively. It is hoped that development of more specific therapies will decrease overall immunosuppression and other associated toxicities.
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Artritis Juvenil , Antiinflamatorios no Esteroideos/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/complicaciones , Artritis Juvenil/diagnóstico , Artritis Juvenil/fisiopatología , Artritis Juvenil/terapia , Artritis Psoriásica/diagnóstico , Niño , Humanos , Iritis/diagnóstico , Iritis/etiología , Grupo de Atención al Paciente , Pronóstico , Trasplante de Células MadreRESUMEN
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.
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Antirreumáticos/uso terapéutico , Artritis Juvenil/sangre , Artritis Juvenil/tratamiento farmacológico , Calgranulina A/sangre , Calgranulina B/sangre , Proteína S100A12/sangre , Adolescente , Biomarcadores/sangre , Niño , Preescolar , Femenino , Humanos , Quimioterapia de Mantención/métodos , Masculino , Brote de los Síntomas , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Privación de TratamientoRESUMEN
OBJECTIVE: Nonadherence is currently an underrecognized and potentially modifiable obstacle to care in juvenile idiopathic arthritis (JIA). The purpose of our study was to design and implement a standardized approach to identifying adherence barriers for youth with JIA across 7 pediatric rheumatology clinics through the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) and to assess the frequency of adherence barriers in patients and their caregivers across treatment modalities. METHODS: An iterative process using coproduction among parents and providers of patients with JIA was used to design the Barriers Assessment Tool to screen for adherence barriers across 4 treatment modalities (i.e., oral medications, injectable medications, infusions, and physical/occupational therapy). This tool was implemented in 7 rheumatology clinics across the United States and patient responses were collected for analysis. RESULTS: Data were collected from 578 parents and 99 patients (n = 44 parent-child dyads). Seventy-seven percent (n = 444) of caregivers and 70% (n = 69) of patients reported at least 1 adherence barrier across all treatment components. The most commonly reported adherence barriers included worry about future consequences of therapy, pain, forgetting, side effects, and embarrassment related to the therapy. There was no significant difference between endorsement of barriers between parents and adolescents. CONCLUSION: Implementing a standardized tool assessing adherence barriers in the JIA population across multiple clinical settings is feasible. Systematic screening sheds light on the factors that make adherence difficult in JIA and identifies targets for future adherence interventions in clinical practice.
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Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Cumplimiento de la Medicación/psicología , Artritis Juvenil/psicología , Femenino , Humanos , Masculino , Padres , Encuestas y CuestionariosRESUMEN
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.
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Antirreumáticos/inmunología , Artritis Juvenil/sangre , Autoanticuerpos/sangre , Proteínas Cromosómicas no Histona/inmunología , Proteínas Oncogénicas/inmunología , Proteínas de Unión a Poli-ADP-Ribosa/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/inmunología , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Brote de los Síntomas , Privación de TratamientoRESUMEN
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.
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Antirreumáticos/administración & dosificación , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/patología , Quimioterapia de Inducción/estadística & datos numéricos , Privación de Tratamiento/estadística & datos numéricos , Adolescente , Niño , Preescolar , Quimioterapia Combinada , Femenino , Humanos , Lactante , Tablas de Vida , Masculino , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Brote de los Síntomas , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
OBJECTIVE: To identify targets for improving mental healthcare of adolescents with systemic lupus erythematosus (SLE) by assessing current practices and perceived barriers for mental health intervention by pediatric rheumatology clinicians. METHODS: Members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed a Web-based survey assessing current mental health practices, beliefs, and barriers. We examined associations between provider characteristics and the frequency of barriers to mental health screening and treatment using multivariable linear regression. RESULTS: Of the 375 eligible CARRA members, 130 responded (35%) and 119 completed the survey. Fifty-two percent described identification of depression/anxiety in adolescents with SLE at their practice as inadequate, and 45% described treatment as inadequate. Seventy-seven percent stated that routine screening for depression/anxiety in pediatric rheumatology should be conducted, but only 2% routinely used a standardized instrument. Limited staff resources and time were the most frequent barriers to screening. Respondents with formal postgraduate mental health training, experience treating young adults, and practicing at sites with very accessible mental health staff, in urban locations, and in Canada reported fewer barriers to screening. Long waitlists and limited availability of mental health providers were the most frequent barriers to treatment. Male clinicians and those practicing in the Midwest and Canada reported fewer barriers to treatment. CONCLUSION: Pediatric rheumatology clinicians perceive a need for improved mental healthcare of adolescents with SLE. Potential strategies to overcome barriers include enhanced mental health training for pediatric rheumatologists, standardized rheumatology-based mental health practices, and better integration of medical and mental health services.
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Servicios de Salud del Adolescente/normas , Lupus Eritematoso Sistémico/psicología , Trastornos Mentales/terapia , Servicios de Salud Mental/normas , Mejoramiento de la Calidad , Reumatología/normas , Adolescente , Canadá , Encuestas de Atención de la Salud , Humanos , Tamizaje Masivo , Trastornos Mentales/psicología , Pautas de la Práctica en Medicina , Estados UnidosRESUMEN
OBJECTIVE: To follow children with juvenile idiopathic arthritis (JIA) who had completed at least 6 months of the TRial of Early Aggressive Therapy (TREAT) clinical study for an additional 2 years, describing safety of early aggressive treatment, disease activity, function, and duration of clinical inactive disease (CID) during followup. METHODS: Children were treated as per provider's discretion. Physician, patient/parent, and laboratory measures of disease status as well as safety information were collected at clinic visits every 3 months for up to 2 years. RESULTS: Forty-eight children were followed for a mean of 28 months (range 12-42) beyond the end of the TREAT study. Half of patients were in CID for > 50% of their followup time. Overall, 88% of patients achieved CID at > 1 study visit and 54% achieved clinical remission while taking medication. Six patients were in CID for the duration of the study, and, of those, 2 achieved a full year of clinical remission while not taking medication. Active disease was mild: mean physician's global assessment 2.4, active joint count 3.5, parent global evaluation 2.4, Childhood Health Assessment Questionnaire 0.32, erythrocyte sedimentation rate 19 mm/h, and morning stiffness 23 min. There were no serious adverse events or adverse events reported at grade 3 or higher of Common Terminology Criteria for Adverse Events. CONCLUSION: Early aggressive therapy in this cohort of patients with polyarticular JIA who had high initial disease activity was associated with prolonged periods of CID in the majority of patients during followup. Those not in CID had low levels of disease activity.
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Artritis Juvenil/diagnóstico , Artritis Juvenil/tratamiento farmacológico , Evaluación de la Discapacidad , Inmunoglobulina G/uso terapéutico , Metotrexato/uso terapéutico , Prednisolona/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Artritis Juvenil/sangre , Sedimentación Sanguínea , Niño , Quimioterapia Combinada , Etanercept , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Estudios Prospectivos , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
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.
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Antiinflamatorios no Esteroideos , Artritis Juvenil/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Pirazoles/efectos adversos , Sulfonamidas/efectos adversos , Adolescente , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/clasificación , Celecoxib , Niño , Preescolar , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Humanos , Masculino , Administración del Tratamiento Farmacológico , Seguridad del Paciente , Pirazoles/administración & dosificación , Sistema de Registros , Sulfonamidas/administración & dosificación , Tiempo , Estados UnidosRESUMEN
OBJECTIVE: To determine the elapsed time while receiving aggressive therapy to the first observation of clinically inactive disease (CID), total duration of CID and potential predictors of this response in a cohort of children with recent onset of polyarticular juvenile idiopathic arthritis (poly-JIA). METHODS: Eighty-five children were randomized blindly to methotrexate (MTX), etanercept, and rapidly tapered prednisolone (MEP) or MTX monotherapy and assessed for CID over 1 year of treatment. Patients who failed to achieve intermediary endpoints were switched to open-label MEP treatment. RESULTS: Fifty-eight (68.2%) of the 85 patients achieved CID at 1 or more visits including 18 who received blinded MEP, 11 while receiving MTX monotherapy, and 29 while receiving open-label MEP. Patients starting on MEP achieved CID earlier and had more study days in CID compared to those starting MTX, but the differences were not significantly different. Patients given MEP (more aggressive therapy) earlier in the disease course were statistically more likely to have a higher proportion of followup visits in CID than those with longer disease course at baseline. Those who achieved American College of Rheumatology Pediatric 70 response at 4 months had a significantly greater proportion of followup visits in CID, compared to those who failed to achieve this improvement (p < 0.0001). Of the 32 patients who met criteria for CID and then lost CID status, only 3 fulfilled the definition of disease flare. CONCLUSION: Shorter disease duration prior to treatment, a robust response at 4 months, and more aggressive therapy result in a higher likelihood and longer duration of CID in patients with poly-JIA. The original trial from which data for this analysis were obtained is registered on www.clinicaltrials.gov NCT 00443430.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Metotrexato/uso terapéutico , Prednisolona/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Adolescente , Niño , Preescolar , Progresión de la Enfermedad , Método Doble Ciego , Quimioterapia Combinada , Etanercept , Femenino , Humanos , Masculino , Inducción de Remisión , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. METHODS: An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in ≥2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary end point was time to response, using the adapted American College of Rheumatology Pediatric 30 criteria coupled with the absence of fever and taper of the dosage of systemic corticosteroids, using prespecified criteria. RESULTS: The time to response was shorter in the rilonacept arm than in the placebo arm (χ(2) = 7.235, P = 0.007). The secondary analysis, which used the same response criteria, showed that 20 (57%) of 35 patients in the rilonacept arm had a response at week 4 compared with 9 (27%) of 33 patients in the placebo arm (P = 0.016). Exacerbation of systemic juvenile idiopathic arthritis (JIA) was the most common severe adverse event. More patients in the rilonacept arm had elevated liver transaminase levels (including levels more than 3 times the upper limit of normal) compared with those in the placebo arm. Adverse events were similar in the 2 arms of the study. CONCLUSION: Rilonacept was generally well tolerated and demonstrated efficacy in active systemic JIA.