OBJECTIVES:To evaluate humoral immune response to recombinant zoster vaccine (RZV) in immunosuppressed patients with SSc compared with healthy controls, to identify factors influencing vaccine response and to assess RZV safety and impact on patient-reported outcome measures (PROMs) and disease activity (DA). METHODS:A sub-analysis of a randomized, double-blind, placebo-controlled trial included 76 immunosuppressed SSc patients and 304 healthy controls (CG) receiving two RZV doses. SSc patients were randomized to receive two initial doses of RZV or placebo; after unblinding, the placebo group received two doses of RZV. Anti-glycoprotein-E antibodies were measured at baseline and 6 weeks post-second dose. Geometric mean concentrations (GMCs) and factor increase (FI) were calculated. Cell-mediated immunogenicity (CMI) was evaluated. DA and PROMs were assessed using standardized instruments. BMI defined nutritional status. RESULTS:SSc patients(47.4%diffuse/52.6%limited) were younger (53.0 vs 55.0 years, P = 0.002) and had lower BMI (P = 0.005) than CG. Humoral response was significantly lower in SSc compared with the controls (92.6% vs 99.7%, P = 0.001). SSc patients showed significantly lower GMC (5.81 vs 12.6, P < 0.001) and FI (31.0 vs 59.4, P < 0.001) than the controls, with comparable CMI (P > 0.05). Disease subtypes, demographic factors, immunosuppressive therapies or nutritional status did not predict impaired vaccine response (P > 0.05). Local adverse events were reduced in SSc patients (73.7% vs 86.5%, P = 0.024), while systemic reactions were comparable overall (59.2% vs 61.5%, P = 0.712). DA and PROMs outcomes remained stable (P > 0.05). CONCLUSION:RZV was well tolerated. Despite the high seroconversion rate, the immune response was significantly lower in magnitude compared with the controls, without triggering DA or worsening PROMs. About ∼50% lower antibody concentrations in SS raise concerns about long-term protection, underscoring the need for ongoing monitoring. TRIAL REGISTRATION:ClinicalTrials.gov; NCT05879419.

OBJECTIVE:To develop evidence-based Pan American League of Associations for Rheumatology (PANLAR) recommendations for the treatment of oligoarthritis category in juvenile idiopathic arthritis (oligo-JIA) patients. METHODS:A panel of pediatric rheumatologists from Latin-America (LATAM) generated clinically meaningful questions related to the treatment of oligo-JIA patients, using Population, Intervention, Comparator, and Outcome (PICO) format. Following Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, a team of methodologists conducted a systematic literature review, extracted, summarized intervention effect estimates, and graded the evidence quality. LATAM pediatric rheumatology experts' panel voted each PICO question, which required a minimum agreement of 70% among the voting members and developed recommendations. RESULTS:Seven recommendations and 4 expert opinion were developed. Short-term course of NSAID and intra-articular corticosteroids was recommended as initial therapy in those with minimal disease activity with no risk factors for poor prognosis. The initiation of a nbDMARD was recommended in patients with high disease activity and risk factors for poor prognosis. For patients who achieve inactive disease state, treatment with DMARD should be maintained for a minimum of 12 months after remission. We proposed sulfasalazine or leflunomide in patients with methotrexate intolerance, or in the presence of contraindication or unavailability of bDMARD. For oligo-JIA patients with high disease activity or uveitis, anti-TNF agents are recommended as the first choice among bDMARD. Regular physical activity was also recommended for these patients. CONCLUSIONS:The first PANLAR oligo-JIA treatment guidelines provide evidence-based guidance for health care providers, treating patients with oligo-JIA in LATAM.

OBJECTIVES:Tofacitinib is a Janus kinase inhibitor studied in different categories of juvenile idiopathic arthritis (JIA). This post hoc analysis evaluated the impact of tofacitinib on the growth of patients with JIA and on biomarkers of growth hormone (GH) function and bone metabolism. METHODS:The analysis included 225 patients, primarily with polyarticular-course JIA, receiving long-term tofacitinib (median [IQR] follow-up 3.6 [1.9-4.6] years). Height velocities (cm/y) and height Z-scores (based on age- and sex-matched reference data) were calculated. Biomarkers were measured in serum from 137 patients with JIA completing 18 weeks of open-label treatment with tofacitinib. RESULTS:This population of patients with JIA had a baseline height distribution similar to the general population. During treatment with tofacitinib, patients experienced height velocities that appeared greater (patients ≤12 years) or as expected (patients >12 years) relative to the reference for their ages. Height Z-scores were largely stable during treatment with tofacitinib. In patients in puberty and a height Z-score less than --1.0 at baseline, an increase in height Z-score (P < .05) was detected after 24 months of treatment. Tofacitinib treatment did not impact levels of insulin-like growth factor (IGF)-1, IGF binding protein 3 and osteocalcin in the overall population, but in patients aged 6 to 12 years, IGF-1 levels increased with tofacitinib from baseline to 18 weeks. CONCLUSIONS:This post hoc analysis of patients with JIA indicated normal or higher than expected growth velocity during long-term treatment, with tofacitinib with catch-up growth during puberty and, overall, no concerning changes in biomarkers of GH signalling.

OBJECTIVE:To evaluate the immunogenicity and safety of the recombinant zoster vaccine (RZV) in immunosuppressed patients with idiopathic inflammatory myopathies (IIM), with particular focus on its impact on disease activity. METHODS:This subanalysis of a randomized, double-blind, placebo-controlled study included 70 immunocompromised adult patients with IIM (2017 ACR/EULAR criteria) and 280 healthy controls (control group [CG]), who received two RZV doses. Seroconversion was defined as a ≥4-fold increase in anti-gE antibodies. Geometric mean titers (GMT) and factor increase (FI) were assessed, and multivariable regression analyses were performed to identify factors associated with seroconversion. Patients were randomized 1:1 to receive RZV or placebo during the blinded phase, and disease activity was evaluated using validated instruments (visual analog scale, the Myositis Disease Activity Assessment Visual Analog Scale, Manual Muscle Test-8 (MMT-8), Health Assessment Questionnaire, and the modified Medical Research Council dyspnea scale and serum muscle enzymes. RESULTS:Patients with IIM were younger (53 vs 55 years, P = 0.005) and had a higher prevalence of previous herpes zoster (36.7% vs 13.3%, P < 0.001) than CG. Seroconversion rates were lower in IIM compared with CG (83.3% vs 99.3%, P < 0.001), with reduced post-vaccination GMT (6.4 vs 11.8 mIU/mL, P = 0.001) and FI-GMT (21.8 vs 53.0, P = 0.001). Mycophenolate mofetil use, higher baseline cutaneous activity, and higher baseline GMT were independently associated with reduced seroconversion (P < 0.05). Adverse events, mostly mild, were reported by 35 of 70 (50.0%) patients with IIM and by 204 of 280 (72.8%) CG (P < 0.001). No differences in activity scores were observed between vaccine and placebo groups (P > 0.05). CONCLUSION:RZV was safe and induced seroconversion in most immunosuppressed patients with IIM, without evidence of vaccine-related disease activation. Attenuated antibody responses, particularly in patients receiving mycophenolate mofetil or with active cutaneous disease, support individualized vaccination strategies to optimize protection in this high-risk population (ClinicalTrials.gov NCT05879419).

OBJECTIVE:A data-driven and expert/patient consensus-based project to develop a revised Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) is under way supported by SLICC, ACR, and the Lupus Foundation of America. Our objective is to report the item generation and reduction phase results for a revised SDI. METHODS:Item generation included a literature review by literature review groups and a Delphi exercise of international systemic lupus erythematosus experts and patients. Item reduction involved Delphi rounds in which items with a median appropriateness score of ≤4 of 9 were excluded. A 14-member item reduction committee assessed remaining items and removed those that did not reflect the damage construct, were rare, or were not feasible to assess. The clinical domain groups then refined the remaining items and their definitions. RESULTS:The Delphi panel included 146 individuals from 35 countries. The Delphi exercise nominated 2,256 items, and the literature review identified 117 items. After removing redundancies, 226 candidate items remained. Subsequent Delphi rounds, followed by review by the item reduction committee and clinical domain groups, resulted in 39 items across 13 domains. Eleven items from the original SDI, including proteinuria and cranial neuropathy, were removed and several new items were proposed, including growth failure/reduced final height and adrenal insufficiency. Severity-based subitems are proposed for 17 items (43.6%). CONCLUSION:This data-driven and expert/patient consensus-based process has proposed 39 candidate items, some with subitems, and definitions for a revised SDI. Weighting of items and subitems is underway to develop a clinical scoring system.

Background Lupus nephritis is an uncommon severe glomerulonephritis which on kidney biopsy is classified into class I-V. The aim of this study was to describe differences in presentation, treatment and outcome between children with the different biopsy classes. Methods We compared, in a cohort of 428 children, clinical and laboratory data at onset, two-year and last follow-up (median of four years and four month) between children with the different biopsy classes. Results The number of children with the biopsy classes III, IV, V and mixed V and III or IV, were 132, 191, 43 and 62 respectively. At onset did children with a biopsy pattern of class III and IV show lower haemoglobin levels, 99 and 96 g/L, vs 104 and 112.5 g/L, respectively and lower complement C3 levels 0.37 and 0.35 g/L vs 0.44 and 0.59. Levels of double stranded DNA antibodies (dsDNA) and ESR showed no statistically significant differences between the groups. Reduced eGFR was found significantly more often in children with class IV compared to the other groups of children. Children with mixed class V and III or IV had the highest levels of proteinuria and lowest serum albumin levels. Treatment of the children in the different groups was mainly similar with the exceptions of less frequent use of initial methylprednisolone and cyclophosphamide in children with pure class V. At two years and last follow up no differences in neither inflammatory parameters nor complement and dsDNA levels were found. eGFR was also not significantly different at follow-up while between 9.6 and 31.9 percent of the children still showed impaired kidney function. Children with class V combined with III or IV did most often show continuing proteinuria. Discussion At onset children in the biopsy classes with proliferative glomerulonephritis showed more haematological signs of inflammation while those with class V, membranous nephritis, had higher levels of proteinuria. Children with mixed biopsy phenotypes showed a combination of these findings. Treatment and outcome were however surprisingly similar in children from all biopsy groups.

ObjectiveTo report pharmacokinetics (PK), immunogenicity, clinical effect, and safety of intravenous (IV) golimumab in children with active polyarticular-course juvenile idiopathic arthritis (pcJIA) who participated in A Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Intravenous Golimumab in Pediatric Participants With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy (GO-VIVA)’s open-label, long-term extension (LTE) through week 252.MethodsGO-VIVA participants who continued IV golimumab (80 mg/m2every 8 weeks) after week 52 were included. PK and safety were assessed through week 244 (last dose) and week 252, respectively, and clinical response through week 116. Clinical outcomes included JIA–American College of Rheumatology (ACR) responses and clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10). Binary outcomes used nonresponder imputation, and other descriptive analyses used observed data.ResultsOf 112/127 (88.2%) participants entering the LTE, 69 completed the week 252 visit. Median steady-state trough golimumab concentrations were generally maintained from week 52 through week 244 (range 0.3-0.6 μg/mL). Antigolimumab antibody rates were consistent through week 52 (39.2% [49/125]) and week 244 (44.8% [56/125]). Week 52 JIA-ACR 30/50/70/90 response rates (75.6% [96/127], 74% [94/127], 65.4% [83/127], and 48.8% [62/127], respectively) were generally maintained through week 116 (72.4% [92/127], 71.7% [91/127], 63.8% [81/127], and 50.4% [64/127], respectively), when the median cJADAS10 was 1.6 and 56.7% (72/127) of participants achieved cJADAS10 ≤ 5 (minimal disease activity). Rates (per 100 patient-years) of serious adverse events and serious infections through week 252 were 7.7 and 3.9, respectively.ConclusionGO-VIVA LTE participants experienced adequate PK exposure and stable safety and immunogenicity. The majority of participants experienced no more than minimal residual disease activity. Data suggest IV golimumab treatment provided durable clinical response through week 116, with an acceptable risk-benefit profile.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, but its outcomes are still difficult to determine. We aimed to obtain outcome measurements of disease activity, functional capacity, disease damage, and therapeutic response, at one-year follow-up study on a real-life basis. An observational JIA cohort from two referral centers for pediatric rheumatology in Brazil Pediatric Rheumatology Centers was carried out over a period of one year. Clinimetric validated outcome measurements were applied over four visits. Multivariable logistic regression was performed to evaluate baseline variables associated with the following outcomes after one year of follow-up: disease activity, Minimal Disease Activity (MDA), disease flare, remission on medication and remission off medication. A total of 127 patients were included in the study. Eighty-three (65.4

Patients with autoimmune rheumatic diseases (ARDs) are at an increased risk for herpes zoster (HZ). Vaccination is recommended for this population. The aim of this study was to evaluate the safety of vaccination with the recombinant zoster vaccine (Shingrix) in ARD patients, humoral immunogenicity (HI), cellular immunogenicity (CI), and the incidence of HZ. This randomized, double-blind, placebo-controlled phase 4 study involves 1180 ARD patients and a control group (CG) of 393 balanced healthy individuals, aged ≥50 years. ARD patients will be randomly assigned in a blinded manner (1:1 ratio) to 2 groups: vaccine or placebo (on days 0 and 42), administered intramuscularly. Outcomes will be assessed at baseline, 6 weeks, and 12 weeks after vaccination, including disease activity (using specific disease activity scores), HI, and CI. Adverse events will be assessed using a standardized questionnaire after each vaccine dose. Incident HZ cases will be monitored throughout the study. One year following the second dose, the persistence of HI and CI will be evaluated in both ARD patients and CG. HI and CI will be assessed using serum concentrations of anti-gE antibodies and the frequencies of gE-specific CD4+ T cells, respectively. Comparisons of anti-gE titers between ARD patients and CG at different time points will be analyzed using 2-way repeated-measures analysis of variance. Multiple regression analysis will be conducted, with a positive immune response as the dependent variable, and variables with p < 0.2 from univariate analysis as independent variables. This large trial addresses a critical gap by examining disease safety, efficacy, adverse effects, and immunogenicity, considering the impact of diverse therapies following recombinant zoster vaccine administration in ARD patients.

PT005 / #801 Topic: AS17 - Miscellaneous POSTER TOUR 01: CLINICAL OUTCOMES IN SLE 22-05-2025 10:00 AM - 10:40 AM Patients with autoimmune rheumatic diseases (ARDs) are at high risk of herpes zoster (HZ) and the new recombinant vaccine against HZ (RZV) offers safety improvements. This study evaluates disease safety, overall safety and humoral immunogenicity of RZV in ARD patients compared to nonvaccinated ARDs and nonimmunosuppressed control group (CG). This prospective double-blind randomized placebo-controlled phase 4 study evaluated ARD patients at high risk of HZ. Participants aged >18 years were randomized into 2 groups: P1 (vaccine) and P2 (placebo), with nonimmunosuppressed individuals serving as CG. Both P1 and CG received 2 intramuscular doses of RZV administered 6 weeks apart (D0 - V1 and D42 - V2), while P2 received placebo. Disease activity was evaluated using specific scores and adverse events (AEs) were assessed through a standardized questionnaire. Blood samples were collected prior to the 1st dose (V1) and 6 weeks following the 2nd dose (V3) with humoral immunogenicity measured via anti-gE antibody serum concentrations (ELISA). A total 1,012 ARD patients (P1:529 and P2:483) and 393 CG completed the study. ARDs included 9 different chronic conditions, mainly rheumatoid arthritis (n = 290) and systemic lupus erythematosus (n = 302). At baseline, treatments included prednisone (39%), hydroxychloroquine (31%), sulfasalazine (6%), immunosuppressive drugs (79%) [mycophenolate mofetil (24%), methotrexate (23%), leflunomide (20%), azathioprine (18%) and cyclosporine (2%), tacrolimus (2%) and cyclophosphamide (3%)], biologic therapy (44%) [TNFi (17%), tocilizumab (8%), rituximab (7%), belimumab (6%), secukinumab (5%) and anifrolumab (1%)] and JAK inhibitors (4%). P1(vaccine) and P2 (placebo) groups were balanced for age [50 (IQR 39.8 - 61) vs 51 (IQR 40 - 61.8) years, p = 0.543], female sex (77% vs 80%, p = 0.314), ARD diagnoses and therapies (p > 0.05), except for lower frequency of mycophenolate mofetil (MMF) in P1 (p = 0.047). The primary endpoint showed comparable flare frequencies in P1 and P2 at V2 (4.1% vs 6.2%, p = 0.142) and V3 (10.2% vs 11.6%, p = 0.506). Secondary endpoints revealed no moderate/severe AEs, but AEs were less frequent in P1 (78% vs 90%, p < 0.0001), including both local (72% vs 85% p < 0.0001) and systemic reactions (50% vs 62%, p = 0.001), mainly headache (24% vs 33%, p=0.005), fatigue (16% vs 24%, p = 0.008), drowsiness (16% vs 23%, p = 0.015), myalgia (16% vs 21%, p = 0.034), chills (15% vs 21%, p = 0.012) and fever (11% vs 19%, p=0.002) after 1st RZV dose. Although humoral response was adequate, it was lower in P1 compared to CG (92% vs 99%, p < 0.0001). Baseline GMT was similar (p = 0.674), but the GMT increase after 2 doses was lower in P1 than in CG [35.09 (95%CI 30.49-40.4) vs 64.52 (95%CI 55.97-74.38); p < 0.001]. Multivariate analysis identified rituximab [OR 0.152 (95%CI 0.059-0.393), p < 0.0001] and MMF [OR 0.0460 (95%CI 0.224-0.946), p = 0.035] as major deleterious factors for reduced vaccine response. No HZ case were confirmed by RT-PCR up to week 12. RVZ demonstrated a strong disease safety profile and adequate short-term immunogenicity in highly immunosuppressed ARD patients, including those with active diseases, with no severe adverse events and no significant impact on disease activity. Our findings highlight MMF and rituximab as key factors impairing vaccine immunogenicity, suggesting that a booster dose may be beneficial for patients on these therapies.

OBJECTIVE:Despite the lack of science-based evidence, many specialists and non-specialists consider W-sitting detrimental to children. This systematic review aims to find evidence on W-sitting. METHODS:This review was registered on PROSPERO under the number CRD42022313341. During January 2023, the term "W-sitting" and its variations were searched on the following databases: PubMed, Medline, Embase, PEDro, and Cochrane. Duplicate articles and those that addressed themes other than W-sitting were removed. RESULTS:This review found 3641 articles, removed 614 duplicates, and excluded 3021 for focusing on subjects other than W-sitting. It included seven studies for analysis, one of which was a narrative review and two were methodologically inadequate cross-sectional to evaluate the causal effect in W-sitting. Another article evaluated muscular activation in adults according to sitting position. The last article found no causal relation between W-sitting and developmental dysplasia of the hip. CONCLUSION:This review found no scientific evidence advise against W-sitting in children and no association with hip dysplasia. Moreover, muscular activation remains the same, regardless of the position chosen for sitting. Level of evidence III, review article.

Objective: To identify clusters of autoantibodies in a large cSLE population and to verify possible associations between different autoantibody clusters and the following variables: demographic data, cumulative clinical and laboratory manifestations, disease activity, cumulative damage and mortality. Methods: A cross-sectional study was performed in 27 Pediatric Rheumatology University centers, including 912 cSLE patients. The frequencies of seven selected autoantibodies (anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-Sm, anti-RNP, aCL IgM and/or IgG and LA) were used for cluster analysis using the K-means method. Results: Four distinctive antibody clusters were identified. Cluster 1 (n = 322; 35.31%) was characterized by anti-dsDNA (61.18%), low frequency of antiphospholipid antibodies (<10%), and lower frequency of cutaneous, articular manifestation (p < 0.05) and hypocomplementemia (p < 0.001) compared to the other groups. Cluster 2 (n = 158; 17.32%) comprised anti-dsDNA (93.04%), aCL (87.34%) and LA (39.87%) and higher frequencies of thrombocytopenia (p = 0.006) and antiphospholipid syndrome (p < 0.001) than the other clusters. Cluster 3 (n = 177; 19.41%) was characterized by anti-dsDNA (81.36%), anti-Sm (100%) and anti-RNP (44.63%) antibodies, as well as a higher frequency of proteinuria compared to cluster 4 (58.15% vs 56.13% vs 64.00% vs 49.80%, p = 0.031). Cluster 4 (n = 255; 27.96%) consisted of all 7 autoantibodies, with predominance of anti-dsDNA (72.55%), anti-Ro/SSA (89.8%) and anti-La/SSB (45.88%), with no specific clinical pattern, except by higher pulmonary damage (p = 0.017). Conclusions:Our study suggests that, within the context of cSLE, the coexistence of anti-dsDNA with antiphospholipid autoantibodies is linked to an elevated incidence of antiphospholipid syndrome. This association does not coincide with a proportionate increase in the occurrence of nephritis. Conversely, the cluster of anti-dsDNA with anti-Ro/SSA and anti-La/SSB antibodies was associated with pulmonary damage, requiring close surveillance.