Safety and effectiveness of abatacept in juvenile idiopathic arthritis: results from the PRINTO/PRCSG registry.

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.

Recurrent Stroke as a Presenting Feature of Takayasu Arteritis in an Adolescent: A Case Report and Literature Review.

Takayasu arteritis is a large vessel vasculitis, characterized by granulomatous inflammation of arterial vessels, that typically affects the aorta, its main branches and pulmonary arteries. Disease diagnosis is a challenge and requires awareness of the condition, as clinical signs can be not specific. We report a case of an adolescent with recurrent stroke diagnosed with Takayasu arteritis. A diagnosis of Takayasu arteritis was established due to angiographic findings in the magnetic resonance angiography in conjunction with systolic blood pressure discrepancy, arterial hypertension and increased acute phase reactants. Takayasu arteritis is a rare cause of ischemic stroke in children. However, stroke may be the first manifestation of the disease. Clinical experience and multidisciplinary approach, including aggressive treatment, is essential for the favourable outcome of the disease and the reduction of the associated morbidity and mortality.

Effectiveness of the BNT162b2 mRNA COVID-19 vaccine among adolescents with juvenile-onset inflammatory rheumatic diseases.

OBJECTIVES: The effectiveness of the BNT162b2 mRNA COVID-19 vaccine for adolescents with juvenile-onset inflammatory or immune rheumatic diseases (IRDs) is unknown. Several studies have suggested attenuated immunogenicity in patients with IRD. This study evaluated the effectiveness of the BNT162b2 mRNA COVID-19 vaccine in preventing COVID-19 infection in adolescents with juvenile-onset IRD compared with controls without immune rheumatic disease. METHODS: We used data from Clalit Health Services, the largest health-care organization in Israel, to conduct an observational cohort study from February to December 2021, involving 12-18 year-old adolescents diagnosed with IRD. Study outcomes included documented COVID-19 infection in relation to vaccination status and immunomodulatory therapy. We estimated vaccine effectiveness as one minus the risk ratio. Adolescents aged 12-18 years without immune rheumatic disease served as controls. RESULTS: A total of 1639 adolescents with IRD (juvenile idiopathic arthritis, SLE, or familial Mediterranean fever) were included and compared with 524 471 adolescents in the same age range without IRD. There was no difference in COVID-19 infection rates after the second dose of vaccine between those with IRD and controls (2.1% vs 2.1% respectively, P = 0.99). The estimated vaccine effectiveness for adolescents with IRD was 76.3% after the first dose, 94.8% after the second and 99.2% after the third dose. CONCLUSION: We found that the BNT162b2 mRNA vaccine was similarly effective against COVID-19 infection in adolescents with and without IRD. Immunomodulatory therapy did not affect its effectiveness. These results can encourage adolescents with IRD to get vaccinated against COVID-19.

Genetics of longitudinal kidney function in children and adults with systemic lupus erythematosus.

OBJECTIVES: Genome-wide association studies (GWAS) have identified loci associated with estimated glomerular filtration rate (eGFR). Few LN risk loci have been identified to date. We tested the association of SLE and eGFR polygenic risk scores (PRS) with repeated eGFR measures from children and adults with SLE. METHODS: Patients from two tertiary care lupus clinics that met ≥4 ACR and/or SLICC criteria for SLE were genotyped on the Illumina MEGA or Omni1-Quad arrays. PRSs were calculated for SLE and eGFR, using published weighted GWA-significant alleles. eGFR was calculated using the CKD-EPI and Schwartz equations. We tested the effect of eGFR- and SLE-PRSs on eGFR mean and variance, adjusting for age at diagnosis, sex, ancestry, follow-up time, and clinical event flags. RESULTS: We included 1158 SLE patients (37% biopsy-confirmed LN) with 36 733 eGFR measures over a median of 7.6 years (IQR: 3.9-15.3). LN was associated with lower within-person mean eGFR [LN: 93.8 (s.d. 26.4) vs non-LN: 101.6 (s.d. 17.7) mL/min per 1.73 m2; P < 0.0001] and higher variance [LN median: 157.0 (IQR: 89.5, 268.9) vs non-LN median: 84.9 (IQR: 46.9, 138.2) (mL/min per 1.73 m2)2; P < 0.0001]. Increasing SLE-PRSs were associated with lower mean eGFR and greater variance, while increasing eGFR-PRS was associated with increased eGFR mean and variance. CONCLUSION: We observed significant associations between SLE and eGFR PRSs and repeated eGFR measurements, in a large cohort of children and adults with SLE. Longitudinal eGFR may serve as a powerful alternative outcome to LN categories for discovery of LN risk loci.

[Rheumatology centers according to the regulations of the Federal Joint Committee]. / Rheumatologische Zentren entsprechend den Regelungen des Gemeinsamen Bundesausschusses.

With the Nursing Staff Strengthening Act (Pflegepersonal-Stärkungs-Gesetz), the legislator delegated the specification of the special tasks of centers and focal points to the Federal Joint Committee (G-BA). Due to extensive preliminary work it was already possible to agree on quality requirements and special tasks for rheumatology centers and centers for pediatric and adolescent rheumatology in the first version of the G­BA regulations. Since publication in the Federal Gazette (Bundesanzeiger) on 12 March 2020, rheumatology centers have been able to negotiate surcharges for their special tasks if they have been designated accordingly by the state authorities responsible for hospital planning. So far, 14 rheumatological centers have been designated. Many patients continue to be treated in healthcare structures that are not specialized in acute inpatient rheumatological care. In addition to the additional remuneration, the designation as a rheumatology center can also contribute to patients becoming even more aware of the healthcare structures that are specialized for them. Acute inpatient rheumatology has several specializations. Some clinics have specialized in the multimodal treatment of chronic rheumatism patients and have gained a high level of expertise in this field. Many of these highly specialized clinics have so far been denied recognition as a center because the regulations of the G­BA require the provision of further specialist departments at the same location. While for a large number of medical specializations the establishment at a maximum care hospital is likely to make sense, the specialist clinics focusing on the multimodal treatment of chronic rheumatism patients offer the possibility of strengthening rural areas.

Safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine in adolescents with rheumatic diseases treated with immunomodulatory medications.

OBJECTIVES: Adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRDs) could be at risk for disease flare secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or to withholding anti-inflammatory therapy. While vaccination can protect against coronavirus disease 2019 (COVID-19), safety and immunogenicity data regarding anti-SARS-CoV-2 vaccines among adolescents with AIIRDs are limited. This international, prospective, multicentre study evaluated the safety and immunogenicity of the BNT162b2 anti-SARS-CoV-2 vaccine among adolescents and young adults with juvenile-onset AIIRDs, 80% of whom are on chronic immunomodulatory therapy. METHODS: Vaccine side effects, disease activity and short-term efficacy were evaluated after 3 months in 91 patients. Anti-spike S1/S2 IgG antibody levels were evaluated in 37 patients and 22 controls 2-9 weeks after the second dose. RESULTS: A total of 91 patients and 40 healthy controls were included. The safety profile was good, with 96.7% (n = 88) of patients reporting mild or no side effects and no change in disease activity. However, three patients had transient acute symptoms: two following the first vaccination (renal failure and pulmonary haemorrhage) and one following the second dose (mild lupus flare vs viral infection). The seropositivity rate was 97.3% in the AIIRD group compared with 100% among controls. However, anti-S1/S2 antibody titres were significantly lower in the AIIRD group compared with controls [242 (s.d. 136.4) vs 387.8 (57.3) BAU/ml, respectively; P < 0.0001]. No cases of COVID-19 were documented during the 3 month follow-up. CONCLUSION: Vaccination of juvenile-onset AIIRD patients demonstrated good short-term safety and efficacy and a high seropositivity rate but lower anti-S1/S2 antibody titres compared with healthy controls. These results should encourage vaccination of adolescents with juvenile-onset AIIRDs, even while on immunomodulation.

Association of systemic lupus erythematosus (SLE) genetic susceptibility loci with lupus nephritis in childhood-onset and adult-onset SLE.

OBJECTIVE: LN is one of the most common and severe manifestations of SLE. Our aim was to test the association of SLE risk loci with LN risk in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE). METHODS: Two Toronto-based tertiary care SLE cohorts included cSLE (diagnosed <18 years) and aSLE patients (diagnosed ⩾18 years). Patients met ACR and/or SLICC SLE criteria and were genotyped on the Illumina Multi-Ethnic Global Array or Omni1-Quad arrays. We identified those with and without biopsy-confirmed LN. HLA and non-HLA additive SLE risk-weighted genetic risk scores (GRSs) were tested for association with LN risk in logistic models, stratified by cSLE/aSLE and ancestry. Stratified effect estimates were meta-analysed. RESULTS: Of 1237 participants, 572 had cSLE (41% with LN) and 665 had aSLE (30% with LN). Increasing non-HLA GRS was significantly associated with increased LN risk [odds ratio (OR) = 1.26; 95% CI 1.09, 1.46; P = 0.0006], as was increasing HLA GRS in Europeans (OR = 1.55; 95% CI 1.07, 2.25; P = 0.03). There was a trend for stronger associations between both GRSs and LN risk in Europeans with cSLE compared with aSLE. When restricting cases to proliferative LN, the magnitude of these associations increased for both the non-HLA (OR = 1.30; 95% CI 1.10, 1.52; P = 0.002) and HLA GRS (OR = 1.99; 95% CI 1.29, 3.08; P = 0.002). CONCLUSION: We observed an association between known SLE risk loci and LN risk in children and adults with SLE, with the strongest effect observed among Europeans with cSLE. Future studies will include SLE-risk single nucleotide polymorphisms specific to non-European ancestral groups and validate findings in an independent cohort.

Use and perceived relevance of health-related Internet sites and online contact with peers among young people with juvenile idiopathic arthritis.

OBJECTIVE: To evaluate the frequency of use and relevance of health-related Internet (HRI) sites and online peer support groups and their association with demographic, disease-related and psychosocial variables in young people with JIA. METHODS: In a cross-sectional study, 176 young people (10-27 years of age) with JIA were asked to complete a questionnaire. The frequency of using HRI sites (regarding information, medication use and aspects of JIA relating to social life), online peer contact and perceived relevance of HRI sites and online peer communication were determined. Associations with demographic variables, disease activity, medication, emotional behaviour and coping were also examined. RESULTS: Seventy-one per cent of the 142 respondents had used the Internet to search for general information on JIA, but specific topics, such as medication, were searched for less often. Twenty-five per cent of respondents had visited a forum or had contacted peers online. The perceived relevance of HRI sites and online peer contact was rated low (median 2.0 and 1.0, respectively; scale 0-10). Apart from female gender (P < 0.01), none of the demographic and disease-related factors were associated with HRI site use. Coping styles, confrontation and reassuring thoughts were associated with increased HRI site use, but only in males. Internalizing and externalizing problem behaviour were not significantly associated. CONCLUSION: The frequency of HRI site use among young people with JIA was less than expected and was considered of low relevance. HRI sites in their present form cannot replace traditional information as an additional source to increase knowledge.

A comparison of the outcome of adolescent and adult-onset systemic lupus erythematosus.

OBJECTIVE: Previous reports have suggested that juvenile-onset SLE is associated with a worse prognosis than adult-onset disease. There have been limited studies in adolescents. We sought to assess the effect of adolescent-onset SLE on the clinical course of a large multi-ethnic cohort. METHODS: Patients consisted of individuals diagnosed with SLE between 11 and 18 years of age in a tertiary referral centre. All patients with adult-onset disease were used as controls. Data were analysed by univariable and multivariable analysis for demographic, clinical and serological data. RESULTS: One hundred and twenty-four patients with adolescent-onset and 484 patients with adult-onset disease were identified. There was a higher percentage of males (12.9% vs 7.2%; P = 0.036) and patients of Asian ethnicity within the adolescent group (P < 0.01). By univariable analysis, adolescent-onset SLE was associated with more frequent LN and haemolytic anaemia and less serositis and SS. Ischaemic vascular events occurred in 32 adult-onset patients (6.6%) and 3 adolescent-onset patients (2.4%; P = 0.08). Thirty-five adult-onset patients developed cancer (6.8%) compared with five of the adolescent-onset group (4.8%; P = 0.54). The standardized mortality rate was significantly increased in females with adolescent-onset SLE (14.4; 95% CI 4.44, 24.4) compared with patients with adult-onset SLE. By multivariable analysis, adolescent-onset SLE retained a significant association with LN. CONCLUSION: Adolescent-onset SLE is associated with a significantly increased risk of LN and, importantly, with a marked increase in mortality. These data suggest a more aggressive phenotype of disease in patients with onset of SLE in adolescence and supports the need for intensive follow-up and intensive therapy in this population.

Disease activity and prognostic factors in juvenile dermatomyositis: a long-term follow-up study applying the Paediatric Rheumatology International Trials Organization criteria for inactive disease and the myositis disease activity assessment tool.

OBJECTIVES: The aims of this study were to examine disease activity by the Paediatric Rheumatology International Trials Organization (PRINTO) criteria for inactive disease and the Myositis Disease Activity Assessment Tool (MDAAT) in JDM patients after long-term follow-up and to identify predictors of these outcomes. METHODS: A retrospective inception cohort of 59 patients diagnosed with JDM was clinically examined in a cross-sectional study a median of 16.8 years (range 2.0-38.1) after symptom onset. Patients were divided by the PRINTO criteria into clinically inactive and active disease. Disease activity was also measured by MDAAT and other validated tools. Medical records were reviewed for early disease variables and medication. RESULTS: By the PRINTO criteria, 31/59 (51%) patients were active and 29/59 (49%) were inactive. By MDAAT, 43/59 (73%) of the patients had measurable disease activity, most commonly found in the skin (59%) and skeletal (27%) systems. MDAAT showed moderate to strong correlations with other disease activity measures (rsp 0.39-0.87, P < 0.05) except for muscle enzymes. Active patients had higher disease activity than inactive patients measured by MDAAT (P < 0.001) and other disease characteristics (all P ≤ 0.002) except for patients' global assessment of disease activity. After controlling for gender and follow-up time, calcinosis during disease-course predicted high MDAAT, age<9 years at diagnosis predicted active disease and organ damage present 6-12 months post diagnosis predicted both outcomes. CONCLUSION: After 16.8 years, 51-73% of JDM patients had active disease. Disease activity by the PRINTO criteria and MDAAT were moderately to highly associated with most other disease characteristics and was predicted by early damage.

Growing up with chronic pain: a systematic review of the evidence in transitional care for young people with chronic pain.

Objective: Paediatric chronic pain presents a significant individual and societal burden, with an estimated prevalence of 11-38%. A large proportion of adolescents with chronic pain will have unresolved pain that continues into adulthood and thus requires transitional care. The aim of this review was to investigate the current evidence for the core components of effective transitional care interventions designed for young people with chronic pain. Methods: Studies were identified by searching the Embase, MEDLINE, CINAHL and PsycINFO databases. A search strategy using terms such as 'Adolescent', 'Persistent long-term pain' and 'Transition' (or variations of such words) was implemented. Inclusion criteria were sample population age 10-24 years, a confirmed diagnosis of a condition characterized by chronic pain, any healthcare setting, any service provider, published peer reviewed and English language. Results: Ninety-eight articles were identified by the search and 14 were selected after abstract screening. Two independent reviewers screened the articles, followed by a senior reviewer. Of the 14 articles, full-text review found that none of the articles looked specifically at evidence with respect to core components of effective transitional care designed for young people with chronic pain. Conclusion: Chronic pain is a feature of many long-term health conditions. It remains unknown as to whether there are any pain-specific aspects of transitional care. How pain management is addressed in existing transitional care provision and the relationship of pain to outcomes needs further research. If effective interventions can be provided during these crucial years, the trajectory of these young people can potentially be improved into adulthood.

The Role of Age in Delays to Rheumatological Care in Juvenile Idiopathic Arthritis.

OBJECTIVE: To investigate the relationship between age and symptom duration at initial presentation to pediatric rheumatology for juvenile idiopathic arthritis (JIA). METHODS: In children and young people (CYP) enrolled in the Childhood Arthritis Prospective Study prior to March 2018, an association between age at presentation (< 5, 5-11, and > 11 yrs) and symptom duration was tested by multivariable linear regression. RESULTS: In 1577 CYP, 5- to 11-year-olds took 3.2 months longer and > 11-year-olds 6.9 months longer to reach pediatric rheumatology than < 5-year-olds. CONCLUSION: Adolescents take longer to reach pediatric rheumatology, potentially affecting their longer-term outcomes given the window of opportunity for JIA treatment.

Development of a benchmarking toolkit for adolescent and young adult rheumatology services (BeTAR).

BACKGROUND: Young people (YP; 12-24 years old) with rheumatic diseases face many challenges associated with chronic illness in addition to the physiological and psychosocial changes of adolescence. Timely access to developmentally appropriate multidisciplinary care is key to successfully managing rheumatic diseases, but gaps in the care of this vulnerable age group still exist. This study aimed to develop a benchmarking toolkit to enable comparative evaluation of YP rheumatology services in order to promote best practice and reduce variations in service delivery. METHODS: A staged and consultative method was used across a broad group of stakeholders in the UK (YP, parents/other carers, and healthcare professionals, HCPs) to develop this toolkit, with reference to pre-existing standards of YP-friendly healthcare. Eighty-seven YP (median age 19 years, range 12-24 years) and 26 rheumatology HCPs with 1-34 years of experience caring for YP have participated. RESULTS: Thirty quality criteria were identified, which were grouped into four main domains: assessment and treatment, information and involvement, accessibility and environment, and continuity of care. Two toolkit versions, one to be completed by HCPs and one to be completed by patients, were developed. These were further refined by relevant groups and face validity was confirmed. CONCLUSIONS: A toolkit has been developed to systematically evaluate and benchmark YP rheumatology services, which is key in setting standards of care, identifying targets for improvement and facilitating research. Engagement from YP, clinical teams, and commissioners with this tool should facilitate investigation of variability in levels of care and drive quality improvement.

What do young people with rheumatic conditions in the UK think about research involvement? A qualitative study.

BACKGROUND: Involving people of all ages in health research is now widely advocated. To date, no studies have explored whether and how young people with chronic rheumatic conditions want to be involved in influencing health research. This study aimed to explore amongst young people with rheumatic conditions, 1) their experiences of research participation and involvement 2) their beliefs about research involvement and 3) beliefs about how young people's involvement should be organized in the future. METHODS: Focus groups discussions with young people aged 11-24 years with rheumatic conditions across the UK. Data was analysed using a qualitative Framework approach. RESULTS: Thirteen focus groups were held involving 63 participants (45 F: 18 M, mean age 16, range 10 to 24 years) across the UK. All believed that young people had a right to be involved in influencing research and to be consulted by researchers. However, experience of research involvement varied greatly. For many, the current project was the first time they had been involved. Amongst those with experience of research involvement, awareness of what they had been involved in and why was often low. Those who had previously participated in research appeared more positive and confident about influencing research in the future. However, all felt that there were limited opportunities for them to be both research participants and to get involved in research as public contributors. CONCLUSIONS: These findings suggest that there is an on-going need to both increase awareness of research involvement and participation of young people in rheumatology as well as amongst young people themselves.

Transitional care in clinical networks for young people with juvenile idiopathic arthritis: current situation and challenges.

Clinical networks for paediatric and adolescent rheumatology are evolving, and their effect and role in the transition process between paediatric and adult services are unknown. We therefore explored the experiences of those involved to try and understand this further. Health professionals, young people with juvenile idiopathic arthritis and their families were recruited via five national health service paediatric and adolescent rheumatology specialist centres and networks across the UK. Seventy participants took part in focus groups and one-to-one interviews. Data was analysed using coding, memoing and mapping techniques to identify features of transitional services across the sector. Variation and inequities in transitional care exist. Although transition services in networks are evolving, development has lagged behind other areas with network establishment focusing more on access to paediatric rheumatology multidisciplinary teams. Challenges include workforce shortfalls, differences in service priorities, standards and healthcare infrastructures, and managing the legacy of historic encounters. Providing equitable high-quality clinically effective services for transition across the UK has a long way to go. There is a call from within the sector for more protected time, staff and resources to develop transition roles and services, as well as streamlining of local referral pathways between paediatric and adult healthcare services. In addition, there is a need to support professionals in developing their understanding of transitional care in clinical networks, particularly around service design, organisational change and the interpersonal skills required for collaborative working. Key messages • Transitional care in clinical networks requires collaborative working and an effective interface with paediatric and adult rheumatology.• Professional centrism and historic encounters may affect collaborative relationships within clinical networks.• Education programmes need to support the development of interpersonal skills and change management, to facilitate professionals in networks delivering transitional care.