Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles

ObjectivesDrug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still’s disease with atypical lung disease. We sought to characterise features of patients with Still’s disease with DRESS compared with drug-tolerant Still’s controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort.MethodsIn a case/control study, we collected a multicentre series of patients with Still’s disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still’s controls (n=65). We retrospectively analysed clinical data from all Still’s subjects and typed 94/131 for HLA. European Still’s-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still’s cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still’s-DRESS cases (n=64) compared with drug-tolerant Still’s controls (n=30). KD subjects (n=19) were similarly studied.ResultsStill’s-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still’s-DRESS (64%) versus drug-tolerant Still’s (3%; p=1.2×10−14). We found striking enrichment for HLA-DRB1*15 haplotypes in Still’s-DRESS cases versus INCHARGE Still’s controls (p=7.5×10-13) and versus self-identified, ancestry-matched Still’s controls (p=6.3×10−10). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions.ConclusionsDRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted.

Patterns of etanercept use in juvenile idiopathic arthritis in the Childhood Arthritis and Rheumatology Research Alliance Registry

Background We aimed to characterize etanercept (ETN) use in juvenile idiopathic arthritis (JIA) patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods The CARRA Registry is a convenience cohort of patients with paediatric onset rheumatic diseases, including JIA. JIA patients treated with ETN for whom the month and year of ETN initiation were available were included. Patterns of ETN and methotrexate (MTX) use were categorized as follows: combination therapy (ETN and MTX started concurrently), step-up therapy (MTX started first and ETN added later), switchers (MTX started and then stopped when or before ETN started), MTX add-on (ETN started first and MTX added later), and ETN only (no MTX use). Data were described using parametric and non-parametric statistics as appropriate. Results Two thousand thirty-two of the five thousand six hundred forty-one patients with JIA met inclusion criteria (74% female, median age at diagnosis 6.0 years [interquartile range 2.0, 11.0]. Most patients (66.9%) were treated with a non-biologic disease modifying anti-rheumatic drug (DMARD), primarily MTX, prior to ETN. There was significant variability in patterns of MTX use prior to starting ETN. Step-up therapy was the most common approach. Only 34.0% of persistent oligoarticular JIA patients continued treatment with a non-biologic DMARD 3 months or more after ETN initiation. ETN persistence overall was 66.3, 49.4, and 37.3% at 24, 36 and 48 months respectively. ETN persistence among spondyloarthritis patients (enthesitis related arthritis and psoriatic JIA) varied by MTX initiation pattern, with higher ETN persistence rates in those who initiated combination therapy (68.9%) and switchers/ETN only (73.3%) patients compared to step-up (65.4%) and MTX add-on (51.1%) therapy. Conclusion This study characterizes contemporary patterns of ETN use in the CARRA Registry. Treatment was largely in keeping with American College of Rheumatology guidelines.

Principles of pediatric lupus nephritis in a prospective contemporary multi-center cohort

Lupus nephritis (LN) is a life-threatening manifestation of systemic lupus erythematosus (SLE) and is more common in children than adults. The epidemiology and management of childhood-onset SLE (cSLE) have changed over time, prompting the need to reassess expected outcomes. The purpose of this study is to use the Childhood Arthritis and Rheumatology Research Alliance (CARRA) prospective registry to validate historical principles of LN in a contemporary, real-world cohort. After an extensive literature review, six principles of LN in cSLE were identified. The CARRA registry was queried to evaluate these principles in determining the rate of LN in cSLE, median time from cSLE diagnosis to LN, short-term renal outcomes, and frequency of rituximab as an induction therapy. Of the 677 cSLE patients in the CARRA registry, 32% had documented LN. Decline in kidney function was more common in Black cSLE patients than non-Black patients ( p = 0.04). Black race was associated with worse short-term renal outcomes. In short-term follow up, most children with LN had unchanged or improved kidney function, and end stage kidney disease (ESKD) was rare. Ongoing follow-up of cSLE patients in the CARRA registry will be necessary to evaluate long-term outcomes to inform risk, management, and prognosis of LN in cSLE.

Telemedicine use by pediatric rheumatologists during the COVID-19 pandemic

Background To characterize various aspects of telemedicine use by pediatric rheumatology providers during the recent pandemic including provider acceptability of telehealth practices, clinical reliability, and clinical appropriateness. Methods An electronic survey was generated and disseminated amongst the Childhood Arthritis and Rheumatology Research Alliance (CARRA) listserv (n = 547). Survey items were analyzed via descriptive statistics by question. Results The survey response rate was 40.8% (n = 223) with the majority of respondents in an attending-level role. We observed that musculoskeletal components of the exam were rated as the most reliable components of a telemedicine exam and 86.5% of survey respondents reported engaging the patient or patient caregiver to help conduct the virtual exam. However, 65.7% of providers reported not being able to elicit the information needed from a telemedicine visit to make a complete clinical assessment. We also noted areas of disagreement regarding areas of patient engagement and confidentiality. We found that approximately one-third (35.8%) of those surveyed felt that their level of burnout was increased due to telemedicine. Conclusion In general, providers found exam reliability (specifically around focused musculoskeletal elements) in telemedicine visits but overall felt that they were unable to generate the information needed to generate a complete clinical assessment. Additionally, there were suggestions that patient engagement and confidentiality varied during telemedicine visits when compared to in-person clinical visits. Further qualitative work is needed to fully explore telemedicine use in pediatric rheumatology.

Inflammatory arthritis and arthropathy

Musculoskeletal pain from childhood-onset rheumatologic conditions such as juvenile idiopathic arthritis is variable in severity and impact. Advancements in understanding the mechanisms of inflammation causing arthritis and its associated pain have led to new treatments and guidelines for improved control of arthritis disease activity when implemented in a timely manner. In spite of these new treatments, pain often persists in childhood arthritis, even when little-to-no active inflammation is detected, highlighting the need to use a biopsychosocial model to address all factors contributing to pain symptoms. Using this holistic approach, we can better manage the pain of children with rheumatologic diseases in routine clinical practice, as well as in settings such as clinical trials and other treatment interventions.

OP0278-PARE PROVIDING SUPPORT TO FAMILIES OF CHILDREN NEWLY-DIAGNOSED WITH CHILDHOOD ARTHRITIS: A PATIENT AND PARENT-LED PILOT STUDY TO DEVELOP AND ASSESS ‘A LITTLE BOX OF HOPE’ SUPPORT PACKS

Background:Juvenile Idiopathic Arthritis (JIA) is a heterogenous group of autoimmune disorders characterised by chronic joint inflammation, diagnosed in around 1 in 1,000 children and young people (CYP) under the age of 16. Delays in diagnosis are common [1], awareness is low, and paediatric rheumatological conditions have a considerable impact on young people and their families [2]. A lack of understanding amongst families of newly-diagnosed children leads to uncertainty and anxiety.Objectives:This patient and parent-led project developed a resource pack for parents of CYP newly-diagnosed with JIA, to provide information and support. Following a pilot, feedback from recipients was collated and analysed to help improve future provision.Methods:A young person with JIA identified the need for direct family support. Juvenile Arthritis Research (a UK charity) developed a unique pack of support information, containing resources for both children and their families - called A Little Box Of Hope. This included information about JIA and support services available for families, as well as Kipo (a children’s book about JIA) and accompanying finger puppet. Clinicians at one paediatric rheumatology centre provided information about the packs to newly diagnosed families, who then requested a free box to be posted to them.Following an initial pilot study, recipients were invited to complete a short online questionnaire and provide feedback to allow refinement of the provision.Results:Respondents were asked a series of questions, each on a scale of 1-5. Every respondent gave a score of 5 in response to “What do you think of the idea of A Little Box Of Hope?”Every parent of children under ten years old gave a score of 5 for every item when asked “How useful is each item in your Little Box Of Hope?”Respondents also gave free-text comments:* “It was very well thought out and I felt supported”* “I know so much more about JIA now than I did before. I cannot thank you enough.”* “It was extremely useful and made me feel supported during a very stressful time and this enabled me to support my son more effectively.”* “It made my daughter feel less alone.”Some parents of older children felt that some information specifically for teens would be useful, and a Teen pack is being developed.Conclusion:Recipients of A Little Box Of Hope have found the information useful and feel supported. Following the pilot study, we have developed My JIA, a booklet reviewed by a multi-disciplinary clinical team, with comprehensive information for families affected by JIA. A Teen pack, for children aged around 10 years or older, is being developed to provide targeted support to this group.The COVID-19 pandemic has adversely affected access to healthcare services, increasing the need for remote parent- and charity-provided support through A Little Box Of Hope.As such, we intend to expedite the roll-out of the project across the country building on the success of the pilot project.References:[1]McErlane F, Foster HE, Carrasco R, et al. Trends in Paediatric Rheumatology Referral Times and Disease Activity Indices over a Ten-Year Period among Children and Young People with Juvenile Idiopathic Arthritis: Results from the Childhood Arthritis Prospective Study. Rheumatology (Oxford) 2016;55(7):1225–34.[2]Foster HE, Scott C, Tiderius CJ, et al. Improving Musculoskeletal Health for Children and Young People - A “Call to Action”. Best Pract Res Clin Rheumatol 2020;34(5):101566.[3]Dejaco C, Alunno A, Bijlsma JWJ, et al. Influence of COVID-19 Pandemic on Decisions for the Management of People with Inflammatory Rheumatic and Musculoskeletal Diseases: A Survey among EULAR Countries. Ann Rheum Dis 2020;0:1-9.Disclosure of Interests:None declared