Abstract
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.
Janus kinase (JAK) 1 inhibition represents a precision medicine approach in the treatment of Aicardi–Goutières syndrome (AGS), through targeting of type I interferon‐mediated cell signalling. Blood ...interferon mRNAseq has been proposed as a biomarker of disease with utility in therapeutic monitoring. Objective cerebrospinal fluid (CSF) biomarkers tracking treatment efficacy are currently lacking. Here, we report a retrospective case series of 13 patients (median age 6y, range 2y 6mo–17y; five females, eight males) with AGS demonstrating significantly elevated CSF neopterin levels at first sampling (median 200nmol/L, range 45–2024nmol/L), compared to 13 age‐matched controls with non‐inflammatory neurological conditions (median 23nmol/L, range 5–34nmol/L, p<0.001). Five patients with AGS treated with JAK inhibitors demonstrated a median 81.5% reduction of CSF neopterin (range –36% to –88% change from baseline), compared to eight untreated patients with AGS demonstrating a median 7% reduction in CSF neopterin (range –63% to +117% change) (p=0.047). Our data indicate a biological effect of JAK inhibitors, and the potential role of CSF neopterin as a biomarker of treatment response.
Objective
To evaluate changes in health‐related quality of life (HRQoL) and disability in children with systemic juvenile idiopathic arthritis (JIA) or polyarticular JIA treated with tocilizumab.
...Methods
Secondary analyses of two double‐blind, placebo‐controlled trials of intravenous tocilizumab in children with active systemic JIA or polyarticular JIA were conducted. Patient‐reported outcomes of disability (Childhood Health Assessment Questionnaire C‐HAQ), HRQoL (Child Health Questionnaire Parent Form 50 CHQ‐P50, health concepts, physical summary score CHQ‐P50‐PhS, psychosocial summary score CHQ‐P50‐PsS), pain, and well‐being (100‐mm visual analog scale VAS) were measured at weeks 0 and 12 for systemic JIA, weeks 16 and 40 for polyarticular JIA, and week 104 for both JIA subgroups.
Results
The trial included 112 patients with systemic JIA and 188 patients with polyarticular JIA. In patients with polyarticular JIA, the mean ± SD C‐HAQ score decreased from 1.39 ± 0.74 at baseline to 0.67 ± 0.65 at week 16 (P < 0.001). In patients with systemic JIA, the mean ± SD CHQ‐P50‐PhS improved more with tocilizumab therapy than with placebo at week 12 (7.3 ± 10.2 versus 2.4 ± 10.6) (P < 0.05). Almost all mean CHQ‐P50 health concept scores, CHQ‐P50‐PsS, and CHQ‐P50‐PhS improved (P ≤ 0.002) by week 104 for patients with systemic JIA. Patients with polyarticular JIA and patients with systemic JIA showed significant reductions in disability (mean ± SD C‐HAQ scores of −1.09 ± 0.71 and −1.17 ± 0.80, respectively), improvements in well‐being (mean ± SD well‐being VAS scores of −43.76 ± 26.61 and −51.53 ± 23.57, respectively), and decreases in pain (mean ± SD pain VAS scores of −41.56 ± 31.06 and −51.26 ± 26.79, respectively) (P < 0.001); in patients with polyarticular JIA and patients with systemic JIA who were treated with tocilizumab, 92.9% of polyarticular JIA patients and 96.8% of systemic JIA patients reported no more than minimal pain (a score of ≤35 mm on the VAS) at week 104.
Conclusion
Tocilizumab treatment was associated with significantly reduced disability and pain and improved HRQoL in patients with systemic JIA and polyarticular JIA.
Objective
Disease activity, organ damage, and treatment burden are often substantial in children and adolescents with systemic lupus erythematous (SLE), and the complex interplay among the developing ...child, parents, and peers makes effective management difficult. We aimed to describe the experiences and perspectives of adolescents and young adults diagnosed with juvenile‐onset SLE to inform strategies for improving treatment and health outcomes.
Methods
Focus groups and face‐to‐face semistructured interviews were conducted with 26 patients ages 14–26 years, from 5 Australian hospitals in 2013–2014. Focus groups and interview transcripts were thematically analyzed.
Results
Five themes were identified: marring identity (misrepresented self, heightened self‐consciousness, sense of isolation), restricting major life decisions (narrowed career options, threat to parenthood), multifaceted confusion and uncertainty (frustration at delayed diagnosis or misdiagnosis, needing age and culturally appropriate information, ambiguity about cause of symptoms, prognostic uncertainty, confronting transition to adult care), resentment of long‐term treatment (restricting ambition, animosity toward medication use), and gaining resilience and coping capacities (desire for independence, developing self‐reliance, recalibrating perceived disease severity, depending on family and friends, trusting physicians).
Conclusion
Young patients with SLE perceive they have substantially limited physical and social capacities and restricted personal and career goals. Psychosocial and educational interventions targeted at improving confidence, self‐efficacy, disease‐related knowledge, and social support, and at resolving insecurities regarding patients’ capacity for self‐management may alleviate psychosocial distress and improve adherence, and thus optimize health outcomes of adolescents and young adults with SLE.
The main objective was to determine the 2-year clinical benefit and safety of etanercept (ETN) in children with the juvenile idiopathic arthritis (JIA) categories of extended oligoarthritis (eoJIA), ...enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA).
CLIPPER was a 96-week, phase IIIb, open-label, multicenter study. Patients with eoJIA, ERA, or PsA received ETN 0.8 mg/kg once weekly (50 mg max) for up to 96 weeks. The proportions of patients reaching the JIA American College of Rheumatology (ACR) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated. Adverse events (AE) were collected throughout the study (intention-to-treat sample).
There were 127 patients (eoJIA n = 60, ERA n = 38, PsA n = 29) who received ≥ 1 dose of ETN. The mean disease duration was 31.6 (eoJIA), 23.0 (ERA), and 21.8 (PsA) months. At Week 96, JIA ACR 30/50/70/90/100/inactive disease responses (95% CI) were achieved by 84.3% (76.7, 90.1), 83.5% (75.8, 89.5), 78.7% (70.6, 85.5), 55.1% (46.0, 63.9), 45.7% (36.8, 54.7), and 27.6% (20.0, 36.2) of patients, respectively. The most common AE (no. events, events per 100 patient-yrs) overall were headache (23, 10.7), pyrexia (12, 5.6), and diarrhea (10, 4.6). The most common infections were upper respiratory tract infection (83, 38.6), pharyngitis (50, 23.2), gastroenteritis (22, 10.2), bronchitis (19, 8.8), and rhinitis (17, 7.9). No cases of malignancy, active tuberculosis, demyelinating disorders, or death were reported.
Over 96 weeks of therapy, ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories, with no major safety issues.
Importance
Paediatric uveitis is a severe sight‐threatening uveitis due to disease progression and treatment failure. Biological agents are a promising new treatment. This study provides real‐world ...data on their use from Sydney, Australia.
Background
Traditionally corticosteroids and non‐biological immunosuppressive agents were used to treat paediatric uveitis, often with poor outcomes.
Design
Retrospective, chart review over an 8‐year period at a tertiary referral eye hospital.
Participants
A total of 27 paediatric uveitis patients treated with biological agents.
Methods
Chart review of demographic data and treatment outcomes.
Main Outcome Measures
Treatment efficacy (corticosteroid‐sparing effect, topical steroid cessation/reduction, reduction in systemic‐steroid sparing agents, change in intraocular inflammation, visual acuity and central macular thickness); treatment failure; and adverse events. Data were collected at biological initiation, 6 weeks, 6 months and 12 months.
Results
Biological therapy over 1 year was effective with prednisolone dose reduced to <5 mg/day in five of six patients (83%), number of systemic steroid‐sparing agents was reduced to ≤1 in two of four patients (50%) and cessation of topical steroid achieved in 12/41 of eyes (29%). Improvement of anterior chamber cells by two grades occurred in 20/25 eyes (80%), improvement of logMAR to ≤0.3 occurred in 12/18 eyes (67%) and macular oedema decreased in 4/5 eyes (80%). Treatment failure occurred in six eyes (13.01%) and five patients (18.5%) developed an adverse reaction.
Conclusions and Relevance
Biological therapy was effective in paediatric patients with uveitis. Intraocular inflammation improved with maintained visual acuity, systemic corticosteroid dose decreased and there was a low frequency of adverse events.
Background/Purpose:
The phase 3 CHERISH trial demonstrated the efficacy of tocilizumab (TCZ), an interleukin‐6 receptor inhibitor, in patients with polyarticular‐course juvenile idiopathic arthritis ...(pcJIA). This analysis investigated the progression of radiographic joint damage in patients with pcJIA treated with TCZ for up to 104 weeks in CHERISH.
Methods:
Patients 2 to 17 years old with ≥6 months' active pcJIA for whom methotrexate failed received open‐label (OL) TCZ according to body weight (BW) (BW ≥30 kg, 8 mg/kg n = 119; BW <30 kg, randomly assigned 1:1 to 8 mg/kg n = 34 or 10 mg/kg n = 35) every 4 weeks for 16 weeks. At 16 weeks, eligible patients (≥JIA ACR30 response) entered a 24‐week, randomized, double‐blind withdrawal period and were assigned 1:1 to placebo or continued TCZ. All patients entered an OL extension through week 104. Those receiving TCZ in all 3 parts were included in the continuous TCZ subgroup for which key radiographic end points were assessed. Radiographic progression was indicated as a positive change in adapted Sharp/van der Heijde score () (aSH) and/or a negative change in Poznanski score (), assessed on hand and wrist radiographs, from baseline to weeks 52 and 104.
Results:
Baseline and ≥1 postbaseline aSH and Poznanski scores were available for 45 and 35 patients, respectively, in the continuous TCZ subgroup and for 87 and 61 patients, respectively, in the total population. Reasons for missing data included early withdrawal, no consent, or unreadable radiographs (because of advanced damage resulting in unreliable measurements or growth plate fusion in postpubertal children), preventing assessment of Poznanski scores. Baseline demographics and disease characteristics were balanced for aSH and Poznanski populations and were similar to those for the full study population. At weeks 52 and 104, median changes from baseline aSH score of 0.5 (p = 0.70) and −1.0 (p = 0.11), respectively, and median changes from baseline Poznanski score of 0.3 (p = 0.07) and 0.6 (p = 0.004), respectively, indicating a lack of radiographic progression. With a cutoff of the smallest detectable difference, no radiographic progression was seen in 87.5% and 97.1% of patients based on aSH scoring and 93.5% and 96.0% of patients based on Poznanski scoring at weeks 52 and 104, respectively. Comparable proportions of the total radiographic population, including those exposed to placebo, remained radiographic progression free at week 104. Among the radiographic population, the annualized rates of progression to week 104 for aSH and Poznanski scores were 0.00 and 0.18, respectively.
Conclusion:
TCZ halted the progression of radiographic damage, leaving a large majority of pcJIA patients free of radiographic progression after 2 years of treatment.
Aging impairs the control of many skilled movements including speech. The purpose of this paper was to investigate whether young and older adults adapt to lower lip perturbations during speech ...differently. Twenty men (10 young, 26 ± 3 years of age; 10 older, 60 ± 9 years of age) were requested to repeat the word (“papa”) 300 times. In 15% of the trials, the subjects experienced a mechanical perturbation on the lower lip. Displacement and neural activation (EMG) of the upper and lower lips were evaluated. Perturbations to the lower lip caused a greater increase in the maximum displacement of the lower lip for older adults compared with young adults (34.7 ± 19% vs. 13.4 ± 17%; P = 0.017). Furthermore, young adults exhibited significantly greater 30-100 Hz normalized EMG power for the lower lip compared to the upper lip (P < 0.005). In young adults, changes from normal to perturbed trials in the 30-50 Hz frequency band of the EMG were negatively correlated to the changes from normal to perturbed trials in the lower lip maximum displacement (R ² = 0.48; P = 0.025). It is concluded that young adults adapt better to lower lip perturbations compared with older adults and that the associated neural activation strategy of the involved muscle is different for the two age groups.
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