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Objectives To elicit and quantify expert opinion concerning the relative merits of two treatments for a rare inflammatory disease: JDM. The formal expression of expert opinion reported in this article will be used in a Bayesian analysis of a forthcoming randomized controlled trial known as BARJDM (baricitinib for JDM). Methods A Bayesian prior elicitation meeting was convened, following a previously described methodological template. Opinion was sought on the probability that a patient in the BARJDM trial would achieve clinically inactive disease, off glucocorticoids (GC) within a 12-month period with either MTX (standard of care); or baricitinib (a Janus kinase inhibitor, JAKi), with GC schedules identical in both arms of the trial. Experts' views were discussed and refined following presentation and further discussion of summated published data regarding efficacy of MTX or JAKi for JDM. Results Ten UK paediatric rheumatology consultants (including one adolescent paediatric rheumatologist) participated in the elicitation meeting. All had expertise in JDM, leading active National Health Service clinics for this disease. Consensus expert prior opinion was that the most likely probability of clinically inactive disease off GC within 12 months was 0.55 on baricitinib and 0.23 on MTX, with a greater degree of uncertainty for baricitinib. Conclusion Experts currently think that baricitinib is superior to MTX for the treatment of JDM, although there is uncertainty around this. BARJDM will therefore integrate randomized trial data with this expert prior opinion to derive a posterior distribution for the relative efficacy of baricitinib compared with MTX. [ABSTRACT FROM AUTHOR]

Objectives SS with childhood onset is a rare autoimmune disease characterized by heterogeneous presentation. The lack of validated classification criteria makes it challenging to diagnose. Evidence-based guidelines for treatment of juvenile SS are not available due to the rarity of disease and the paucity of research in this patient population. This systematic review aims to summarize and appraise the current literature focused on pharmacological strategies for management of SS with childhood onset. Methods PubMed and MEDLINE/Scopus databases up to December 2020 were screened for suitable reports highlighting pharmacological treatment of SS with childhood onset using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 reporting checklist. Animal studies were excluded. Results A total of 43 studies (34 case reports, 8 mini case series and 1 pilot study) were eligible for analysis. The studies retrieved included girls in 88% (120/137) of cases and had very low confidence levels. HCQ was prescribed for parotid swelling, as well as in association with MTX and NSAIDs in patients with arthritis and arthralgia. Corticosteroids such as long courses of oral prednisone and i.v. methylprednisolone were commonly prescribed for children with severe disease presentations. Rituximab was mainly indicated for mucosa-associated lymphoid tissue lymphoma and renal and nervous system complications. Other conventional DMARDs were prescribed in selected cases with extraglandular manifestations. Conclusion Various therapies are used for the management of juvenile SS and are prescribed based on expert clinician's opinion. There are currently no good-quality studies that allow clinical recommendations for treatment of SS with childhood onset. [ABSTRACT FROM AUTHOR]

Poster presentation Tuesday 8 October Background Antinuclear antibodies (ANA) are autoantibodies that recognise cellular antigens found predominantly in the cell nucleus. They are associated with numerous autoimmune diseases such as systemic lupus erythematosus, but may also be found in infectious diseases, malignancies and healthy individuals. ANA is requested as part of an initial work-up for autoimmune conditions. In healthy children (5-18%), positive ANA titres of 1/80 to 1/320 have been reported. A prospective study of healthy children with positive ANA found that children who developed autoimmune disease had clinical features at presentation that were suspicious for such an outcome. Therefore, the usefulness of a positive ANA result for diagnosing autoimmune conditions is limited without clinical correlation. The aim of our study was to assess whether high ANA titre and clinical features at presentation could predict final diagnosis. Methods Single centre retrospective study at Great Ormond Street Hospital for Children (GOSH). The immunology laboratory provided a list of positive ANA results (using indirect immunofluorescence technique) from January 2013 to July 2018. A retrospective chart review was performed to ascertain presence of clinical features at presentation under the five following titles: arthritis, skin involvement, eyes, CNS involvement and Raynaud's phenomenon. We then reviewed the last clinical contact to document confirmed diagnosis. Results We performed a retrospective chart review on 1,354 children (67% female; median age 7.5 years (0.1-17.5); median follow-up 4.8 years (0-18)) with positive ANA results (titres 1/160, 1/320, 1/640, 1/1280, 1/2560 and >1/2560). Table 1 reports ANA titres at first presentation in relation to final diagnosis. A titre of 1/640 or above was most commonly seen (>50%) in children with an autoimmune rheumatology condition. In fact, children with the highest titre (>1:2560) were significantly more likely to be diagnosed with one of these conditions. Finally, we looked at the number of presenting features and correlated with final diagnosis. Those diagnosed with a CTD were most likely to present with 2-5 clinical features (p < 0.0001). P24 Table 1: Percentage of patients grouped according to their diagnosis and ANA titres Final Diagnoses   ANA Titres   >1: 2560   1: 2560   1: 1280   1: 640   1: 320   1: 160     Connective Tissue Diseases  24%  9%  13%  16%  16%  22%  JIA and Uveitis  8%  11%  15%  22%  22%  22%  JIA  6%  8%  13%  24%  24%  25%  Autoimmune (other)  4%  5%  11%  19%  32%  29%  Unidentified autoimmune/ autoinflammatory  8%  12%  -  24%  12%  44%  Vasculitis  -  -  5%  26%  16%  53%  Sarcoidosis  -  20%  -  20%  -  60%  Autoinflammatory  7%  -  -  43%  -  50%  Malignancy  -  -  -  25%  -  75%  Other  3%  2%  3%  17%  28%  47%  Non-inflammatory MSK  3%  -  9%  18%  27%  43%  Final Diagnoses   ANA Titres   >1: 2560   1: 2560   1: 1280   1: 640   1: 320   1: 160     Connective Tissue Diseases  24%  9%  13%  16%  16%  22%  JIA and Uveitis  8%  11%  15%  22%  22%  22%  JIA  6%  8%  13%  24%  24%  25%  Autoimmune (other)  4%  5%  11%  19%  32%  29%  Unidentified autoimmune/ autoinflammatory  8%  12%  -  24%  12%  44%  Vasculitis  -  -  5%  26%  16%  53%  Sarcoidosis  -  20%  -  20%  -  60%  Autoinflammatory  7%  -  -  43%  -  50%  Malignancy  -  -  -  25%  -  75%  Other  3%  2%  3%  17%  28%  47%  Non-inflammatory MSK  3%  -  9%  18%  27%  43%  P24 Table 1: Percentage of patients grouped according to their diagnosis and ANA titres Final Diagnoses   ANA Titres   >1: 2560   1: 2560   1: 1280   1: 640   1: 320   1: 160     Connective Tissue Diseases  24%  9%  13%  16%  16%  22%  JIA and Uveitis  8%  11%  15%  22%  22%  22%  JIA  6%  8%  13%  24%  24%  25%  Autoimmune (other)  4%  5%  11%  19%  32%  29%  Unidentified autoimmune/ autoinflammatory  8%  12%  -  24%  12%  44%  Vasculitis  -  -  5%  26%  16%  53%  Sarcoidosis  -  20%  -  20%  -  60%  Autoinflammatory  7%  -  -  43%  -  50%  Malignancy  -  -  -  25%  -  75%  Other  3%  2%  3%  17%  28%  47%  Non-inflammatory MSK  3%  -  9%  18%  27%  43%  Final Diagnoses   ANA Titres   >1: 2560   1: 2560   1: 1280   1: 640   1: 320   1: 160     Connective Tissue Diseases  24%  9%  13%  16%  16%  22%  JIA and Uveitis  8%  11%  15%  22%  22%  22%  JIA  6%  8%  13%  24%  24%  25%  Autoimmune (other)  4%  5%  11%  19%  32%  29%  Unidentified autoimmune/ autoinflammatory  8%  12%  -  24%  12%  44%  Vasculitis  -  -  5%  26%  16%  53%  Sarcoidosis  -  20%  -  20%  -  60%  Autoinflammatory  7%  -  -  43%  -  50%  Malignancy  -  -  -  25%  -  75%  Other  3%  2%  3%  17%  28%  47%  Non-inflammatory MSK  3%  -  9%  18%  27%  43%  Conclusion This study suggests that, patients presenting with higher ANA titres and a combination of clinical features should be assessed systemically and followed-up as they may have increased risk of developing an autoimmune rheumatological conditions. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Tocilizumab, approved for treatment of children >2years with SoJIA and polyarticular JIA (pJIA) is efficacious and well-tolerated. Transient neutropenia as a side-effect of treatment has been reported. Our aim was to perform a retrospective chart review of children treated with Tocilizumab and report our experience of tocilizumab-associated neutopenic episodes. Methods Retrospective review of patients receiving tocilizumab (January 2010-January 2019) performed and baseline demographics recorded. Patients with a diagnosis of extended-oligoarticular JIA (ExO-JIA), pJIA and SoJIA were reviewed in more detail to ascertain frequency of neutropenia and related-factors. For the purpose of analysis, ExO-JIA and pJIA were combined to create an ExO/pJIA group. Neutropenia was defined as neutrophils<1.5 and severe neutropenia as < 1.0. Statistical analysis was performed using the Mann-Whitney-U and Chi-Square tests. Results Sixty-eight children (60% female) attending the rheumatology department at GOSH are receiving tocilizumab. Of these, 53 (78%) have a diagnosis of ExO-JIA (n = 10), pJIA (n = 12) or SoJIA (n = 31). Median age at diagnosis was 4.4years (0.2–14.7). Disease duration pre-commencement of tocilizumab was 2.9years (0.1–11). Children with SoJIA were commenced on tocilizumab significantly (p < 0.001) earlier in their disease course than children with ExO/pJIA (1.5 years, 0.1–7.4 versus 6.5 years, 0.4-11 respectively). However, there was no significant difference in number of alternative treatments received pre-tocilizumab between groups. Concurrent methotrexate administration was similar between groups. In contrast, concurrent use of steroids in SoJIA (27/31, 87%) was significantly more frequent (p < 0.00001) than in ExO/pJIA (2/22, 9%). All children commenced on tocilizumab had a normal preceding white cell and neutrophil count. Median time to first episode of neutropenia was 0.5years (0.1-3.2). No significant pattern in time from commencing tocilizumab to developing first episode of neutropenia was observed (40% developed neutropenia after >6months on tocilizumab). Recurrent neutropenia (i.e. >2 episodes of neutropenia) was observed in 38% (20/53) and was significantly more common in children with SoJIA compared to ExO/pJIA (p < 0.05). All children with ExO/pJIA experienced a total of 2-3 neutropenic episodes, significantly less (p < 0.05) than the recurrence rate in children with SoJIA (median 7 episodes, 2-17). Severe neutropenia was observed in 65% (n = 13), occurring significantly (p < 0.001) more frequently in SoJIA (n = 11, 85%) than ExO/pJIA. In those with recurrent neutropenia, no significant correlation was identified between risk of neutropenia and interval between doses, dose (mg/kg) received, concurrent administration of methotrexate, duration on tocilizumab or number of alternative treatments received pre-tocilizumab. Finally, 17 children (32%) taking tocilizumab had a documented infection, but no relationship between neutropenia and risk of infection was identified. Conclusion Tocilizumab-associated neutropenia is more frequently observed, more severe and more often recurrent in children with SoJIA. Neutropenia can occur at any stage in the treatment course, therefore clinicians should consider continuing blood-monitoring pre-tocilizumab long-term, with particular attention paid to those diagnosed with SoJIA. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Poster presentation Tuesday 8 October Background Sjögren's syndrome, a chronic multisystem autoimmune disease is characterised by inflammation of the exocrine glands, principally the salivary and lacrimal glands resulting in xerostomia and xerophthalmia. It can also present with more extensive exocrinopathy as well as extra-glandular, systemic features. Defined as primary SS (pSS) when there is no association with other autoimmune disease, reported incidence and prevalence rates vary. Juvenile-onset pSS is believed to be rare; however it is likely that it is under-recognised and therefore under-diagnosed. To date there have been no studies reporting accurate incidence or prevalence of paediatric pSS (PpSS). Diagnosing pSS can be challenging. Many of the cardinal symptoms are non-specific and no gold standard biomarker of disease exists. Between 1965–2002 eleven diagnostic criteria sets were developed, none of which have gained universal acceptance or been validated for use in a paediatric population. Until recently, the most widely used criteria were those developed by the American-European Consensus Group. It remains well-recognised that international consensus on classification is important for standardisation, particularly in relation to research and monitoring treatment outcomes. With this in mind, the 2016 ACR/EULAR criteria were developed. However, there still remains a paucity of validated classification criteria for diagnosis of juvenile-onset pSS. Paediatric-focused criteria are required as features of pSS in children differ from those observed in adults. Children experience less dryness and more frequently experience systemic symptoms and parotid enlargement. Hence, simply applying adult criteria to a paediatric population may lead to mis- and/or under-diagnosis. The overarching aim of this study is to identify epidemiological, clinical and laboratory characteristics of PpSS in a multi-centre cohort of patients. Using this data our goal is to develop universally accepted classification criteria validated for use in a paediatric population. Going forward, this would enable standardisation of PpSS classification allowing for robust studies into disease pathogenesis, management and prognosis. Methods Inclusion criterion for entry into the UK/Ireland PpSS cohort study and repository is diagnosis of pSS before 18 years. A data collection pack will be sent to authors willing to participate. Information collected will include demographic, clinical and laboratory/histological data at diagnosis and subsequent follow-up appointments. Biological samples including blood, tears, saliva, urine, and glandular and extra-glandular (e.g. renal) tissue will be collected prospectively if available. Outcome measures related to disease activity and damage, as well as patient reported outcomes will also be collected at set time-points. Results No results to report. Conclusion The UK/Ireland PpSS cohort study and repository will capture data on a significant cohort of children with pSS providing a powerful resource to help improve our understanding of this rare disease. Prospective data collection will allow a fuller analysis of poor prognostic features, impact of therapy, damage accrual and variable outcome of PpSS. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background An estimated 10-20% of all patients with systemic lupus erythematosus (SLE) develop clinical disease before the age of 18 years and are therefore classified as juvenile-onset SLE (JSLE). JSLE patients have a higher prevalence of lupus nephritis (LN) compared to adult-onset SLE and decreased long-term survival compared to JSLE patients without LN. We aimed to identify clinical and laboratory predictors of LN in JSLE patients by comparing the baseline characteristics of JSLE patients with and without LN. Methods This is a single-centre retrospective study that included JSLE patients reviewed in our young adult and adolescent clinics after transitioning from paediatric services. All data was analysed descriptively. Mann-Whitney U or Chi-square test were performed to compare the characteristics between patients with and without LN. In addition, we performed uni- and multivariate analysis to investigate potential predictor biomarkers for LN. Results We identified 134 JSLE patients, 45 (34%) of which had LN. 112 (83.6%) of the patients were female and the median age was 22 years (interquartile range [IQR] 20- 24). The median disease duration was longer in the patients with LN (10 years [IQR 8- 14]) in comparison with the patients without LN (8 years [IQR 6- 13]), p = 0.012. As expected, the highest dsDNAlevels ever were observed in patients with LN (p = 0.022). The overall clinical manifestations and complications did not differ between JSLE patients with or without LN, except for the prevalence of low bone mineral density. 16 (35.5%) patients with LN had low bone density and only 11 (12.4%) patients without LN (p = 0.008). Factors associated with low bone mineral density in a univariate logistic regression analysis were: the use of mycophenolate mofetil (p = 0.021) and the presence of LN (p = 0.007), while LN also associated with low bone density (p = 0.008) in a multivariate analysis. Skin involvement was the most common clinical manifestation in both JSLE patient groups. Treatment was more aggressive in patients with LN, including the use of cyclophosphamide, mycophenolate and rituximab, but there was no difference regarding the length of the steroid treatment. The majority of patients (67%) had one flare of nephritis. For the remaining patients, the number of flares ranged from 2 (13%) to 12 (2.2%). The class of nephritis was reported in 34 out of 45 patients, and focal lupus nephritis (class III) was the most common type (44%) reported. There were no statistically significant differences in the baseline characteristics or treatments among the different classes of LN. Conclusion Low bone mineral density in patients with JSLE is well described. However, this is the first study highlighting the association of low bone density with LN independent of total duration of steroid treatment or other clinical manifestations. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]