RESUMEN
BACKGROUND: Juvenile idiopathic arthritis can be refractory to some or all treatment regimens, therefore new medications are needed to treat this population. This trial assessed the efficacy and safety of baricitinib, an oral Janus kinase 1/2-selective inhibitor, versus placebo in patients with juvenile idiopathic arthritis. METHODS: This phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial was conducted in 75 centres in 20 countries. We enrolled patients (aged 2 to <18 years) with polyarticular juvenile idiopathic arthritis (positive or negative for rheumatoid factor), extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, or juvenile psoriatic arthritis, and an inadequate response (after ≥12 weeks of treatment) or intolerance to one or more conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). The trial consisted of a 2-week safety and pharmacokinetic period, a 12-week open-label lead-in period (10 weeks for the safety and pharmacokinetic subcohort), and an up to 32-week placebo-controlled double-blind withdrawal period. After age-based dosing was established in the safety and pharmacokinetic period, patients received a once-daily 4 mg adult-equivalent dose of baricitinib (tablets or suspension) in the open-label lead-in period. Patients meeting Juvenile Idiopathic Arthritis-American College of Rheumatology (JIA-ACR) 30 criteria (JIA-ACR30 responders) at the end of the open-label lead-in (week 12) were eligible for random assignment (1:1) to receive placebo or continue receiving baricitinib, and remained in the double-blind withdrawal period until disease flare or up to the end of the double-blind withdrawal period (week 44). Patients and any personnel interacting directly with patients or sites were masked to group assignment. The primary endpoint was time to disease flare during the double-blind withdrawal period and was assessed in the intention-to-treat population of all randomly assigned patients. Safety was assessed in all patients who received at least one dose of baricitinib throughout the three trial periods. For adverse events in the double-blind withdrawal period, exposure-adjusted incidence rates were calculated. The trial was registered on ClinicalTrials.gov, NCT03773978, and is completed. FINDINGS: Between Dec 17, 2018 and March 3, 2021, 220 patients were enrolled and received at least one dose of baricitinib (152 [69%] girls and 68 [31%] boys; median age 14·0 years [IQR 12·0-16·0]). 219 patients received baricitinib in the open-label lead-in period, of whom 163 (74%) had at least a JIA-ACR30 response at week 12 and were randomly assigned to placebo (n=81) or baricitinib (n=82) in the double-blind withdrawal period. Time to disease flare was significantly shorter with placebo versus baricitinib (hazard ratio 0·241 [95% CI 0·128-0·453], p<0·0001). Median time to flare was 27·14 weeks (95% CI 15·29-not estimable) in the placebo group, and not evaluable for patients in the baricitinib group (<50% had a flare event). Six (3%) of 220 patients had serious adverse events during the safety and pharmacokinetic period or open-label lead-in period. In the double-blind withdrawal period, serious adverse events were reported in four (5%) of 82 patients (incidence rate [IR] 9·7 [95% CI 2·7-24·9] per 100 patient-years at risk) in the baricitinib group and three (4%) of 81 (IR 10·2 [2·1-29·7]) in the placebo group. Treatment-emergent infections were reported during the safety and pharmacokinetic or open-label lead-in period in 55 (25%) of 220 patients, and during the double-blind withdrawal period in 31 (38%) of 82 (IR 102·1 [95% CI 69·3-144·9]) in the baricitinib group and 15 (19%) of 81 (IR 59·0 [33·0-97·3]) in the placebo group. Pulmonary embolism was reported as a serious adverse event in one patient (1%; IR 2·4 [95% CI 0·1-13·3]) in the baricitinib group in the double-blind withdrawal period, which was judged to be related to study treatment. INTERPRETATION: Baricitinib was efficacious with an acceptable safety profile in the treatment of polyarticular juvenile idiopathic arthritis, extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, and juvenile psoriatic arthritis, after inadequate response or intolerance to standard therapy. FUNDING: Eli Lilly and Company under licence from Incyte.
Asunto(s)
Antirreumáticos , Artritis Juvenil , Inhibidores de las Cinasas Janus , Masculino , Adulto , Femenino , Humanos , Adolescente , Artritis Juvenil/tratamiento farmacológico , Brote de los Síntomas , Resultado del Tratamiento , Antirreumáticos/uso terapéutico , Método Doble CiegoRESUMEN
OBJECTIVES: CLIPPER2 was an 8-year, open-label extension of the phase 3b, 2-year CLIPPER study on the safety and efficacy of etanercept in patients with JIA, categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA) or PsA. METHODS: Participants with eoJIA (2-17 years old), ERA or PsA (each 12-17 years old) who received ≥1 etanercept dose (0.8 mg/kg weekly; maximum 50 mg) in CLIPPER could enter CLIPPER2. Primary end point was occurrence of malignancy. Efficacy assessments included proportions achieving JIA ACR 30/50/70/90/100 criteria and ACR inactive disease criteria, and clinical remission (ACR criteria) or Juvenile Arthritis DAS (JADAS) ≤1. RESULTS: Overall, 109/127 (86%) CLIPPER participants entered CLIPPER2 [n = 55 eoJIA, n = 31 ERA, n = 23 PsA; 99 (78%) on active treatment]; 84 (66%) completed 120 months' follow-up [32 (25%) on active treatment]. One malignancy (Hodgkin's disease in 18-year-old patient with eoJIA treated with methotrexate for 8 years) was reported; there were no cases of active tuberculosis or deaths. Numbers and incidence rates (events per 100 patient-years) of TEAEs (excluding infections/ISRs) decreased from 193 (173.81) in Year 1 to 9 (27.15) in Year 10; TE infections and serious infections also decreased. Over 45% of participants (n = 127) achieved JIA ACR50 responses from Month 2 onwards; 42 (33%) and 34 (27%) participants achieved JADAS and ACR clinical remission, respectively. CONCLUSIONS: Etanercept treatment up to 10 years was well tolerated, consistent with the known safety profile, with durable response in the participants still on active treatment. The benefit-risk assessment of etanercept in these JIA categories remains favourable. TRIAL REGISTRATION: ClinicalTrials.gov IDs: CLIPPER (NCT00962741); CLIPPER2 (NCT01421069).
Asunto(s)
Antirreumáticos , Artritis Juvenil , Artritis Psoriásica , Neoplasias , Niño , Humanos , Adulto Joven , Preescolar , Adolescente , Etanercept/efectos adversos , Artritis Juvenil/tratamiento farmacológico , Antirreumáticos/efectos adversos , Artritis Psoriásica/tratamiento farmacológico , Resultado del Tratamiento , Neoplasias/tratamiento farmacológicoRESUMEN
OBJECTIVE: To report the interim 5-year safety and effectiveness of abatacept in patients with juvenile idiopathic arthritis (JIA) in the PRINTO/PRCSG registry. METHODS: The Abatacept JIA Registry (NCT01357668) is an ongoing observational study of children with JIA receiving abatacept; enrolment started in January 2013. Clinical sites enrolled patients with JIA starting or currently receiving abatacept. Eligible patients were assessed for safety (primary end point) and effectiveness over 10 years. Effectiveness was measured by clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10) in patients with JIA over 5 years. As-observed analysis is presented according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. RESULTS: As of 31 March 2020, 587 patients were enrolled; 569 are included in this analysis (including 134 new users) with 1214.6 patient-years of safety data available. Over 5 years, the incidence rate (IR) per 100 patient-years of follow-up of serious adverse events was 5.52 (95% confidence interval [CI]: 4.27, 7.01) and of events of special interest was 3.62 (95% CI: 2.63, 4.86), with 18 serious infections (IR 1.48 [95% CI: 0.88, 2.34]). As early as month 3, 55.9% of patients achieved cJADAS10 low disease activity and inactive disease (20.3%, 72/354 and 35.6%, 126/354, respectively), sustained over 5 years. Disease activity measures improved over 5 years across JIA categories. CONCLUSION: Abatacept was well tolerated in patients with JIA, with no new safety signals identified and with well-controlled disease activity, including some patients achieving inactive disease or remission. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01357668.
RESUMEN
OBJECTIVE: The aim of this study was to develop and psychometrically validate a self-report instrument to assess (1) competencies, (2) needs, and (3) satisfaction among youth transitioning from pediatric to adult rheumatology. METHODS: The Transition-KompAZ was developed in several steps with conceptual and psychometric analyses. To test its psychometric properties, the instrument was administered to adolescents and young adults (AYAs; 16-25 years) with inflammatory rheumatic diseases before (group 1) or after (group 2) transfer to adult rheumatology. A 2-factor, higher-order confirmatory factor analysis (CFA) model was applied to test the hypothesized factor structure. Internal consistency was estimated using the approach of Raykov with the factor loadings and error variances estimated in the CFA. Spearman rank correlation coefficients were used to assess construct validity. RESULTS: The Transition-KompAZ includes the following modules: (1) competencies in transition (knowledge, self-management), (2) needs (healthcare services, information), and (3) satisfaction (general, transitional care). A total of 173 AYAs (group 1: n = 86; group 2: n = 87) from 12 rheumatology sites completed the Transition-KompAZ. It showed good model fit (comparative fit index > 0.9; Tucker-Lewis index > 0.9; weighted root mean square residual < 0.9) with good internal consistency. The instrument demonstrated moderate-to-good construct validity and good test-retest reliability. CONCLUSION: The Transition-KompAZ appears to be a reliable tool for assessing important dimensions of transition. It may support a structured and individualized transition, as well as the evaluation of transition services. However, further studies are required to assess its predictive value in terms of transfer readiness and successful transition.
RESUMEN
J Rheumatol 2024; doi: 10.3899/jrheum.2024-0097 There were incorrect footnotes in Table 2. All instances of footnote "a" in the Possible Score Range column should be an asterisk. The correct footnote should be, "Only participants with ≤ 1 missing or * additional answer category (ie, "does not currently apply to me") per domain are included for the sum score of the corresponding scale." We apologize for this error. This correction applies only to the August 15 2024 First Release. The correct table appears in the print and online issues.
RESUMEN
The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this consensus provides clinicians with an overview of the diagnosis and treatment of scleromyxoedema and scleroedema (of Buschke).
Asunto(s)
Escleromixedema , Humanos , Escleromixedema/diagnóstico , Escleromixedema/patología , Escleromixedema/terapia , Consenso , Diagnóstico DiferencialRESUMEN
BACKGROUND: Treatment options in patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are currently limited. This trial aimed to demonstrate the efficacy and safety of secukinumab in patients with active ERA and JPsA with inadequate response to conventional therapy. METHODS: In this randomised, double-blind, placebo-controlled, treatment-withdrawal, phase 3 trial, biologic-naïve patients (aged 2 to <18 years) with active disease were treated with open-label subcutaneous secukinumab (75/150 mg in patients <50/≥50 kg) in treatment period (TP) 1 up to week 12, and juvenile idiopathic arthritis (JIA) American College of Rheumatology 30 responders at week 12 were randomised 1:1 to secukinumab or placebo up to 100 weeks. Patients who flared in TP2 immediately entered open-label secukinumab TP3 that lasted up to week 104. Primary endpoint was time to disease flare in TP2. RESULTS: A total of 86 patients (median age, 14 years) entered open-label secukinumab in TP1. In TP2, responders (ERA, 44/52; JPsA, 31/34) received secukinumab or placebo. The study met its primary end point and demonstrated a statistically significant longer time to disease flare in TP2 for ERA and JPsA with secukinumab versus placebo (27% vs 55%, HR, 0.28; 95% CI 0.13 to 0.63; p<0.001). Exposure-adjusted incidence rates (per 100 patient-years (PY), 95% CI) for total patients were 290.7/100 PY (230.2 to 362.3) for adverse events and 8.2/100 PY (4.1 to 14.6) for serious adverse events in the overall JIA population. CONCLUSIONS: Secukinumab demonstrated significantly longer time to disease flare than placebo in children with ERA and JPsA with a consistent safety profile with the adult indications of psoriatic arthritis and axial spondyloarthritis. TRIAL REGISTRATION NUMBER: NCT03031782.
Asunto(s)
Antirreumáticos , Artritis Juvenil , Artritis Psoriásica , Adulto , Niño , Humanos , Adolescente , Artritis Juvenil/tratamiento farmacológico , Antirreumáticos/efectos adversos , Brote de los Síntomas , Resultado del Tratamiento , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/inducido químicamente , Método Doble CiegoRESUMEN
OBJECTIVE: To investigate the impact of additionally given MTX on biologic treatment of polyarticular JIA in terms of effectiveness, safety and drug survival. METHODS: Patients suffering from polyarticular JIA and treated with either monotherapy with a first biologic or a combination of a biologic and MTX were selected from the BIKER registry. The TNF-α inhibitors (TNFi) adalimumab, etanercept and golimumab and the IL-6 inhibitor tocilizumab were considered. Upon a non-randomized study design, we adjusted the different cohorts using propensity score matching to improve comparability. RESULTS: A total of 2148 patients entered the analysis, who were treated by either combination therapy (n = 1464) or monotherapy (n = 684). Disease activity declined significantly more in patients upon combination therapy than upon biologic monotherapy. Comparison of adjusted cohorts revealed that patients who received TNFi gained more benefit from additionally given MTX than patients treated with tocilizumab. Median survival time of therapy with biologics was significantly longer upon combination therapy (3.1 years) than with monotherapy (2.7 years), as demonstrated by a Kaplan-Meier analysis (log rank test: P = 0.002). The safety profile was moderately affected by additional MTX due to increased incidence of gastrointestinal and hepatic adverse events. Serious adverse events occurred at an equal rate of 3.6 events per 100 patient-years in both cohorts. CONCLUSION: Additionally given MTX improves the effectiveness of biologic treatment in polyarticular JIA without seriously compromising treatment safety. Especially TNFi benefit from combination, while no improvement in outcome has been observed by combining tocilizumab with MTX.
Asunto(s)
Antirreumáticos , Artritis Juvenil , Productos Biológicos , Humanos , Metotrexato , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/epidemiología , Antirreumáticos/efectos adversos , Adalimumab/efectos adversos , Etanercept/efectos adversos , Factor de Necrosis Tumoral alfa , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Productos Biológicos/efectos adversos , Resultado del Tratamiento , Quimioterapia CombinadaRESUMEN
OBJECTIVES: To standardly assess and describe nailfold videocapillaroscopy (NVC) assessment in children and adolescents with juvenile rheumatic and musculoskeletal diseases (jRMD) vs healthy controls (HCs). MATERIAL AND METHODS: In consecutive jRMD children and matched HCs from 13 centres worldwide, 16 NVC images per patient were acquired locally and read centrally per international consensus standard evaluation of the EULAR Study Group on Microcirculation in Rheumatic Diseases. A total of 95 patients with JIA, 22 with JDM, 20 with childhood-onset SLE (cSLE), 13 with juvenile SSc (jSSc), 21 with localized scleroderma (lSc), 18 with MCTD and 20 with primary RP (PRP) were included. NVC differences between juvenile subgroups and HCs were calculated through multivariable regression analysis. RESULTS: A total of 6474 images were assessed from 413 subjects (mean age 12.1 years, 70.9% female). The quantitative NVC characteristics were significantly lower or higher in the following subgroups compared with HCs: for density: lower in jSSc, JDM, MCTD, cSLE and lSc; for dilations: higher in jSSc, MCTD and JDM; for abnormal shapes: higher in JDM and MCTD; for haemorrhages: higher in jSSc, MCTD, JDM and cSLE. The qualitative NVC assessment of JIA, lSc and PRP did not differ from HCs, whereas the cSLE and jSSc, MCTD, JDM and cSLE subgroups showed more non-specific and scleroderma patterns, respectively. CONCLUSIONS: This analysis resulted from a pioneering registry of NVC in jRMD. The NVC assessment in jRMD differed significantly from HCs. Future prospective follow-up will further elucidate the role of NVC in jRMD.
Asunto(s)
Enfermedad Mixta del Tejido Conjuntivo , Enfermedades Reumáticas , Esclerodermia Sistémica , Adolescente , Humanos , Niño , Femenino , Masculino , Angioscopía Microscópica/métodos , Uñas/diagnóstico por imagen , Capilares , Enfermedades Reumáticas/diagnóstico por imagen , Esclerodermia Sistémica/diagnóstico por imagenRESUMEN
OBJECTIVE: The aim of our study was to describe the distinct features of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) patients and to identify risk factors for its development. METHODS: Data from the German biologics in pediatric rheumatology registry (Biologika in der Kinderrheumatologie) collected between 2001 and 2021 were analyzed retrospectively. RESULTS: In 5009 JIA patients, 28 developed confirmed IBD before the age of 18 years: 23 (82.1%) with Crohn disease (CD), 4 (14.3%) with ulcerative colitis (UC), and 1 (3.6%) with IBD-unclassified (IBD-U). The incident rate of IBD during 20 years of observation was 0.56% (0.46% for CD, 0.08% for UC, and 0.02% for IBD-U), of whom 20.3% were HLA-B27 positive, 25% had enthesitis-related arthritis, and 14.3% psoriatic arthritis. Within 90 days before IBD diagnosis, 82.1% (n = 23) received treatment with etanercept (ETA), 39.3% (n = 11) non-steroidal anti-inflammatory drugs, 17.9% (n = 5) systemic corticosteroids, 8 (28.6%) methotrexate (MTX), 14.3% (n = 4) sulfasalazine, 10.7% (n = 3) leflunomide, and 3.6% (n = 1) adalimumab and infliximab, respectively. The incidence of IBD was lower in patients treated with MTX, but higher in patients treated with ETA except if ETA was combined with MTX. Also in patients on leflunomide or sulfasalazine, the IBD incidence was higher. CONCLUSIONS: In our JIA cohort, an increased IBD incidence is observed compared to the general population, and the ratio of CD to UC is markedly higher hinting at a distinct phenotype of IBD. Pretreatment with MTX seems to be protective. Treatment with ETA does not prevent IBD development and JIA patients treated with leflunomide and sulfasalazine may be at an increased risk for IBD development.
Asunto(s)
Antirreumáticos , Artritis Juvenil , Productos Biológicos , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Niño , Humanos , Artritis Juvenil/complicaciones , Artritis Juvenil/tratamiento farmacológico , Antirreumáticos/efectos adversos , Productos Biológicos/efectos adversos , Estudios Retrospectivos , Sulfasalazina/efectos adversos , Leflunamida/uso terapéutico , Metotrexato/uso terapéutico , Etanercept/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológicoRESUMEN
BACKGROUND: New therapeutic strategies for juvenile idiopathic arthritis (JIA) have evolved within the past ten years, and as a result, an update of the 2011 recommendations of the German management guidelines was initiated. METHODS: A systemic literature review was performed, overarching principles were proposed and pre-selected via an online survey followed by two multidisciplinary consensus conferences. Pharmacological and non-pharmacological treatments were discussed, statements were proposed and ultimately agreed upon by nominal group technique (NGT). RESULTS: 12 overarching therapeutic principles, as well as 9 recommendations on pharmacological and 5 on non-pharmacological treatments for JIA were agreed upon. CONCLUSION: This report summarizes the recent update of the interdisciplinary, consensus-based German guidelines on the management of JIA. The multi- and interdisciplinary participation of all caregivers was central for this patient-focused update. With these guidelines, physicians can choose an evidence-based approach, which allows better tailored treatment in this vulnerable cohort of children and adolescents.
Asunto(s)
Artritis Juvenil , Adolescente , Niño , Humanos , Artritis Juvenil/tratamiento farmacológico , Consenso , Discapacidades del DesarrolloRESUMEN
OBJECTIVES: To review the effectiveness of secukinumab (SEC) in patients with juvenile idiopathic enthesitis related arthritis (ERA), who had partial or no response on anti-TNF therapy. METHODS: We conducted a retrospective monocentric chart review of patients with ERA, who were treated with SEC, until March 15th 2019. We used the JADAS10 and the Juvenile Spondyloarthritis Disease Activity Index (jspADA) to evaluate response. We analysed the onset of AE and SAE. RESULTS: We analysed 17 patients with ERA. The mean age at the start of the treatment was 19.5 years (SD 4.9, range 13-34 years, median 18.2). The mean disease duration was 6.3 years (SD 3.3, range 2-12 years). The patients received in average 1.9 (SD1.0) different anti-TNF'Ìs before switching to SEC. SEC was applied at the start of the treatment with 150 mg per dose (n=13, 76.5%) and 300 mg per dose (n=4, 23.5%). The dose of 150 mg was increased in 11 patients (85% of 13) after baseline. The mean follow-up of patients was 18.2 months (SD 7.2) accounting to 25.8 years under exposure to SEC. The jspADA (mean change of -1.3; p<0.001; 95%CI: -1.9 to -0.7) and JADAS10 (mean change of -2.4; p=0.021; 95%CI: -4.5 to -0.4) signi cantly improved between baseline and the 24-month follow-up. There was no serious adverse event observed. CONCLUSIONS: In our anti-TNF non-responder patients SEC showed good effectiveness. The 150 mg dose seems to be insufficient in anti-TNF non-responder patients and most patients had to be escalated to the 300 mg/dose.
Asunto(s)
Antirreumáticos , Artritis Juvenil , Espondiloartritis , Adolescente , Adulto , Anticuerpos Monoclonales Humanizados , Antirreumáticos/efectos adversos , Artritis Juvenil/diagnóstico , Artritis Juvenil/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Espondiloartritis/diagnóstico , Espondiloartritis/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Localized scleroderma is an autoimmune disease belonging to the group of collagenoses, which can manifest cutaneously and extracutaneously. The extracutaneous manifestations may have significant morbidity but are not considered in previous scoring systems. For this reason, another scoring system, the total morbidity score (TMS) was developed, which also takes into account the extracutaneous symptoms. METHOD: In the retrospective monocentric study at the Hamburg Center for Pediatric and Adolescent Rheumatology, the TMS was applied to patients from 2004-2019 suffering from localized scleroderma who had at least one control presentation. In addition, data were analyzed according to the previously established localized scleroderma cutaneous assessment tool (LoSCAT) scoring systems to ensure better comparability to the TMS. Furthermore, the score values were considered and compared during the course of treatment with methotrexate (MTX). RESULTS: Due to a lack of control presentations, data from 51 of the 95 patients with a confirmed diagnosis could be included in the retrospective evaluation. The treatment of these patients was considered over a period of 2 years, from the initial presentation over at least 3 further control presentations. The TMS total score remained largely constant. There was a weak correlation between the TMS total score and the localized scleroderma skin damage index (mLoSDI), which indicates the degree of damage. In addition, insignificant changes in the TMS total score were shown over time with MTX treatment (T1/T4: -0.007). DISCUSSION: The evaluation showed that the TMS total score is mainly fed by the extracutaneous manifestations, demonstrating the inaccuracy of previous scores. Another advantage of the TMS is that different scores are assigned depending on whether the feature is new, persistent, improving, or even worsening. The TMS is more time consuming to collect but enables a more accurate assessment of disease activity.
RESUMEN
Juvenile systemic sclerosis (JSSc) is a rare disease of childhood and currently no international consensus exists with regard to its assessment and treatment. This SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) initiative, based on expert opinion informed by the best available evidence, provides recommendations for the assessment and treatment of patients with JSSc with a view to improving their outcome. Experts focused attention not only on the skin assessment but also on the early signs of internal organ involvement whose proper treatment can significantly affect the long-term outcome. A score for disease severity is proposed in order to perform a structured assessment of outcome over time but a validation in a wider patient population is recommended. Finally, a stepwise treatment approach is proposed in order to unify the standard of care throughout Europe with the aim to reduce morbidity and mortality in this disease.
Asunto(s)
Esclerodermia Localizada/tratamiento farmacológico , Esclerodermia Sistémica/tratamiento farmacológico , Niño , Consenso , Medicina Basada en la Evidencia , Humanos , Esclerodermia Localizada/diagnóstico , Esclerodermia Sistémica/diagnóstico , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: To evaluate healthcare services for patients with juvenile idiopathic arthritis (JIA) from the parent-proxy perspective and to identify factors associated with perceived deficits in care. METHODS: Patients with JIA from 11 paediatric rheumatology units were enrolled in an inception cohort within the first 12 months after diagnosis. Healthcare services were assessed using The Child Healthcare Questionnaire on satisfaction, utilisation and needs. Factors associated with deficits in care were identified by logistic regression analysis. RESULTS: Data from parents of 835 JIA-patients were included in the analysis. At the assessment (4.7 months after diagnosis), 85% of the patients received drug treatment, and 50% had received multi-professional care. The most frequently used services were physiotherapy (84%), occupational therapy (23%), and telephone counselling (17%). Almost one-third of families reported that they had not received the services that they needed, with health education being the most frequently reported need. Most parents (93%) were satisfied with the overall healthcare provided for their children, especially regarding doctors' behaviour. However, approximately 1 in 3 consumers were dissatisfied with the time to JIA diagnosis and the school services. The lower the child's quality of life, the higher the chance was that the child and the family received multi-professional care, perceived unmet needs, and were dissatisfied with care. CONCLUSIONS: According to parents' experience and satisfaction with their child's care, performance at the system level can be further improved by diagnosing JIA earlier, providing additional information at disease onset, and ensuring that the child's social environment is taken into account.
Asunto(s)
Artritis Juvenil , Artritis Juvenil/diagnóstico , Artritis Juvenil/epidemiología , Artritis Juvenil/terapia , Niño , Estudios de Cohortes , Atención a la Salud , Humanos , Padres , Calidad de Vida , Encuestas y CuestionariosRESUMEN
To examine whether treatment with interleukin (IL)-1-, IL-6-, tumour necrosis factor α (TNFα)-inhibitors or Abatacept is associated with an increased risk of common infections, infections requiring hospitalization (SAE) or opportunistic infections among real-world juvenile idiopathic arthritis (JIA) patients. Furthermore, the influence of other patient-related covariates on the occurrence of infections was investigated. Patients diagnosed with JIA and treated with biologics were selected from the German BIKER registry. Incidence rates (IR) of infections per 100 person years were calculated and compared between the different cohorts. Using multivariate logistic regression, odds ratios with 95% confidence intervals (CI) were determined for the influence of patient-related covariates (age, diagnosis, laboratory data, concomitant medication, JIA activity, comorbidities, and premedication) on the occurrence of infections. 3258 patients entered the analysis. A total of 3654 treatment episodes were distributed among TNFα- (Etanercept, Adalimumab, Golimumab, Infliximab, n = 3044), IL-1- (Anakinra, Canakinumab, n = 105), IL-6- (Tocilizumab, n = 400) and T-cell activation inhibitors (Abatacept, n = 105). 813 (22.2%) patients had at least one infection, 103 (2.8%) patients suffered from an SAE infection. Both common and SAE infections were significantly more frequent in IL-1 (IR 17.3, 95% CI 12.5/24 and IR 4.3, 95% CI 2.3/8.3) and IL-6 cohort (IR 16.7, 95% CI 13.9/20 and IR 2.8, 95% CI 1.8/4.4) compared to TNFα-inhibitor cohort (IR 8.7, 95% CI 8.1/9.4 and IR 1, 95% CI 0.8/1.3). When comparing the influencing factors for various infectious diseases, the use of corticosteroids, younger age, cardiac comorbidities and higher JIA-activity are the most striking risk factors. Relative to TNFα inhibitors and Abatacept, IL-1 and IL-6 inhibitors were associated with an increased risk of common and SAE infections. The influencing covariates identified may be helpful for the choice of a suitable biologic to treat JIA.
Asunto(s)
Artritis Juvenil/tratamiento farmacológico , Factores Biológicos/efectos adversos , Factores Biológicos/uso terapéutico , Productos Biológicos/uso terapéutico , Factores Inmunológicos/uso terapéutico , Infecciones/epidemiología , Infecciones Oportunistas/epidemiología , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/sangre , Artritis Juvenil/complicaciones , Femenino , Alemania/epidemiología , Humanos , Inmunoglobulina G/efectos adversos , Inmunoglobulina G/uso terapéutico , Incidencia , Interleucina-1/uso terapéutico , Interleucina-6/uso terapéutico , Masculino , Infecciones Oportunistas/inducido químicamente , Sistema de Registros , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: Juvenile idiopathic arthritis is one of the most prevalent chronic inflammatory diseases in children. Evidence suggests that early effective treatment minimises the burden of disease during childhood and in further life. We hypothesise that a guided treat-to-target (T2T) approach is superior to routine care in polyarticular juvenile idiopathic arthritis (pJIA) in terms of reaching a clinical remission after 12 months of treatment. METHODS: Patients with early and active pJIA were enrolled. Targets for treatment were the following: Recognisable Juvenile Arthritis Disease Activity Score (JADAS) improvement after 3 months, acceptable disease at 6 months, minimal disease activity at 9 months and as primary endpoint remission after 12 months. Initially, patients received methotrexate. Failure to meet a defined target required treatment modification at the specified intervals. The choice of biologics was not influenced by the protocol. Finally, T2T patients were compared with a cohort of matched controls of patients with pJIA with unguided therapy documented by BIKER. RESULTS: Sixty-three patients were enrolled. Treatment targets after 3/6/9 and 12 months were reached by 73%/75%/77% and 48% of patients. Fifty-four patients completed the protocol. Compared with matched controls, on T2T guidance significantly more patients reached JADAS remission (48% vs 32%; OR 1.96 (1.1-3.7); p=0.033) and JADAS minimal disease activity (JADAS-MDA) (76% vs 59%; OR 2.2 (1.1-4.4); p=0.028). Patients from the T2T cohort received a biologic significantly more frequent (50% vs 9% after 12 months; OR 9.8 (4.6-20.8); p<0.0001). CONCLUSION: The T2T concept was feasible and superior to unguided treatment. High rates of patients reached JADAS-MDA and JADA remission after 12 months. Approximately half of the patients achieved their therapy goals without a biologic.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Artritis/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Quimioterapia de Inducción/métodos , Adolescente , Artritis/diagnóstico por imagen , Artritis Juvenil/diagnóstico por imagen , Niño , Preescolar , Protocolos Clínicos , Femenino , Humanos , Masculino , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: To evaluate the long-term efficacy and safety of canakinumab to treat patients with colchicine-resistant familial Mediterranean fever (crFMF) during Epoch 4 (weeks 41 to 113) of the CLUSTER study. METHODS: Patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks during a 72-week period. We evaluated disease activity every 8 weeks using the physician global assessment (PGA) of disease activity, counting the number of flares, and measuring concentrations of C reactive protein (CRP) and serum amyloid A (SAA). Safety was studied by determination and classification of observed adverse events (AEs). We analysed safety and efficacy separately in two subgroups of patients receiving a cumulative dose of less than 2700 mg, or equal or more than 2700 mg. RESULTS: Of the 61 patients that started the CLUSTER study, 60 entered Epoch 4 and 57 completed it. During the 72-week period, 35/60 (58.3%) patients experienced no flares, and 23/60 (38.3%) had one flare, as compared with a median of 17.5 flares per year reported at baseline. PGA scores indicated no disease activity for the majority of patients throughout the study. Median CRP concentrations were always lower than 10 mg/L, while median SAA concentrations remained over the limit of normal (10 mg/L) but under the 30 mg/L threshold. No new or unexpected AEs were reported. CONCLUSION: crFMF patients treated with canakinumab during 72 weeks experienced a minimal incidence of flares and good control of clinical disease activity, with no new safety concerns reported.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Fiebre Mediterránea Familiar/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Adolescente , Adulto , Femenino , Humanos , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Using data from the German Biologics JIA Registry (BIKER), long-term safety of biologics for systemic-onset JIA with regard to adverse events of special interest was assessed. METHODS: Safety assessments were based on adverse event reports after first dose through 90 days after last dose. Rates of adverse event, serious adverse event and 25 predefined adverse events of special interest were analysed. Incidence rates were compared for each biologic against all other biologics combined applying a mixed-effect Poisson model. RESULTS: Of 260 systemic-onset JIA patients in this analysis, 151 patients received etanercept, 109 tocilizumab, 71 anakinra and 51 canakinumab. Patients with etanercept had higher clinical Juvenile Arthritis Disease Activity Score 10 scores, active joint counts and steroid use at therapy start. Serious adverse events were reported with higher frequency in patients receiving canakinumab [20/100 patient years (PY)] and tocilizumab (21/100 PY). Cytopenia and hepatic events occurred with a higher frequency with tocilizumab and canakinumab. Medically important infections were seen more often in patients with IL-6 or IL-1 inhibition. Macrophage activation syndrome occurred in all cohorts with a higher frequency in patients with canakinumab (3.2/100 PY) and tocilizumab (2.5/100 PY) vs anakinra (0.83/100 PY) and etanercept (0.5/100 PY). After adjustment only an elevated risk for infections in anakinra-treated patients remained significant. Three definite malignancies were reported in patients ever exposed to biologics. Two deaths occurred in patients treated with etanercept. CONCLUSION: Surveillance of pharmacotherapy as provided by BIKER is an import approach especially for patients on long-term treatment. Overall, tolerance was acceptable. Differences between several biologics were noted and should be considered in daily patient care.
Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Antirreumáticos/efectos adversos , Artritis Juvenil/tratamiento farmacológico , Terapia Biológica/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Preescolar , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Etanercept/efectos adversos , Femenino , Alemania/epidemiología , Humanos , Proteína Antagonista del Receptor de Interleucina 1/efectos adversos , Activación de Macrófagos , Masculino , Vigilancia de Productos Comercializados , Sistema de Registros , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The primary objective was twofold: (1) to determine whether the German version of a screening instrument for clinical practice for juvenile idiopathic arthritis (SICJIA) is reliable in identifying patients at risk for juvenile idiopathic arthritis (JIA), and (2) secondly whether a weighting scheme of individual questions improves its sensitivity. Data were collected and retrospectively analyzed based upon completed SICJIA questionnaires from patients and their guardians at their first clinical visit at the Hamburg Centre for Pediatric and Adolescence Rheumatology. All patients visited the center between August 2015 and July 2017. The survey included 12 disease-orientated questions. For evaluation, only questionnaires of patients diagnosed with JIA or with a non-inflammatory joint pain (NJP) were selected. Standard statistical techniques were used for evaluation. In total, 165 of 800 questionnaires could be used for evaluation. Of the 800 patients who completed questionnaires, 133 were diagnosed with JIA and 32 with NJP. The analysis of the individual questions was performed by comparing the rate of a positive response to the questions between the two groups. Four questions showed a significant difference by comparing the groups, using JIA patients with at least one active joint. The diagnostic accuracy of the weighted sum score increased from 64 to 68% to discriminate between the groups in comparison to the ordinary sum score. An optimal cutoff of 6.0 for referral to a pediatric rheumatologist was calculated. The validation of the SICJIA showed a discriminative difference in patients with clinical diagnosed JIA and a control group diagnosed with NJP. The weighted sum score performed better to differentiate between JIA and NJP patients. The modified SICJIA can be useful to identify patients at risk of JIA.