Jordi Anton

Objective: Macrophage activation syndrome (MAS) is a rare, life‐threatening hyperinflammatory condition that complicates rheumatologic diseases, most commonly Still disease. Despite increasing awareness and emerging recommendations, MAS treatment remains heterogeneous worldwide. The METAPHOR project aimed to describe real‐life therapeutic strategies for MAS, exploring differences across underlying diseases, geographic regions, physician subspecialties, and drug availability. Methods: An international web‐based survey was developed by a multidisciplinary expert panel together with a patient representative following a systematic literature review. The survey was anonymously completed through Paediatric Rheumatology European Society/Paediatric Rheumatology International Trial Organisation and the Histiocyte Society networks (October to December 2023). Treatment strategies for MAS across different rheumatologic contexts were explored. Responses were analyzed descriptively and stratified by geography, subspecialty, clinical experience, and underlying disease. Results: A total of 287 physicians from 64 countries completed the survey, the majority being pediatric rheumatologists with more than five years of experience. Glucocorticoids, particularly intravenous methylprednisolone, were consistently identified as first‐line therapy across all MAS subtypes (for 44% of clinicians as monotherapy). Anakinra, ciclosporin, and intravenous Ig were the most frequently combined agents. However, their use varied markedly by underlying disease and geographic region, with anakinra preferentially used in Still disease–associated MAS. Striking global disparities in drug availability, particularly for anakinra and emapalumab, significantly influenced treatment choices and were associated with increased reliance on steroid monotherapy. Conclusion: MAS management remains highly heterogeneous worldwide. Although glucocorticoids remain foundational, reducing steroid reliance through equitable access to immunomodulatory therapies and advancing mechanism‐based strategies represent critical priorities in optimizing MAS care. image

Objective: Information is limited on the natural history and current treatment patterns in macrophage activation syndrome (MAS), a life‐threatening hyperinflammatory syndrome complicating Still's disease (systemic juvenile idiopathic arthritis [sJIA] and adult‐onset Still's disease [AOSD]). AMETHYST aimed to describe real‐world treatment patterns and outcomes in glucocorticoid (GC)–refractory MAS complicating Still's disease. Methods: In this retrospective cohort study, medical data from January 1, 2012, to March 31, 2023, were abstracted from charts of all eligible patients across eight sites in Europe, Canada, and the United States for index MAS episodes (occurring between January 1, 2012, and September 30, 2022, and meeting eligibility criteria). Results: Overall, 55 of 64 included patients (86%) had sJIA and 9 of 64 (14%) had AOSD. Most patients (53/64 [82.8%]) were children at index (median age: 7.0 years). MAS was characterized by rash (60.4%), fever (52.8%), and hepatic involvement (49.1%). All patients received GCs; most were also treated with anakinra (48/64 [75%]) and/or ciclosporin (33/64 [51.6%]). Normalization of seven (complete MAS laboratory remission) or at least three (partial remission) prespecified laboratory parameters occurred in 7 of 64 (10.9%) and 41 of 64 patients (64.1%), respectively. GCs were tapered in 50 of 64 patients (78.1%) (median: 39.9 days). Per investigator assessment of clinical signs/symptoms for the index MAS episode, 24 of 64 (37.5%) and 26 of 64 patients (40.6%) had a complete and partial response, respectively. MAS recurred in 20 of 64 patients (31.3%). Seven of 64 patients (10.9%) died, and the estimated one‐year survival probability was 93.75%. Conclusions: Low MAS laboratory remission rates and toxicities of high‐dose GCs combined with other treatments highlight the need for safer, more effective therapies.

Objectives Clinical trial data are lacking for treatment of patients with juvenile systemic sclerosis (jSSc). Three published recommendations exist for jSSc but real-world data on treatment patterns are lacking. The aim of this study was to analyse treatments used in the jSSc inception cohort (jSSci) and compare to published recommendations on the treatment of jSSc. Methods Data was extracted for patients with 24 months follow-up visits in the jSSci up until June 2023. Medications used and their association with clinical characteristics were analysed. Logistic regression analyses were performed to compare treatments between limited and diffuse cutaneous jSSc subtypes, organ involvement and time of initiation of treatment. Multilevel mixed effects logistic regression analyses were used to evaluate the change in medication use in follow-up. Treatment patterns were compared against published recommendations. Results 93 patients had 24 months follow-up data. 77% of patients were receiving disease-modifying treatment (DMARD) at enrolment, which increased to 91% at 24 months (pConclusion This is the first report regarding the pattern of medication use in real life in the currently largest patient cohort of patients with jSSc. The observed pattern overlaps with the published recommendations.

Objective: This study aimed to characterize the pharmacokinetics, pharmacodynamics, safety, and exploratory efficacy of subcutaneous belimumab in pediatric patients with active systemic lupus erythematosus (SLE) receiving standard therapy. Methods: This single‐arm, multicenter, open‐label trial (GSK study 200908; ClinicalTrials.gov identifier: NCT04179032) used three‐weight‐band subcutaneous dosing of belimumab 200 mg every week (qw) for pediatric patients weighing ≥50 kg, every 10 days for pediatric patients weighing 30 to <50 kg, and every 2 weeks (q2w) for pediatric patients weighing 15 to <30 kg. The pharmacokinetic profile was characterized by observed concentration at week 12 and population pharmacokinetics (popPK) estimates derived from concentrations over 52 weeks. Pharmacodynamics, safety, and exploratory efficacy (≥4‐point reduction from the baseline Safety of Estrogens in Lupus Erythematosus National Assessment ‐ Systemic Lupus Erythematosus Disease Activity Index [SELENA‐SLEDAI] score) were descriptively evaluated. Alternative two‐weight‐band subcutaneous dosing (≥40 kg: 200 mg qw; 15 to <40 kg: 200 mg q2w) was simulated to predict pharmacokinetics for this regimen. Results: Patients weighing 30 to <50 kg had lower observed belimumab concentrations than those weighing ≥50 kg (week 12 geometric mean 82.8 vs 134 μg/mL), but popPK analyses predicted the three weight bands to be generally consistent and in alignment with established adult subcutaneous and pediatric intravenous exposures. The pharmacodynamic and safety profile was consistent with known belimumab effects. By week 52, 18 of 22 patients (81.8%) had a ≥4‐point reduction from baseline SELENA‐SLEDAI scores. Hypothetical two‐weight‐band dosing simulations predicted consistent exposure across weight bands and in line with established exposures in SLE. Conclusion: Exposure following subcutaneous belimumab administration in pediatric patients is consistent with approved usage; these findings, along with consistent safety and efficacy data, support subcutaneous belimumab use for pediatric patients with SLE. image

Objective: To describe the clinical characteristics, diagnostic findings, treatment, and outcomes of patients with Juvenile Idiopathic Arthritis (JIA) whose initial manifestation was cervical spine arthritis. Methods: This retrospective multicenter study reviewed medical records of JIA patients who presented with cervical spine arthritis as the first and only symptom of the disease. Data collected included clinical presentation, imaging findings at diagnosis and follow-up, age at onset, JIA subtype, disease activity, treatment strategies, and clinical outcomes. Results: Nine patients were identified, five of whom were classified as having oligoarticular-persistent JIA. The mean age at symptom onset was 4.98 ± 3.08 years, with an average diagnostic delay of 6.98 ± 9.78 months. The most common presenting symptom was torticollis (88.9%), followed by limited cervical range of motion (77.8%) and neck pain (55.6%). Cervical MRI was performed in all cases, demonstrating C1–C2 synovitis in every patient and subluxation in four. Initial treatments included nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and methotrexate. Seven patients required escalation to biologic therapy with tumor necrosis factor inhibitors (TNFi), and one underwent surgical arthrodesis. Conclusions: Cervical spine arthritis may be the sole initial manifestation of JIA and should be considered in children with persistent torticollis. Early MRI evaluation is critical for timely diagnosis and monitoring. The frequent need for TNFi therapy highlights the potentially aggressive nature of this presentation and the importance of early recognition and intervention.

Nowadays, digital health technologies, including mobile apps, wearable technologies, social media, websites, electronic medical records, and artificial intelligence, are impacting disease management and outcomes. We aimed to analyse the characteristics and use of digital health tools in juvenile idiopathic arthritis (JIA). We conducted a systematic review (SR) to identify articles examining the characteristics, use, and outcomes (feasibility, usability, and effectiveness) of digital health tools in JIA patients. A sensitive search strategy was performed in Medline, Embase, and Cochrane databases until December 2022 (later updated to March 2024). Two reviewers independently selected the studies and collected the data, including study quality. A descriptive analysis was performed. A total of 21 studies were included, one SR, six randomised controlled trials, four observational studies, four validation studies, one discovery and verification study, and five qualitative studies. Study quality was generally moderate. Most studies focused on patients with JIA (especially young people), but also on parents and health care professionals. Different digital health technologies were investigated, like websites, mobile apps, wearables, and telemedicine. The main objectives of the tools were self-management, symptom and quality of life monitoring, physical activity tracking, disease knowledge improvement, and medication monitoring. Different themes and contents were usually included in the same digital health tool, such as psychological health, lifestyle, intimacy, or shared decision-making. Tool development and validation processes were poorly or not at all described, and data regarding regulatory compliance, security, or privacy were scarce. There is significant variability in the type, characteristics, objectives, and contents of digital health tools for JIA. They still show limitations and gaps, thus highlighting the need for better critical assessment and reporting.

Objective: We aimed to develop consensus‐based recommendations for the monitoring of children with juvenile idiopathic arthritis–associated uveitis (JIAU) in long‐term remission, addressing the absence of international guidance on monitoring schedules for these children and young people.Methods: The Multinational Interdisciplinary Working Group for Uveitis in Childhood convened experts from 10 countries, including pediatric rheumatologists and ophthalmologists, alongside parents of affected children. A review of key longitudinal cohort studies informed a structured consensus process comprising discussion, recommendation development, and voting for adoption, with a consensus threshold of ≥80% needed for adoption. Recommendation development focused on three principal questions: stratification of the risk of poor outcomes, the natural history of JIAU postremission, and the impact of delayed examination.Results: The group established several key recommendations, including a standard monitoring frequency of every 4 months for the first four years following medication cessation, ongoing assessments for patients with structural complications, and low‐frequency monitoring every 6 months for those in stable, drug‐free remission for over four years. There was unanimous agreement on these recommendations.Conclusion: These consensus‐based recommendations provide a framework for monitoring children with JIAU in remission, enhancing the quality of care and optimizing resource use in eye health services. Ongoing research is essential to refine these guidelines as new evidence emerges regarding biomarkers and imaging techniques for disease recurrence.

Kawasaki disease (kDa) has remained a medical mystery for the last five decades with a wide array of hypothesis about potential aetiological factors, that have never been confirmed. In this brief note, I revised the state-of-the-art for the so-called 'wind hypothesis', claiming that the nature and types of aerosols, particularly fine ones, can account for a central part of this research avenue and the relation to kDa. Characterizing their chemical nature, in particular of the composition in trace elements, as well as their biological components (bacteria, fungi and viruses) stands up today as the most promising avenue towards constraining the range of environmental factors modulating or being responsible for this long-debated disease. Understanding kDa thanks to its unprecedented epidemiological record in Japan, going back to before the 1970s, may also improve our understanding of other similar vasculitis and rheumatic diseases.

Background: Rare diseases (RDs) are a heterogeneous group of complex and low-prevalence conditions in which the time to establish a definitive diagnosis is often too long. In addition, for most RDs, few to no treatments are available and it is often difficult to find a specialized care team. Objectives: The project “acERca las enfermedades raras” (in English: “bringing RDs closer”) is an initiative primary designed to generate a consensus by a multidisciplinary group of experts to detect the strengths and weaknesses in the public healthcare system concerning the comprehensive care of persons living with a RD (PLWRD) in the region of Catalonia, Spain, where a Network of Clinical Expert Units (Xarxa d’Unitats de Expertesa Clínica or XUEC) was created and is being implemented since 2015. The additional primary aim was to propose recommendations to solve or improve the limitations found. Methods: A task force of 13 participants with multidisciplinary expertise on RDs completed a questionnaire and participated in two focus groups. A document was drafted with an item series of strengths and weaknesses of the healthcare system regarding the care of PLWRD, and a set of proposals or recommendations to overcome the problems identified. Results: The Catalan Government healthcare model of XUECs for the comprehensive care for RDs is currently valid and adapted to the needs of PLWRD and their families since its strategic optimal and operational framework, and it is aligned with the European Reference Networks (ERNs) thematic areas. The problems found in the current healthcare model were grouped into ten main areas: (1) the healthcare model for RDs; (2) coordination with primary healthcare providers and other tertiary and secondary hospitals; (3) access to and coordination with non-medical services; (4) the role of case manager in the XUEC; (5) genetic diagnosis; (6) undiagnosed patients; (7) treatments; (8) referring process, continuous follow-up, and transition from pediatric to adult centers; (9) research and education for professionals; and (10) associations of PLWRD and their families (patients’ advocacy). The need for more resources was currently detected as the common factor for most of them. Ten key recommendations to improve the healthcare system regarding RDs were postulated. Conclusions: Catalonia has established a unique healthcare model for RDs in Spain, with clear strengths and advantages. However, after analyzing them, the experts suggested that new governmental political and administrative decisions are needed to ensure the efficient implementation of a healthcare plan for PLWRD in Catalonia, which could be applied to other regions and nations worldwide.