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OBJECTIVE: To describe risk factors for IBD development in a cohort of children with JIA. METHODS: JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different DMARDs were calculated, and differences between therapies were expressed as relative risks (RR). RESULTS: Out of 8942 patients, 48 (0.54% ) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were enthesitis-related arthritis [odds ratio (OR): 3.68, 95% CI: 1.41, 9.40] and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12, 4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99, 29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42, 22.77) and infliximab (RR: 7.61, 95% CI: 1.27, 45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15, 13.89). CONCLUSION: IBD in JIA was associated with enthesitis-related arthritis and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use.
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Antirreumáticos , Artritis Juvenil , Enfermedades Inflamatorias del Intestino , Antirreumáticos/efectos adversos , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/epidemiología , Niño , Etanercept/efectos adversos , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/epidemiología , Masculino , Metotrexato/uso terapéutico , Sistema de RegistrosRESUMEN
OBJECTIVES: To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA). METHODS: In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or <30 kg, respectively. Primary end points were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with i.v. tocilizumab (i.v.-TCZ) in sJIA and pJIA. RESULTS: Study participants were 51 sJIA patients and 52 pJIA patients aged 1-17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ. CONCLUSION: s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Antirreumáticos/administración & dosificación , Artritis Juvenil/tratamiento farmacológico , Artritis/tratamiento farmacológico , Adolescente , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Lactante , Inyecciones Subcutáneas , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE: This report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA). METHODS: In this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0-16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16-48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety. RESULTS: Among 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with <1% of all injections. PK analysis confirmed adequate golimumab dosing for polyJIA. CONCLUSION: Although the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred. CLINICAL TRIAL REGISTRATION: NCT01230827; Results.
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Anticuerpos Monoclonales/administración & dosificación , Antirreumáticos/administración & dosificación , Artritis Juvenil/tratamiento farmacológico , Artritis/tratamiento farmacológico , Metotrexato/administración & dosificación , Adolescente , Artritis/patología , Artritis Juvenil/patología , Niño , Preescolar , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Inducción de Remisión , Brote de los Síntomas , Resultado del TratamientoRESUMEN
The aim of this study was to validate the paediatric Gait, Arms, Legs, Spine (pGALS) tool for Mexican Spanish to screen Mexican paediatric population for musculoskeletal (MSK) disorders. A cross-sectional study was performed in the Paediatric Hospital of the Mexican Social Security Institute in Guadalajara, Jalisco. The validation included children and adolescents aged 6-16 years, 87 patients with musculoskeletal disorders and 88 controls without musculoskeletal disorders. The cross-cultural validation followed the current published guidelines. The average pGALS administration time was 2.9 min (SD 0.54). The internal consistency score (Cronbach's α) was 0.90 (0.89 for inflammatory and 0.77 for non-inflammatory disorders) for MSK disorders, with a sensitivity of 97 % (95 % CI 92-99 %), a specificity of 93 % (95 % CI 86-97 %), a LR+ of 14.3, and a ROC curve of 0.95 (95 % CI 0.92-0.98 %). The inflammatory disorders group had a sensitivity of 97 % (95 % CI 86-99 %), a specificity of 93 % (95 % CI 86-97 %), a LR+ of 14.2, and a ROC curve of 0.95 % (95 % CI 0.91-0.99 %). The non-inflammatory disorders group had a sensitivity of 98 % (95 % CI 89-99 %), a specificity of 93 % (95 % CI 86-97 %), and a LR+ of 14.37, with a ROC curve of 0.95 % (95 % CI 0.92-0.98 %). pGALS is a valid screening tool, fast, easy to administer, and useful for detecting musculoskeletal disorders in Mexican children and adolescents.
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Características Culturales , Marcha , Extremidad Inferior/fisiopatología , Enfermedades Musculoesqueléticas/diagnóstico , Columna Vertebral/fisiopatología , Encuestas y Cuestionarios , Extremidad Superior/fisiopatología , Adolescente , Factores de Edad , Área Bajo la Curva , Estudios de Casos y Controles , Niño , Estudios Transversales , Femenino , Humanos , Masculino , México/epidemiología , Enfermedades Musculoesqueléticas/etnología , Enfermedades Musculoesqueléticas/fisiopatología , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los Resultados , TraducciónRESUMEN
OBJECTIVE: To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). METHODS: This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6â months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4â weeks (8 or 10â mg/kg for body weight (BW) <30â kg; 8â mg/kg for BW ≥30â kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. RESULTS: In part 1, 188 patients received tocilizumab (<30â kg: 10â mg/kg (n=35) or 8â mg/kg (n=34); ≥30â kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: -0.21; 95% CI -0.35 to -0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). CONCLUSIONS: Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. TRIAL REGISTRATION NUMBER: NCT00988221.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Quimioterapia de Mantención/métodos , Receptores de Interleucina-6/antagonistas & inhibidores , Adolescente , Corticoesteroides/uso terapéutico , Bronquitis/inducido químicamente , Celulitis (Flemón)/inducido químicamente , Niño , Preescolar , Progresión de la Enfermedad , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Neumonía/inducido químicamente , Inducción de Remisión/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the noise levels of different areas responsible for newborn care, develop intervention strategies to decrease the noise, and evaluate its effectiveness. METHODS: Prospective, observational and longitudinal study carried out using a sonometer, measuring sound levels for three weeks in the neonatal intensive care unit (NICU), neonatal intermediate care unit (UCIREN), delivery (TOCO QX) and nursery (CUNERO) units. We implemented an intervention program and subsequent measurements were performed under the same initial conditions. RESULTS: When comparing the decibel levels in different areas during the three weeks, pre- and post-intervention, we found at the neonatal intensive care unit 59.9±4.8 vs. 56.4±4.7 dB (p<0.001), neonatal intermediate care unit 55.3±3.9 vs. 51.3±4.4 dB (p<0.001), delivery unit 57.3±4.6 vs. 57.3±5.5 dB (NS), and nursery unit 57.6±5.8 vs. 53.9±5.8 dB (p<0.001). CONCLUSIONS: There was a significant reduction in noise levels of 3.5 dB at the NICU, 4 dB at UCIREN and 3.7 dB at TOCO QX, so the intervention program was effective in these areas; however, the decibel levels registered continue above those recommended by international standards.
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Exposición a Riesgos Ambientales/prevención & control , Monitoreo del Ambiente/métodos , Ruido/prevención & control , Exposición a Riesgos Ambientales/análisis , Ambiente de Instituciones de Salud , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Estudios Longitudinales , Estudios Prospectivos , Centros de Atención TerciariaRESUMEN
Hematogenous spread of Neisseria gonorrhoeae, a sexually transmitted pathogen, results in disseminated gonococcal disease (DGD), also known as arthritis-dermatitis syndrome, due to the development of skin lesions, tenosynovitis, and arthritis. The most frequently affected population is young adults. We describe the case of an adolescent female who acutely developed skin lesions, arthritis, tenosynovitis, and constitutional symptoms. The causal agent was identified by a culture of vaginal secretion and treated with ceftriaxone for 7 days with complete recovery. It is important to differentiate this clinical picture from other types of arthritis developed in adolescence.
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Artritis Infecciosa , Gonorrea , Tenosinovitis , Adolescente , Adulto Joven , Humanos , Femenino , Niño , Tenosinovitis/complicaciones , Antibacterianos/uso terapéutico , Gonorrea/complicaciones , Gonorrea/diagnóstico , Gonorrea/tratamiento farmacológico , Neisseria gonorrhoeae , Artritis Infecciosa/diagnósticoRESUMEN
OBJECTIVE: To describe the efficacy and safety data of children with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with abatacept (ABA) + methotrexate (MTX) or ABA monotherapy when prior MTX use was either ineffective or not tolerated. METHODS: Posthoc analysis of 2 phase III trials of subcutaneous (SC) and intravenous (IV) ABA over 2 years in patients with pcJIA (aged 2-17 years). Patients were stratified by treatment with ABA + MTX or ABA monotherapy and further by prior biologic use. Efficacy outcomes included JIA-American College of Rheumatology (JIA-ACR) responses, Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein (JADAS27-CRP), and safety. Descriptive pharmacokinetic analyses were also performed. RESULTS: Efficacy responses (JIA-ACR and JADAS27-CRP) were similar between patients receiving ABA + MTX (n = 310) or ABA monotherapy (n = 99) and persisted over 2 years. Clinical response rates were similar in biologic-naïve patients and prior biologic users; this was independent of MTX use. Across both studies, ABA + MTX and ABA monotherapy displayed similar safety profiles. Pharmacokinetic results revealed similar minimum steady-state trough ABA concentrations between studies. Further, baseline MTX did not influence ABA clearance and was not a significant predictor of JIA-ACR responses. CONCLUSION: ABA monotherapy (SC and IV) was effective and well tolerated in children with pcJIA when prior MTX use was ineffective or not tolerated. Treatment effects of ABA appear to be independent of MTX coadministration. Consequently, ABA monotherapy can be considered for those with prior biologic therapy if MTX use is inappropriate. (ClinicalTrials.gov: NCT01844518 and NCT00095173).
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Antirreumáticos , Artritis Juvenil , Productos Biológicos , Niño , Humanos , Metotrexato/uso terapéutico , Abatacept/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/inducido químicamente , Antirreumáticos/efectos adversos , Quimioterapia Combinada , Productos Biológicos/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: Describe the distribution of adult and pediatric rheumatologists with current certification in Mexico and the factors associated with this distribution. METHODS: The databases of the Mexican Council of Rheumatology and the Mexican College of Rheumatology for 2020 were reviewed. The rate of rheumatologists per 100,000 inhabitants by state of the Mexican Republic was calculated. To find out the number of inhabitants by state, the results of the 2020 population census of the National Institute of Statistics and Geography were consulted. The number of rheumatologists with current certification by state, age, and sex was analyzed. RESULTS: In Mexico, there are 1002 registered adult rheumatologists with a mean age of 48.12⯱â¯13 years. The male gender prevailed with a ratio of 1.18:1. Ninety-four pediatric rheumatologists were identified with a mean age of 42.25⯱â¯10.4 years, with a predominance of the female gender with a ratio of 2.2:1. In Mexico City and Jalisco, more than one rheumatologist/100,000 inhabitants were reported in the specialty of adults and only in Mexico City in pediatrics. The current certification is 65%-70% on average and the factors associated with a higher prevalence were younger age, female gender and geographic location. CONCLUSIONS: There is a shortage of rheumatologists in Mexico and in the pediatric area there are underserved regions. It is important that health policies apply measures that allow a more balanced and efficient regionalization of this specialty. Although most rheumatologists have current certification, it is necessary to establish strategies to increase this proportion.
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Reumatólogos , Reumatología , Adulto , Humanos , Masculino , Femenino , Niño , Persona de Mediana Edad , México , Certificación , Bases de Datos FactualesRESUMEN
OBJECTIVES: To describe the design process of a medical care program for adolescents with pediatric onset rheumatic diseases (PRD) during the transition from pediatric to adult care in a resource-constrained hospital. METHODS: The model of attention was developed in three steps: 1) the selection of a multidisciplinary team, 2) the evaluation of the state of readiness of patients and caregivers for the transition, and 3) the design of a strategy of attention according to local needs. The results of the first two steps were used in order to develop the strategy of attention. RESULTS: The transition process was structured in three stages: pretransition (at pediatric rheumatology clinic), Transition Clinic for Adolescents with Rheumatic Diseases (TCARD, the main intervention), and post-transition (at adult rheumatology clinic). Each stage was divided, in turn, into a variable number of phases (8 in total), which included activities and goals that patients and caregivers were to accomplish during the process. A multidisciplinary approach was planned by pediatric and adult rheumatologists, nutritionists, physiatrists, psychiatrist, psychologist, nurse, and social worker. During TCARD, counseling, education, nutritional, physical, and mental health interventions were considered. CONCLUSIONS: The proposed transition model for patients with rheumatic diseases can be a useful tool in developing countries.
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Enfermedades Reumáticas , Reumatología , Transición a la Atención de Adultos , Adulto , Adolescente , Humanos , Niño , Reumatología/métodos , Enfermedades Reumáticas/terapia , Instituciones de Atención AmbulatoriaRESUMEN
BACKGROUND: Etanercept (ETN) and adalimumab (ADA) are considered equally effective biologicals in the treatment of arthritis in juvenile idiopathic arthritis (JIA) but no studies have compared their impact on patient-reported well-being. The objective of this study was to determine whether ETN and ADA have a differential effect on patient-reported well-being in non-systemic JIA using real-world data. METHODS: Biological-naive patients without a history of uveitis were selected from the international Pharmachild registry. Patients starting ETN were matched to patients starting ADA based on propensity score and outcomes were collected at time of therapy initiation and 3-12 months afterwards. Primary outcome at follow-up was the improvement in Juvenile Arthritis Multidimensional Assessment Report (JAMAR) visual analogue scale (VAS) well-being score from baseline. Secondary outcomes at follow-up were decrease in active joint count, adverse events and uveitis events. Outcomes were analyzed using linear and logistic mixed effects models. RESULTS: Out of 158 eligible patients, 45 ETN starters and 45 ADA starters could be propensity score matched resulting in similar VAS well-being scores at baseline. At follow-up, the median improvement in VAS well-being was 2 (interquartile range (IQR): 0.0 - 4.0) and scores were significantly better (P = 0.01) for ETN starters (median 0.0, IQR: 0.0 - 1.0) compared to ADA starters (median 1.0, IQR: 0.0 - 3.5). The estimated mean difference in VAS well-being improvement from baseline for ETN versus ADA was 0.89 (95% CI: -0.01 - 1.78; P = 0.06). The estimated mean difference in active joint count decrease was -0.36 (95% CI: -1.02 - 0.30; P = 0.28) and odds ratio for adverse events was 0.48 (95% CI: 0.16 -1.44; P = 0.19). One uveitis event was observed in the ETN group. CONCLUSIONS: Both ETN and ADA improve well-being in non-systemic JIA. Our data might indicate a trend towards a slightly stronger effect for ETN, but larger studies are needed to confirm this given the lack of statistical significance.
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Antirreumáticos , Artritis Juvenil , Uveítis , Humanos , Etanercept/efectos adversos , Adalimumab/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Estudios de Cohortes , Puntaje de Propensión , Uveítis/tratamiento farmacológico , Uveítis/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with juvenile chronic inflammatory systemic diseases (jCID) are vulnerable to many circumstances when transitioning to adult-centered healthcare; this increases the burden of disease and worsen their quality of life. METHODS: MEDLINE, Embase, Web of Science and Scopus were searched from inception to March 16th, 2021. We included observational, randomized controlled trials and quasi-experimental studies that evaluated a transitional care program for adolescents and young adults with jCIDs. We extracted information regarding health-related quality of life, disease activity, drop-out rates, clinical attendance rates, hospital admission rates, disease-related knowledge, surgeries performed, drug toxicity and satisfaction rates. RESULTS: Fifteen studies met our inclusion criteria. The implementation of transition programs showed a reduction on hospital admission rates for those with transition program (OR 0.28; 95% CI 0.13 to 0.61; I 2 = 0%; p = 0.97), rates of surgeries performed (OR 0.26; 95% CI 0.12 to 0.59; I 2 = 0%; p = 0.50) and drop-out rates from the adult clinic (OR 0.23; 95% CI 0.12 to 0.46; I 2 = 0%; p = 0.88). No differences were found in other outcomes. CONCLUSION: The available body of evidence supports the implementation of transition programs as it could be a determining factor to prevent hospital admission rates, surgeries needed and adult clinic attendance rates.
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Enfermedades Autoinmunes/terapia , Costo de Enfermedad , Calidad de Vida , Enfermedades Reumáticas/terapia , Cuidado de Transición , Adolescente , Adulto , Niño , Enfermedad Crónica/terapia , Fibrosis Quística/terapia , Diabetes Mellitus/terapia , Humanos , Síndrome del Colon Irritable/terapia , Adulto JovenRESUMEN
OBJECTIVE: We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study. METHODS: This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >or=21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008. RESULTS: Of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient. CONCLUSION: Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.
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Artritis Juvenil/tratamiento farmacológico , Inmunoconjugados/efectos adversos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Abatacept , Adolescente , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Niño , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Humanos , Inmunoconjugados/uso terapéutico , Metotrexato/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Multisystem inflammatory syndrome in children (MIS-C) is an emerging entity during the coronavirus disease 2019 pandemic. Medium- and large-vessel changes are present in MIS-C; however, microcirculatory impairment has not been documented. We report a case of MIS-C in a toddler that presented with persistent fever, gastrointestinal symptoms and rash. Nailfold videocapillaroscopy was abnormal, suggesting microcirculatory disease in the setting of MIS-C.
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COVID-19/diagnóstico , Enfermedades Gastrointestinales/diagnóstico , SARS-CoV-2/aislamiento & purificación , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , COVID-19/fisiopatología , COVID-19/virología , Exantema , Fiebre , Enfermedades Gastrointestinales/fisiopatología , Enfermedades Gastrointestinales/virología , Humanos , Lactante , Masculino , México , Microcirculación , Angioscopía Microscópica , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Síndrome de Respuesta Inflamatoria Sistémica/virologíaRESUMEN
BACKGROUND: Juvenile Idiopathic Arthritis (JIA) requires complex care that generate elevated costs, which results in a high economic impact for the family. The aim of this systematic review was to collect and cluster the information currently available on healthcare costs associated with JIA after the introduction of biological therapies. METHODS: We comprehensively searched in MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Databases for studies from January 2000 to March 2021. Reviewers working independently and in duplicate appraised the quality and included primary studies that report total, direct and/or indirect costs related to JIA for at least one year. The costs were converted to United States dollars and an inflationary adjustment was made. RESULTS: We found 18 eligible studies including data from 6,540 patients. Total costs were reported in 10 articles, ranging from $310 USD to $44,832 USD annually. Direct costs were reported in 16 articles ($193 USD to $32,446 USD), showing a proportion of 55 to 98 % of total costs. Those costs were mostly related to medications and medical appointments. Six studies reported indirect costs ($117 USD to $12,385 USD). Four studies reported costs according to JIA category observing the highest in polyarticular JIA. Total and direct costs increased up to three times after biological therapy initiation. A high risk of reporting bias and inconsistency of the methodology used were found. CONCLUSION: The costs of JIA are substantial, and the highest are derived from medication and medical appointments. Indirect costs of JIA are underrepresented in costs analysis.
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Artritis Juvenil/economía , Costo de Enfermedad , Costos de la Atención en Salud , Análisis Costo-Beneficio , HumanosRESUMEN
BACKGROUND: Pediatric rheumatic disease (PRD) patients and their caregivers face a number of challenges, including the consequences of the PRD in patients and the impact on multiple dimensions of the caregivers' daily lives. The objective of this study is to measure the economic, psychological and social impact that PRD has on the caregivers of Mexican children. METHODS: This is a multicenter, cross-sectional study including primary caregivers of children and adolescents with PRD (JIA, JDM and JSLE) during April and November, 2019. A trained interviewer conducted the CAREGIVERS questionnaire, a specific, 28-item multidimensional tool validated to measure the impact on different dimensions of the lives of caregivers. Sociodemographic, clinical, and healthcare system data were collected for further analysis. RESULTS: Two hundred participants were recruited (women 169, 84.5%, aged 38 [IQR 33-44] years); 109 (54.5%) cared for patients with JIA, 28 (14%) JDM and 63 (31.5%) JSLE. The healthcare system was found to be determinant on the impact of the disease. The emotional impact was higher in all the participants, regardless of the specific diagnoses. The social dimension showed significant differences regarding PRD, healthcare system, time to reach the center, presence of disability, active disease, cutaneous and systemic manifestations, treatment and partner. Financial and work impacts were more frequent in those caring for JSLE and less so in those with a partner. Family relationships changed in 81 caregivers (25 [12.5%] worsened and 56 [28%] improved). No variables affecting spirituality were found. For caregivers without a partner, the social networks impact increased. CONCLUSION: The influence of sociodemographic factors can be devastating on families with children with a PRD. These data will help physicians to identify the areas with the greatest need for intervention to achieve comprehensive care for caregivers and their patients.
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Cuidadores/economía , Cuidadores/psicología , Costo de Enfermedad , Enfermedades Reumáticas , Adulto , Niño , Estudios Transversales , Femenino , Humanos , Masculino , México , AutoinformeRESUMEN
BACKGROUND: The primary caregiver is an important person in the life of patients with JIA. Their reactions depend on social, emotional and economic factors that affect the therapeutic alliance. Some generic instruments have been used to evaluate burden, anxiety, or quality of life of caregivers. This study aims to develop a specific instrument to measure the psychosocial and economic impacts on primary caregivers of patients with JIA. METHODOLOGY: This is a mixed methods research, that includes qualitative and quantitative data, and was carried out in two phases. First phase: a pragmatic qualitative study (questionnaire construction) was conducted in two parts, a non-systematic literature review followed by interviews with primary caregivers. Second phase: a cross-sectional study (questionnaire validation) to complete validation and estimate Cronbach's alphas based on tetrachoric correlation coefficients, correlation matrix and Cohen's kappa coefficient test. RESULTS: There were 38 articles found related to the experience of caregivers. 15 primary caregivers were interviewed (female 93%, median age 45 years). Thematic analysis identified 9 important topics from the perspective of participants (economic impact, coping, family roles, impact of diagnosis, mental health, couple/mate relationships, impact at work, religion, and knowledge of the disease). These topics were combined to create the interview questionnaire (56 items). Later, it was modified to 62 items that were divided into five dimensions: impact of the disease (psychosocial, economic, family, and relationships), knowledge of the disease, alternative medicine, future, and religion. The interview questionnaire was applied to 32 primary caregivers (female 93%, median age 37 years), results identify depression on 29 (90%), 18 (56%) feel sadness at diagnosis, 20 (63%) mentioned that JIA has influenced in their financial situation, 23 (72%) feel anxiety about the future, and 11 (37%) considered that their family relationships have changed. Statistical analysis identified inconsistencies during convergent and divergent validity of the construct. Consequently, 11 items were eliminated, 3 relocated, 6 modified, and 39 compacted obtaining the "Impact of Pediatric Rheumatic Diseases on Caregivers Multi-assessment Questionnaire" (CAREGIVERS questionnaire). This final version resulted on an eight-dimension (28 items) instrument. CONCLUSIONS: The CAREGIVERS questionnaire captures perspectives of both the participants and clinicians. It will be helpful to measure the impact of the disease and thus, to improve the quality of care of children with JIA and their families.
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Artritis Juvenil/terapia , Cuidadores/psicología , Adolescente , Adulto , Artritis Juvenil/psicología , Cuidadores/estadística & datos numéricos , Niño , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Psicología , Reproducibilidad de los Resultados , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. METHODS: We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. FINDINGS: Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, both in controls (p=0.50). INTERPRETATION: Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. FUNDING: Bristol-Myers Squibb.
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Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Abatacept , Adolescente , Antirreumáticos/efectos adversos , Artritis Juvenil/clasificación , Niño , Método Doble Ciego , Femenino , Humanos , Inmunoconjugados/efectos adversos , Infusiones Intravenosas , Masculino , Rango del Movimiento Articular , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
OBJECTIVE: Evaluate growth in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ) for up to 2 years in a phase III trial. METHODS: Patients with pcJIA lasting at least 6 months and inadequate response to methotrexate received open-label TCZ intravenously every 4 weeks (randomly assigned to 8 or 10 mg/kg if they weighed < 30 kg; received 8 mg/kg if they weighed ≥ 30 kg) for 16 weeks. Patients with JIA American College of Rheumatology 30 response at Week 16 were randomly assigned to TCZ or placebo for 24 weeks, with an open-label extension through Week 104. Mean ± SD height velocity (cm/yr) and World Health Organization (WHO) height SD score (SDS) were measured in patients receiving ≥ 1 dose of TCZ who did not receive growth hormone and in patients whose baseline Tanner stage was ≤ 3. RESULTS: The study included 187 of 188 patients (99.5%) with mean WHO height SDS -0.5 ± 1.2, which was unrelated to age or disease duration (Spearman rank correlations r = 0.08 and r = -0.12, respectively). There were 123 patients at Tanner stage ≤ 3 at baseline, among whom 103 completed the study with 2 years of height SDS data. Mean height SDS increased from baseline to year 2 (+0.40, p < 0.0001). In 74 of 103 patients (72%), height SDS was greater than at baseline, and mean height velocity was 6.7 ± 2.0 cm/year. CONCLUSION: Among patients with pcJIA at Tanner stage ≤ 3 at baseline, 72% (74/103) had increased height SDS at the end of the study.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Estatura/efectos de los fármacos , Desarrollo Infantil/efectos de los fármacos , Adolescente , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antirreumáticos/administración & dosificación , Artritis Juvenil/fisiopatología , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular-course juvenile idiopathic arthritis (JIA). METHODS: In this phase III, open-label, international, multicenter, single-arm study, patients with polyarticular JIA (cohort 1, ages 6-17 years and cohort 2, ages 2-5 years) in whom treatment with ≥1 disease-modifying antirheumatic drug was unsuccessful received weight-tiered SC abatacept weekly: 10 to <25 kg (50 mg), 25 to <50 kg (87.5 mg), ≥50 kg (125 mg). Patients who had met the JIA-American College of Rheumatology 30% improvement criteria (achieved a JIA-ACR 30 response) at month 4 were given the option to continue SC abatacept to month 24. The primary end point was the abatacept steady-state serum trough concentration (Cminss ) in cohort 1 at month 4. Other outcome measures included JIA-ACR 30, 50, 70, 90, 100, and inactive disease status, the median Juvenile Arthritis Disease Activity Score in 71 joints using the C-reactive protein level (JADAS-71-CRP) over time, safety, and immunogenicity. RESULTS: The median abatacept Cminss at month 4 (primary end point) and at month 24 was above the target therapeutic exposure (10 µg/ml) in both cohorts. The percentage of patients who had achieved JIA-ACR 30, 50, 70, 90, or 100 responses or had inactive disease responses at month 4 (intent-to-treat population) was 83.2%, 72.8%, 52.6%, 28.3%, 14.5%, and 30.1%, respectively, in cohort 1 (n = 173) and 89.1%, 84.8%, 73.9%, 58.7%, 41.3%, and 50.0%, respectively, in cohort 2 (n = 46); the responses were maintained to month 24. The median (interquartile range) JADAS-71-CRP improved from baseline to month 4: cohort 1, from 21.0 (13.5, 30.3) to 4.6 (2.1, 9.4); cohort 2, from 18.1 (14.0, 23.1) to 2.1 (0.3, 4.4). Improvements were sustained to month 24, at which time 27 of 173 patients (cohort 1) and 11 of 22 patients (cohort 2) had achieved JADAS-71-CRP remission. No unexpected adverse events were reported; 4 of 172 patients (2.3%) in cohort 1 and 4 of 46 (8.7%) in cohort 2 developed anti-abatacept antibodies, with no clinical effects. CONCLUSION: Weight-stratified SC abatacept yielded target therapeutic exposures across age and weight groups, was well tolerated, and improved polyarticular JIA symptoms over 24 months.