Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force.

OBJECTIVE: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. METHODS: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. RESULTS: The Task Force proposed two definitions of remission: 'cSLE clinical remission on steroids (cCR)' and 'cSLE clinical remission off steroids (cCR-0)'. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0-3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. CONCLUSIONS: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

Priorities in Chronic nonbacterial osteomyelitis (CNO) - results from an international survey and roundtable discussions.

OBJECTIVE: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder that predominantly affects children and young people. The pathophysiology and molecular mechanisms of CNO remain poorly understood, and diagnostic criteria and biomarkers are lacking. As a result, treatment is empiric and follows personal experience, case series and expert consensus plans. METHODS: A survey was designed to gain insight on clinician and patient experiences of diagnosing and treating CNO and to collate opinions on research priorities. A version containing 24 questions was circulated among international expert clinicians and clinical academics (27 contacted, 21 responses). An equivalent questionnaire containing 20 questions was shared to explore the experience and priorities of CNO patients and family members (93 responses). RESULTS: Responses were used to select topics for four moderated roundtable discussions at the "International Conference on CNO and autoinflammatory bone disease" (Liverpool, United Kingdom, May 25-26th, 2022). The group identified deciphering the pathophysiology of CNO to be the highest priority, followed by clinical trials, necessary outcome measures and classification criteria. Surprisingly, mental wellbeing scored behind these items. CONCLUSIONS: Agreement exists among clinicians, academics, patients and families that deciphering the pathophysiology of CNO is of highest priority to inform clinical trials that will allow for the approval of medications for the treatment of CNO by regulatory agencies.

Gathering expert consensus to inform a proposed trial in chronic nonbacterial osteomyelitis (CNO).

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and adolescents. CNO is associated with pain, bone swelling, deformity, and fractures. Its pathophysiology is characterized by increased inflammasome assembly and imbalanced expression of cytokines. Treatment is currently based on personal experience, case series and resulting expert recommendations. Randomized controlled trials (RCTs) have not been initiated because of the rarity of CNO, expired patent protection of some medications, and the absence of agreed outcome measures. An international group of fourteen CNO experts and two patient/parent representatives was assembled to generate consensus to inform and conduct future RCTs. The exercise delivered consensus inclusion and exclusion criteria, patent protected (excludes TNF inhibitors) treatments of immediate interest (biological DMARDs targeting IL-1 and IL-17), primary (improvement of pain; physician global assessment) and secondary endpoints (improved MRI; improved PedCNO score which includes physician and patient global scores) for future RCTs in CNO.

PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS).

OBJECTIVE: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. METHODS: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. RESULTS: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. CONCLUSIONS: A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.

The importance of children and young person involvement in scoping the need for a paediatric glucocorticoid-associated patient reported outcome measure.

BACKGROUND: For many children and young people (CYP) with paediatric rheumatic conditions, glucocorticoid medications and their associated side-effects have a substantial impact on disease experience. Whilst there are physician-rated measures of glucocorticoid toxicity, no parallel patient reported measure has been developed to date for CYP with rheumatic disease. This manuscript describes a series of public patient involvement (PPI) events to inform the development of a future paediatric glucocorticoid-associated patient reported outcome measure (PROM). METHODS: One large group PPI event was advertised to CYP with experience of glucocorticoid medication use and their parents through clinicians, charities and existing PPI groups. This featured education on the team's research into glucocorticoid medication and interactive polls/structured discussion to help participants share their experiences. Further engagement was sought for PPI group work to co-develop future glucocorticoid studies, including development of a glucocorticoid associated PROM. Quantitative and qualitative feedback was collected from online questionnaires. The initiative was held virtually due to the Covid-19 pandemic. RESULTS: Nine families (n = 15) including 6 CYP joined the large group PPI event. Online pre-attendance and post-attendance questionnaires showed improvement in mean self-reported confidence [1 = not at all confident, 5 = very confident] in the following: what steroid medications are (pre = 3.9, post = 4.8), steroid side effects (pre = 3.8, post = 4.6), patient-reported outcome measures (pre = 2.0, post = 4.5), available research on steroids (pre = 2.2, post = 3.5). Five families (n = 7) were involved in a monthly PPI group who worked alongside the research team to identify priorities in glucocorticoid research, produce age-appropriate study materials, identify barriers to study participation (e.g. accessibility & convenience) and recommend appropriate modalities for dissemination. The participants found discussing shared experiences and learning about research to be the most enjoyable aspects of the initiative. CONCLUSIONS: This PPI initiative provided a valuable forum for families, including young children, to share their perspectives. Here, the authors explore the effective use of PPI in a virtual setting and provide a unique case study for the involvement of CYP in PROM development. The monthly PPI group also identified a need for the development of a new PROM related to glucocorticoid medication use and provided unique insights into how such a study could be structured.

Monogenic mimics of Behçet's disease in the young.

OBJECTIVES: Monogenic autoinflammatory disorders (AID) and primary immunodeficiencies can present early in life with features that may be mistaken for Behçet's disease (BD). We aimed to retrospectively describe the clinical and laboratory features of 11 paediatric cases referred for suspected BD who turned out to have an alternative, monogenic disease mimicking BD. METHODS: Retrospective, paediatric BD specialist multicentre case series. Next generation sequencing (NGS) or conventional candidate gene screening approaches were utilized, facilitated in some cases by functional assays. RESULTS: Eleven children referred with suspected BD underwent genetic screening because of atypical BD features, and/or presentation before age 5 years. Eight patients (73%) were Caucasian, two were Pakistani and one was Turkish; 55% were female. A positive family history of BD was reported in 54% cases. The median age of disease onset was 0.6 (range 0.2-2.3) years. All had systemic inflammation and oral ulceration; 5/11 had genital ulceration; 3/11 had ocular involvement; and 9/11 had cutaneous manifestations. Nine/11 had known disease-causing genetic mutations in: TNFAIP3 (n = 2), WDR1 (n = 2), NCF1, AP1S3, LYN, MEFV and GLA. The remaining two cases each had novel variants in STAT1 and TNFRSF1A. CONCLUSION: Rare monogenic diseases can mimic BD, particularly when presenting early in life. These observations are now informing a strategy to explore screening for genetic mimics of BD in a UK cohort of children and adults to better understand the proportion of UK BD patients who may in fact have an underlying monogenetic diagnosis.