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Childhood Chronic Idiopathic Uveitis (cCIU) is a severe ocular condition that account for the 40% of uveitis in children. Its timely and proper treatment is critical to prevent severe complications. The purpose of this study was to describe the treatments of a large cohort of cCIU. This is a retrospective medical chart review study of cCIU followed at Meyer children's hospital IRCCS and Bristol Royal hospital for children (1st Jan2019 - 31st Jan 2020). Children were included if they have a diagnosis of CIU prior to 16 years old according to SUN. We collected demographic, clinical and laboratory data. Achievement of remission on treatment was evaluated as persistent inactivity for at least 3 months without drops and systemic corticosteroids. Data about 126 cCIU (61 female, median age at onset 9.3 years (3-16), ANA positive in 33 (77.6%)) were collected. 68 have anterior uveitis, 29 intermediate, 15 anterior + intermediate, 1 posterior and 13 panuveitis. Excluding the patient with posterior involvement, 97 children (77.6%) underwent to at least one systemic treatment, 65 (52%) to two, 18 (14.4%) to three and 2 (1.6%) to four (Infliximab and tacrolimus), with a median follow-up of 46 months (IQR 22-67). The first drug was administered after a median time of 5 months (IQR 2-10). Treatments performed were summarized in table 1. Among the first line treatment, children treated with adalimumab are more likely to achieve remission and maintain remission for a longer time after drug withdrawal compared to the other drugs (χ² 7.59 p 0.006 and p 0.036 respectively). No significant differences have been evaluated stratifying analysis for anatomical subtype, ANA status, ethnicity, sex, ESR and CRP at onset for achievement remission with the first line treatment. However, patients treated with methotrexate who did not achieve remission have lower visual acuity in LogMar (0.53 vs 0.36, Mann-Whitney U test p 0.02). The superiority of Adalimumab in terms of remission achievement was confirmed when it was used as second line treatment too (χ² 6.29 p 0.04), however they relapsed more frequently out of therapy (χ² 6.6 p 0.03). Moreover, with the II line treatment, panuveitis showed higher proportion of remission achievement with adalimumab and worse response to MMF (χ² 2 p 0.03). Treatment of cCIU is extremely challenging, achieving remission with the first line treatment in only the 50% of patients. However, patients treated with adalimumab have better chance to achieve remission and patients who showed worse visual acuity at onset would benefit of a more aggressive treatment with biologics since onset. NIL. NIL. Ilaria Maccora: None declared, Catherine Guly Consultant of: Eli Lilly and Company, Cinzia De Libero: None declared, Roberto Caputo: None declared, Athimalaipet Ramanan Speakers bureau: Speaker fees – Abbvie, Roche, UCB, Lilly, Novartis and SOBI, Consultant of: Consulting fees from Abbvie, Eli Lilly, UCB and Alimera, Employee of: Participation on a Data Safety Monitoring Board or Advisory Board: Eli Lilly, Gabriele Simonini: None declared. Table 1Treatment performed in cohort of Childhood CNIUTreatmentFirst Course of Systemic treatmentSecond course of systemic treatmentThird course of Systemic treatmentOverall(97)Mtx(89)MM(1)ADA(7)*P valueOverall(65)Mtx(6)ADA(45)MM(14)P valueOverall(18)ADA(16)MM(1)IFN (1)P valueConcomitant therapy*2 MTX41 MTX and 2 MM (Group ADA)11 MTX, 5 MMF, 1 AZATime of administration median (IQR)5(2-10)5(2-9)410(3-24)NS15 (8.25-27)44.5 (35.2-53.5)12(7-19.5)16(7.7-32)<0.00143.5(327-55)47 (12-90)4827NsDuration of therapy23(10-36)24 (11-38)522(7-24)NS24 (11.25-34.75)21.5 (9.7-26)23(11.2-32.7)33.5(6.5-52.5)NS19 (7-33)21.6 (2-55)255NsAchievement of remission on therapyN (%)45/90(50%)38/83-7/7χ² 7.59 p 0.00652/56(91.2%)5/638/399/12χ² 6.29 p 0.0414/15 (93.3%)13/14-1/1nsTime for achievement remission6(5-7)6(5-7.5)5(4-6.75)NS6(5-9)5 (4.5-7.5)6 (5-9)9(4-11.5)Ns6(4-9.25)6.6 (4-12)-9NsN of pts who stop drug for persistent remission23(25%)21/38-2/7NS26 (41.5%)3194NS3(18.7%)3/1500nsRelapse out of therapyN (%)13 (56.5%)12/21-1/2NS17 (63%)0152χ² 6.6 p 0.031/3(33.3%)1/3--nsTime free from relapse out of therapy3(2-21)3 (2-20)-40 (2-40)0.0366(3.75-9)4(2-4)6(4-9)6.5 (3.5-33.5)ns8(8-12)8(8-12)--NsList of abbreviations: ADA: adalimumab, MM: mycophenolate mofetil, MTX methotrexate, IFN: infliximab, N number, IQR interquartile range, NS non significant.

Background:The etiology and pathogenesis of juvenile idiopathic arthritis associated uveitis (JIA-U) and antinuclear antibody (ANA)-positive uveitis are poorly understood. Current treatments include topical steroid therapy and methotrexate (MTX), or biologic disease-modifying antirheumatic drugs (bDMARDs). However, patients commonly fail to achieve long-lasting remission with these medications (Sen et al. 2020). It is hypothesized that the use of baricitinib, through the inhibition of JAK-STAT signalling, could target multiple cytokine pathways associated with JIA-U and ANA-positive uveitis and may provide a novel therapeutic approach to disease management.Objectives:The aim of this study is to evaluate the efficacy and safety of baricitinib when administered to paediatric patients with active JIA-U or chronic anterior ANA-positive uveitis, who had an inadequate response to MTX or bDMARDs and are receiving topical corticosteroid eye drops at a stable dose.Methods:This open-label, active-controlled, Phase 3 trial, was conducted at 23 centres and included children from 2 to <18 years old. Patients received oral baricitinib once daily at age-based doses (2-<9 years old: 2 mg, 9-<18 years old: 4 mg). A reference group of patients received adalimumab by subcutaneous injection every 2 weeks (20 or 40 mg based on weight). The primary efficacy endpoint was the proportion of responders at Week 24 (W24), defined according to the Standardization of Uveitis Nomenclature (SUN) criteria as a 2-step decrease in the level of inflammation (anterior chamber cells) or decrease to zero through W24 in the eye most severely affected at baseline. A Bayesian analysis was performed for the primary endpoint, based on pre-specified success criteria (the posterior probability of the treatment response rate exceeding 57% is at least 80%). Safety evaluations of baricitinib in paediatric patients with JIA-U or ANA-positive uveitis included treatment-emergent adverse events (TEAEs). TEAEs were summarised using descriptive endpoints.Results:Among patients receiving baricitinib (N=24) the mean age was 11.6 (standard deviation [SD]: 3.5), 58.3% were female and the vast majority were White (Table 1). In the adalimumab group, the mean age was 6.6 years (SD: 2.5), 100% were female, and 80% were White (Table 1).Table 1. Baseline CharacteristicsAbbreviations: BMI = body mass index; ITT = intent-to-treat; N = number of patients in population; n = number of patients in specified category; SD = standard deviationThe primary endpoint of the study was not met. In the baricitinib group, 33% of patients achieved a response at W24, resulting in 1.03% posterior probability of a response rate of >57% (Table 2). The safety data, including the observed TEAEs in baricitinib treated patients with JIA-U and ANA-positive uveitis were consistent with the established safety profile in other baricitinib indications in paediatric and adult patients. In the baricitinib group, 83.3% of patients were reported with at least 1 TEAE of which 41.7% were mild, 29.2% were moderate and 12.5% were severe.Table 2. SUN Grade of Cells in the Anterior Chamber Response Rate at Week 24- mITT PopulationAbbreviations: bDMARD-IR = biologic disease-modifying antirheumatic drug-inadequate responder; mITT = modified intent-to-treat; MTX-IR = methotrexate-inadequate responder; N = number of patients in population; n = number of patients in specified category; N/A = not applicable; SUN = Standardization of Uveitis NomenclatureConclusion:The primary endpoint of the study was not met. The data provides additional information for the treatment of children with JIA uveitis refractory to both MTX and bDMARDs. Furthermore, baricitinib safety profile in this study was consistent with previous studies in children and adults with other diseases, with most TEAEs being mild or moderate.REFERENCES:[1] Sen ES, Ramanan AV. Juvenile idiopathic arthritis-associated uveitis. Clinical Immunology. 2020 Feb 1;211:108322.Acknowledgements:Caroline Murphy, Eli Lilly, for writing and editing support.Disclosure of Interests:Athimalaipet V. Ramanan Speakers fees from Eli Lilly, Abbvie, Pfizer, Roche, Novartis and SOBI, Consulting for Eli Lilly, UCB, Abbvie, Novartis, Astra Zeneca and Alexion, Unrestricted grant from Novartis for research, Catherine Guly Speaker at JUVE Bright Investigator meeting 2019, Assisted with writing protocol for JUVE Bright study, Gabriele Simonini Un-restricted educational grant from SOBI and NOVARTIS, Stuart Keller Stockholder in Eli Lilly and Company, retirement portfolio includes mutual funds that contain a proportion of holdings in pharmaceutical stocks, Salaried employee of Eli Lilly and Company, Priyanka Sen Shareholder of Eli Lilly, Employee of Eli Lilly, Thorsten Holzkaemper Shareholder of Eli Lilly & Company, Employee of Eli Lilly & Company, Pierre Quartier Speaker for Abbvie, BMS, Chugai-Roche, Novartis, Pfizer, Sweedish Orphan Biovitrum, Consulting for Abbvie, Amgen, BMS, Chugai-Roche, Lilly, Novartis, Novimmune, Pfizer, Sanofi, Sweedish Orphan Biovitrum, Grants from Abbvie, Amgen, BMS, Chugai-Roche, Lilly, Novartis, Pfizer, Sweedish Orphan Biovitrum.

pMCTD is a rare disorder that includes features of systemic lupus erythematosus, polymyositis/dermatomyositis, juvenile idiopathic arthritis, and systemic sclerosis. Fifty years have passed since Sharp identified MCTD in 1972, and diagnosis of this disorder remains challenging. The aim of this review is to identify any clinical features at the diagnosis of pMCTD and manifestations that are not currently part of the available diagnostic criteria. A systematic literature review was performed in accordance with PRISMA guidelines using electronic bibliographic databases: MEDLINE via PubMed and EMBASE. Data obtained were extracted using a dedicated database containing clinical data that best categorize patient characteristics. Criteria for inclusion: studies including patients with a pMCTD diagnosis with onset before 18 years of age and reporting a description of initial clinical features. The search returned a total of 1372 results: 409 articles were excluded as duplicates and 790 based on title/abstract, 133 because of publication type (n = 4) or because the full text was not available (n = 65) or not in English (n = 64). One (n=1) eligible article resulted from manual screening of references cited in the selected publications and in the reviews. Finally, 41 articles were included: 23 case reports, 9 case series, 5 prospective, and 4 retrospective studies from 1973 to 2019, with a total number of 218 patients. They were predominantly female (81.56%, n=167), and the mean age at onset was 147 months (median 126 months, 10.5 years). When indicated, the most commonly used criteria for diagnosis were Kasukawa criteria (50%, 11 studies), then Alarcon-Segovia criteria (31%, 7 studies), then Sharp criteria (23%, 5 studies); no Khan criteria were used. Clinical features are listed in Figure 1. Joint involvement, Raynaud's phenomenon, myositis, and swollen fingers/hands are the most common clinical features at diagnosis according to the data reported in the literature, although with slightly lower percentages than in other reviews. Dermatologic signs are very heterogeneous, but were found to be a very present feature at disease onset, affecting 1/3 of patients. Fever, not covered by any of the diagnostic criteria, was noted in 1/4 of cases. Pulmonary and esophageal involvement are reported in a lower percentage at the onset of the disease, indicating a more developmental nature of these conditions. The data from this systematic review suggest greater clinical heterogeneity of the disease in the pediatric population, for which there are no validated diagnostic criteria. Typical features appear to be less common when case reports are included, suggesting a less characteristic initial presentation than an advanced stage; therefore, the absence of typical features at baseline should not preclude a diagnosis of pMCTD. Fever often occurs early in the disease and is not included in the diagnostic criteria. This systematic review may provide useful insights for future research to better assess the clinical features of pMCTD and the potential development of scores/algorithms for diagnosis in the pediatric population. [1] Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR (1972) Mixed connective tissue disease–an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 52(2):148–159 [2] Singsen BH, Swanson VL, Kornreich HK, et al. Mixed connective tissue disease in childhood: a clinical and serologic survey. J Pediatr 1977;90:893– 900. [3] Fraga A, Gudino J, Ramos-Niembro F, et al. Mixed connective tissue disease in childhood. Am J Dis Child 1978;132:263– 5. [4] Kahn MF, Appelboom T. In: Kahn MF, Peltier AP, Meyer O, editors. Les Maladies Systemiques. Paris: Flammarion; 1991. p. 545–56. [5] Sharp GC, Kasukawa R, Alarcon-Segovia D, Villarreal M. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue diseases and anti-nuclear antibodies. Amsterdam: Excerpta Medica; 1987. p. 23–48. NIL. None Declared. [Display omitted]

Background:In 2021 we described the baseline clinical information about 887 FMF patients enrolled in the Eurofever registry since 2009.Objectives:We describe now first longitudinal data about these patients.Methods:Patients with FMF enrolled in Eurofever registry with at least one follow-up visit were included in a longitudinal study. Demographic and clinical data were analyzed. Disease activity and maximum dose of colchicine were defined according to the 2016 EULAR recommendation [1].Results:1104 patients with FMF are enrolled in Eurofever registry in November 2023, 574 males and 530 females. The median age at disease onset was 3.8 (0.4 - 28.1); the median diagnostic delay was 2.4 (0.1 – 28.7); the median age at enrollment was 7.9 (1.7 – 50.8). Follow-up information was available in 497 patients, with a mean number of follow-up visits of 2.2 (25th-75th centile 1-4) and a mean duration of follow-up of 5.4 years (range 2.2 – 8.2). At the last follow-up around half of patients in the longitudinal cohort were in complete remission, 34.9% experienced some disease activity (<1 episode/month) while only 9.2% experienced ≥ 1 episode/month and are therefore considered resistant to treatment according to the 2016 EULAR Guidelines (Table 1).At last follow-up visit 85.9% of patients of the longitudinal cohort were receiving colchicine, with a median duration of treatment of 4.4 years (0.4 – 15.4). Among resistant patients only 1 reached maximum recommended dose per age of colchicine according EULAR Guidelines (2 patients in partial remission, only 3 patients in complete remission). 8.2% of patients were on canakinumab while 0.4% were receiving anakinra. Among patients receiving biological treatments, 35 (81.4%) were receiving a combination of colchicine and biologics. Rate of withdrawal for colchicine were 10.3%, for canakinumab 6.5% while for anakinra was higher (61.1%). Reasons for withdrawal of treatment are detailed in Table 2.Conclusion:This study analyzes the initial data concerning the natural history of the Eurofever FMF cohort. At the last follow-up less than 50% of the patients have achieved complete disease control. Colchicine is the most used treatment. Among biologic drugs, IL-1 inhibitors are the most frequently used, with a good treatment retention rate at the last follow-up, especially for anti-IL-1 monoclonal antibody.REFERENCES:[1] S. Ozen et al., “EULAR recommendations for the management of familial Mediterranean fever,” doi: 10.1136/annrheumdis-2015-208690.Acknowledgements:This study is supported by a research collaboration agreement with Novartis.Disclosure of Interests:Marta Bustaffa: None declared, Gayane Amaryan: None declared, Romina Gallizzi: None declared, Efimia Papadopoulou-Alataki: None declared, Maria Carrabba: None declared, Jordi Antón: None declared, Gabriele Simonini: None declared, Maria Alessio: None declared, Luciana Breda: None declared, Jasmin B. Kuemmerle-Deschner: None declared, Donato Rigante: None declared, Laura Obici: None declared, Antonella Insalaco: None declared, Elizabeth Legger: None declared, Roberta Caorsi: None declared, Nicolino Ruperto Abbvie, Aclaris, Amgen, AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi, Marco Gattorno Novartis, Sobi, Seza Ozen: None declared.

Background:SAPHO syndrome is a rare autoinflammatory disease characterized in children by chronic non-bacterial osteitis (CNO), associated to a heterogenous dermatological involvement, ranging from Palmo-plantar pustulosis (PPP), to psoriasis vulgaris (PV), acne, hidradenitis suppurativa (HS), and pyoderma gangrenosum (PG). A recent study [1] suggested the existence of two different disease clusters in pediatric SAPHO syndrome (pSAPHO) based on skin manifestations: an acne-HS-PG group (male prevalence and disease onset in puberal age with skin manifestations refractory to multiple treatments) and a PPP-PV group (female prevalence and disease onset in prepuberal age with osteoarticular manifestations).Objectives:to confirm the presence of different disease clusters of pSAPHO in an italian multicentric cohort of patients, and to evaluate the efficacy of the different treatments in pSAPHO syndrome, compared to CNO.Methods:SAPHO patients were enrolled in the Eurofever Registry and the data retrospectively analysed. Patients with pSAPHO were divided into an acne-HS-PG group and a PPP-PV group, and were compared to a CNO group without skin manifestations. Comparison of frequencies between groups was performed by the means of the Chi-square test or by the Fischer’s Exact test.Results:43 pSAPHO patients with skin manifestations (32 acne-HS-PG and 11 PPP-PV) were enrolled and compared to 50 CNO. In the Acne-HS-PG group, 83.9% of the patients were males, with disease onset in puberal age with skin manifestations (median 13.7 years), and the appearance of osteoarticular symptoms in the following year in 81% of patients. In the PPP-PV group, 90.9% of patients were females, with disease onset in 100% of patients with osteoarticular manifestations in prepuberal years (median 10 years), and with the appearance of skin manifestations in the following year. In the CNO group there were no gender differences, with a median age at disease onset of 9.2 years. A statistically significant difference was found between the 3 groups in terms of sex (p< 0.0001), and between acne-HS-PG and PPP-PV and acne-Hs-PG and CNO for the age at disease onset (p< 0.0001) (Figure 1A). Moreover, a different osteoarticular involvement was evident in the 3 groups: all patients showed typical metaphyseal involvement, even if it was prevalent in the CNO group (86%, p=0.04), while an axial pattern (sterno-clavicular-spine-sacroiliacs) was more frequently present in the acne-HS-PG group (p<0.01), and a mandibular involvement in the PPP-PV group (p<0.01) (Figure 1b). The 3 groups presented also a different response to treatments: in the CNO group, NSAIDs, methotrexate and salazopyrin were more frequently used (p<0.05), and were efficacious in about 40% of patients, while 36% required bisphosphonates (BP), and 28% a biologic therapy. Similarly, in the PPP-PV group 30% of patients responded to NSAIDs alone, 30% to BP while 30% required the addition of a biological therapy. The skin responded well to the topical therapies or to DMARDs. In the acne-HS-PG group instead, there was a prevalent use of systemic steroids (50% of patients, p<0.05) and biological therapies (81% of patients, p<0.05). Among these, the combination Adalimumab/methotrexate was the more efficacious, with a remission achieved in 53% of patients. The skin resulted particularly difficult to treat in all the patients and was the cause of a therapy cycling.Conclusion:This study confirms the presence of 2 different disease clusters in pSAPHO based on the skin manifestations: an acne-HS-PG group characterized by a male predominance with puberal disease onset with skin manifestations particularly refractory to treatments, and a PPP-PV group characterized by female predominance with prepuberal disease onset with osteoarticular manifestations. These findings warrant a different therapeutical approach based on skin manifestations, and highlight the need of a new disease classification.REFERENCES:[1] Matucci-Cerinic C, et al. Semin Arthritis Rheum. 2023 Dec;63:152277.Figure 1.Acknowledgements:NIL.Disclosure of Interests:Caterina Matucci-Cerinic: None declared, Anna Attico: None declared, Clara Malattia: None declared, Alessandro Consolaro: None declared, Silvia Rosina: None declared, Luciana Breda: None declared, Saverio La Bella: None declared, Marco Cattalini: None declared, Francesca Ricci: None declared, Giovanni Conti: None declared, Adele Civino: None declared, Francesco Licciardi: None declared, Letizia Baldini: None declared, Antonella Insalaco: None declared, Francesco La Torre: None declared, Serena Pastore: None declared, Giovanni Filocamo: None declared, Gisella Beatrice Beretta: None declared, Gabriele Simonini: None declared, edoardo marrani: None declared, Angela Pistorio: None declared, Stefano Volpi SOBI, Roberta Caorsi: None declared, Nicolino Ruperto Abbvie, Aclaris, Amgen, AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi., Abbvie, Aclaris, Amgen, AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi., Gianmaria Viglizzo: None declared, Marco Gattorno Novartis, SOBI.

BackgroundJuvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. TNF inhibitors (TNFi) have dramatically changed the prognosis of this disease, but once achieved disease remission, it is not clear how and when stop therapy.ObjectivesOur purpose is to describe a multicentric cohort of JIA patients treated with the first course of Adalimumab and Etanercept in whom therapy was discontinued to persistent remission and identify predictors of relapse.MethodsIn a multicentric Italian retrospective study (Florence, Brescia, Trieste and Bari), patients with oligoarticular and polyarticular JIA were enrolled if they stopped therapy for persistent remission after the first course of Adalimumab and Etanercept. We collected demographic, clinical and laboratory data at onset and during biologic treatment.Results136 patients were enrolled (102 female, median age at onset 3 years (R1-15)), of whom 76 (55.9%) had oligoarticular JIA and 55 (40.4%) had uveitis. ANA positivity was found in 99(72.8%) (Table 1). TNFis were started at median age of 6 years (R1-16), with a median time intercourse between TNFi initiation and diagnosis of 12 months (0-127m). Seventy-nine (59.3%) were treated with ADA, and 57 (40.7%) with ETA. Remission was achieved after a median time of 4 months (R 1-32) and TNFi was discontinued after a median time of 30 months (R 6-90). TNFi were stopped in the 76.5% increasing the interval of administration, 18.4% reducing the dose, and 16.9% abrupt discontinuation. 106 patients (79.4%) relapsed after a median time of 6 months (R 0.5-96) for arthritis in 71 (66.9%), uveitis in 19 (17.9%), both in 18 (16.9%). Patients who relapsed were more frequently female (χ² 5.9 p<0.014), had history of uveitis (χ² 7.4 p<0.006), younger at onset (median 3 vs 7, p<0.001) and when TNFi was started (6 vs 9.5, p 0.002). Moreover, the time intercourse between diagnosis and TNFi initiation was longer (13 vs 8.5 months, p 0.02) and the weaned of therapy happened in shorter time (6 vs 9 m, p 0.005) (Table 1). Patients who not-relapse suspended TNFi more frequently lengthening intervals of administration (χ² 5.2 p0.015). Relapse free survival curve after withdrawal evaluated with Kaplan-Meier showed that patients with uveitis had a significantly earlier relapse (Log Rank χ² = 12.8 p <0.0001)ConclusionAlthough this is a retrospective study, we highlighted that early age at onset and at TNFi initiation, presence of uveitis and a long time to start biologics seem to be significantly more frequent in subjects who relapse, while stop therapy lengthening the interval of drug administration might be protective.Table 1.Characteristics of JIA patients after drug withdrawal (relapse Vs no-relapse)Entire cohort(136) n (%)Not relapse(28)Relapse(108)Test and p valueFemale n, %102 (75%)16 (57.1%)86 (79.1%)χ² 5.9 p 0.014Age at diagnosis, years, m (R)3 (1-15)7 (1-15)3 (1-11)p<0.001Uveitis history, n (%)55 (40.4%)550χ² 7.4 p<0.006Type of JIApOligo n (%)eOligo n (%)Poli n (%)55 (40.4%)21 (15.4%)60 (44.1%)12313431847nsANA positivity99 (72.8%)1683χ² 4.3 p 0.03Comorbdity n291019χ²4.35 p 0.037HLA B271467χ²3.9 p 0.048Type of BiologicsADA 79ETA 57ADA 13ETA 15ADA 66ETA 42nsCharacteristics at biologic starting and withdrawalAge at B initiation years, m, R6 (1-16)9.5 (1-15)6 (1-16)p0.002Concomitant therapy111 MTX (81.6%)20(71.4%)91(84.2%)χ² 6.58 p 0.03Time between diagnosis and B (months)12 (0-127)8.5 (0-117)13 (1-127)p0.021Time free from relapse out of therapy months6 (0.5-96)16 (4-96)5 (0.5-66)p<0.001Type of flareArthritisUveitisBoth71 (66.9%)19 (17.9%)18 (16.9%)-711918nsContinuation of concomitant therapy after stop B63339χ² 0.68 p 0.43N of months to stop B6 (0-22)9 (0-22)6 (0-22)p 0.005Modality to stop BLengthening intervalsReduction of doseAbrupt104 (76.5%)25 (18.4)16 (11.8%)26(92.8%)4178 (72.2%)2115χ² 5.2 p0.02Abbreviations: n number, m median, R range, pOligo persistent oligoarthritis, eOligo: extended oligoarthritis, Poli polyarticular, B biologic, ns: non significantREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundSystemic juvenile idiopathic arthritis (sJIA) accounts up to 15 % of all patients with JIA and is distinct from the other disease categories due to the association of articular and extraarticular manifestations. The systemic Juvenile Arthritis Disease Activity Score (sJADAS) is a composite disease activity score validated specifically for use in sJIA that includes, beside the four components of the original JADAS, a fifth item aimed to quantify the burden of systemic features. The interpretation of scores on sJADAS requires criteria that identify the states of disease activity. These criteria can be used to monitor the disease course over time and to define therapeutic targets.ObjectivesTo compare the clinical and laboratory data of each disease activity state in patients enrolled in the multinational study aimed to define the sJADAS cutoffs.MethodsData were extracted from a multinational cross-sectional dataset that included patients diagnosed as sJIA by ILAR criteria, recruited between February 2022 and November 2022. At study visit, each patient was categorized subjectively by the caring physician into one of the following disease activity states: inactive disease (ID), low (or minimal) disease activity (LDA), moderate disease activity (MDA), or high disease activity (HDA). Study data was collected through a standard case report form and entered into an electronic database.ResultsA total of 231 patients were enrolled in 29 centers in 12 countries. The mean age at diagnosis was 5.63 years. 87 patients (37.7%) were judged as having ID, 39 (16.9%) LDA, 46 (19.9%) MDA and 59 (25.5%) HDA. The comparison of the main clinical and laboratory features across patients with the four disease activity states is shown in the Table 1. Overall, the presence of extraarticular manifestations was more common in patients with MDA and HDA (P<0.00001), whereas fever, rash, hepatosplenomegaly, and lymphadenopathy were more frequent in HDA patients (<0.00001). The count of active joints increased progressively from ID to HDA (p<0.00001). The mean values of physician global assessment of disease activity and systemic manifestations, as well as the mean values of acute phase reactants, were highest in patients with HDA, with gradual decrease from MDA to LDA to ID.ConclusionThis preliminary analysis of the study data indicates that the subjective assessment of disease state by the caring physicians led to discriminate reliably patients with different level of disease activity. This evaluation will, then, serve well as reference for the subsequent analyses aimed to identify the cutoffs for the main disease activity states in sJIA.Reference[1]Tibaldi J, Pistorio A, Aldera E, et al. Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis. Rheumatology (Oxford). 2020 Nov 1;59(11):3505-3514.Table 1.Comparison of clinical and laboratory features across disease activity states (n = 231). ID=inactive disease; LDA= low (or minimal) disease activity; MDA=moderate disease activity; HDA=high disease activity; MD global VAS=physician global assessment of disease activity; MD systemic VAS= physician global assessment of systemic disease activity; ESR= erythrocyte sedimentation rate; CRP= C-reactive protein; NAJ=Number of active joints.IDLDAMDAHDANumber of patients (n, %)87 (37.7)39 (16.9)46 (19.9)59 (25.5)Age at onset, years (mean, SD)6.17 (4.24)5.44 (3.06)5.11 (3.42)5.36 (4.06)MD global VAS (mean, SD)1.08 (2.64)2.5 (2.59)5.03 (2.59)6.61 (2.91)MD systemic VAS (mean, SD)0.06 (0.23)0.88 (1.13)3.08 (2.69)7.52 (2.17)Systemic features (n,%)1 (1.1)7 (17.9)22 (47.8)56 (94.9)• Fever0 (0)0 (0)19 (41.3)55 (93.2)• Rash0 (0)4 (10.3)9 (19.6)29 (49.2)• Hepatomegaly0 (00 (0)2 (4.3)21 (35.6)• Splenomegaly0 (0)1 (2.6)4 (8.7)14 (23.7)• Lymphadenopathy1 (1.1)2 (5.1)5 (10.9)20 (33.9)• Serositis0 (0)0 (0)4 (8.7)9 (15.3)ESR, mm/h (mean, SD)8.46 (7.63)16.26 (14.43)46.11 (34.53)66.85 (32.4)CRP, mg/dl (mean, SD)0.39 (0.85)0.88 (1.93)5.17 (7.03)7.89 (6.06)NAJ > 1 (%)1 (1.1)13 (33.3)34 (73.9)53 (89.8)AcknowledgementsThis work was partially supported by the Fundación Española de Reumatología (FER).Disclosure of InterestsAna Isabel Rebollo Giménez: None declared, Yulia Vyzhga: None declared, Luca Carlini: None declared, Silvia Rosina: None declared, Elisa Patrone: None declared, Maria Katsikas: None declared, Claudia Saad-Magalhaes: None declared, Dalia El-Ghoneimy: None declared, Yasser El Miedany: None declared, Raju Khubchandani: None declared, Priyankar Pal: None declared, Gabriele Simonini Grant/research support from: educational grants from Abbvie, Sobi, Novartis, Giovanni Filocamo Consultant of: consultancies from Sobi and Novartis, Maurizio Gattinara: None declared, Fabrizio De Benedetti: None declared, Davide Montin: None declared, Adele Civino: None declared, Motasem O. Alsuweiti: None declared, Valda Stanevicha: None declared, Vyacheslav Chasnyk: None declared, Ekaterina Alexeeva Speakers bureau: speakers bureaus for Roche, Novartis and Pfizer., Grant/research support from: research grants from Roche, Pfizer, Centocor, Eli Lilly, AbbVie, Bristol-Myers Squibb, MSD, Sanofi, Amgen and Novartis., SULAIMAN AL-MAYOUF Speakers bureau: speaker fees from Sobi and Novartis, Soamarat Vilaiyuk: None declared, Angelo Ravelli Speakers bureau: from:Abbvie, Angelini, Pfizer, Novartis, BMS, Reckitt Benckiser, Sobi, Alexion, Roche.

Background:Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that mainly affects children and adolescents. Disease monitoring is challenging as reported pain is not reliable and imaging is not always obtained at all clinic visits. To date, patient reported outcomes used in CNO research have not yet been validated in this population. The Patient-reported Outcomes Measurement Information System (PROMIS) questionnaires, validated in other pediatric rheumatic diseases, are administered to patients enrolled in the prospective multisite CHronic nonbacterial Osteomyelitis International Registry (CHOIR)1 since 2018.Objectives:To assess the convergent and responsive validity of the PROMIS instruments in patients with CNO.Methods:Children or young adults with CNO were consented and enrolled into CHOIR. Self-reported PROMIS questionnaires of fatigue, pain interference (PI), pain behavior (PB), mobility, upper extremity (UE), physical activity (PA) and strength impact (SI) were administered to patients 8 years and older in English or Spanish at each clinical visit. Demographic, clinical, and imaging data were prospectively collected. The T score was calculated. External validation surveys were administered to assess patients’ perception of difficulty of use of limb/back/jaw, fatigue, sadness and worry on a 0-10 scale, disease status (inactive, mild, moderate, severe), and status change (unchanged, worsened, improved). Improvement of clinical disease activity score (CDAS) of 2.5 was defined as meaningful change. Descriptive statistics were used for demographic and clinical characteristics. Log-transformed linear mixed effect models with random participant intercepts were performed to assess PROMIS score changes after treatment. Wilcoxon signed-rank test with continuity correction was performed to determine the change of the PROMIS scores among the improved, worsened, and unchanged groups. Spearman rank correlation test was performed to determine the relationship between the PROMIS scores and reported disease status by patient/families.Results:More than 1,000 clinical visits from 184 patients were associated with self-reported PROMIS questionnaire entries in English. The median age at disease onset, diagnosis, and enrollment were 9.4 (IQR 7.5 – 11.3), 10.4 (IQR 8.4 -12.3), and 11.4 (IQR 9.5 – 13.8) years respectively. Seventy (38%) were males and 153 (83%) were White. All PROMIS scores correlated significantly (p<0.01) with patient reported variables and physician global assessment (PHGA). The correlation with function and PHGA was good (0.4-0.6) for Mobility, PB, and PI. All PROMIS scores, except physical activity, correlated significantly (p<0.05) with patient reported disease status. The correlation between patient-reported disease status and PHGA (0.75) was strong, moderate with Mobility (-0.53), PB (0.57), PI (0.5), and Fatigue (0.36), and weak with, SI (-0.23), UE (-0.23), and PA (-0.03). The changes of PROMIS scores over time for Mobility (p=0.015), PB (p<0.001), PA (p=0.019), and PI (p=0.011) compared to the self-reported status change (unchanged, improved, worsened) was significant. However, PROMIS score changes for Fatigue (p=0.055), SI (p=0.878), and UE (p=0.086) did not differ across various self-reported status change groups. After effective treatment when clinical disease activity score improved by at least 2.5 points (n=18), the change of PROMIS score from Mobility, PB, PI, UE was significant (p<0.05), whereas the change of PROMIS score from Fatigue, SI, and PA were not.Conclusion:PROMIS Questionnaires provide valuable information about disease status of children with CNO and correlate well with self-reported functional and other psychosocial domains. Mobility, PI, and PB show sensitivity to change after effective treatment or with disease status change. These instruments are useful for CNO clinical disease monitoring and research.REFERENCES:[1] Wu EY, Oliver M, Scheck J, et al. J Rheumatol. 2023 PMID: 37399459; PMCID: PMC10543471.Acknowledgements:The authors thank the CHOIR participants, research assistants and volunteers at all sites including Teresa Dickson, Corinne Lawler, Sumaya Aden, Thuan Bui, Kyra Shelton, Esha Mahal, Annie Xu, Kellen James, Shayla Nguyen, Zheng Xu, Ava Klein, Chessie Snider, Mabel Ho, Trang Pham, Anna Saack, Paige Trunnell, Emily Deng, Ana Park, Cailey Karshmer, Emma Leisinger, Mary Ellen Riordan, and Justine Griswold. We appreciate the help from Ingrid Goh, Mariana Correia Marques, and Min-Lee Chang for the testing of the registry database and the training material. In addition to the authors, the following CARRA CNO workgroup members participated in the February 2021 meeting: Ingrid Goh, Brian Nolan, Tzielan Lee, Annette Jansson, Aleksander Lenert, Lina Jaberi, David Cabral, Lauren Potts, Arielle Hay, Karine Toupin-April, Akaluck Thatayatikom, Ingram Chang, Piya Lahiry, Anja Schnabel, Mikhail Kostik, Nathan Rogers, Achille Marino, Dita Cebecauerova, Phillip Mease, Lindsey Bergstrom, Suzanne Li, Deborah McCurdy, Alex Theos, Matthew Hollander, Samira Nazzar, Farzana Nuruzzaman, Beverley Shea, and Chris Obrien. Statistical analysis was supported by CRMO Warriors Guild and Kaila’s Komfort generous donations.Disclosure of Interests:Yongdong Zhao Bristol-Myer Squibbs, Mary Eckert: None declared, Evelyn Yawei Wu I have worked as a paid consultant for 2 pharma companies – Enzyvant Therapeutics, Inc. and Pharming Healthcare, Inc., Melissa Oliver: None declared, Joshua Scheck: None declared, Sivia Lapidus: None declared, Ummusen Kaya Akca: None declared, Shima Yasin: None declared, Aleksander Lenert: None declared, Sara Stern: None declared, Antonella Insalaco: None declared, Manuela Pardeo: None declared, Gabriele Simonini: None declared, Edoardo Marrani: None declared, Xing Wang: None declared, Bin Huang: None declared, Leonard K Kovallick: None declared, Natalie Rosenwasser: None declared, Erin Balay: None declared, Gabriel Casselman: None declared, Adriel Liau: None declared, Ava Klein: None declared, Yurong Shao: None declared, Claire Yang: None declared, Molly Briggs: None declared, Ethan Mueller: None declared, Emily Deng: None declared, Paige Rhiannon Trunnell: None declared, Iris Hamilton: None declared, Elise Machrone: None declared, Doaa Mosad Mosa: None declared, Lori Tucker: None declared, Hermann Girschick: None declared, Ronald Laxer Akros Pharmaceutical, Eli Lilly Canada, Sanofi, Novartis, Sobi all less that 5000, Georgina Tiller: None declared, Jonathan Akikusa I have been on advisory boards in the last 12 months for Pfizer and Novartis with honoraria <$5000.I am an investigator in a drug trial for Abbvie., Christian Hedrich: None declared, Karen Onel: None declared, Fatma Dedeoglu: None declared, Marinka Twilt: None declared, Seza Ozen Novartis and SOBI and Bayer, Polly Ferguson I did provide consulting services last in 2020, Laura Schanberg: None declared, Bryce Reeve: None declared.

Background Juvenile Idiopathic Arthritis associated Uveitis (JIA-U) represents its most frequent extra-articular manifestation and the main cause of childhood uveitis in in developed countries. The broad variety of outcome measures utilized makes the comparison of the disease course, risk for complications, impairment in visual function, and responses to treatment quite difficult. Our aim was to summarize evidence regarding the current availability of outcome measures in JIA-U. Methods A systematic review between January 2000 and December 2018 was performed to identify studies investigating outcome measures used in JIA-U. Results The initial search identified 8254 articles of which 89 were potentially eligible. After the full text revision, a total of 27 studies, including 2 RCTs, were included. Among these studies 12 outcome measures for JIA-U use have been identified (grade of cells in the AC, grade of flare in the AC, VA, amblyopia, structural complications, use and sparing of oral corticosteroids and immunosuppressive drugs, surgery requirement, biomarkers, bilateral disease, JIA persistence, quality of life assessments, uveitis subtype). As regards primary outcome measures, 44% among studies included one or more variables related to disease activity (i.e. grade of flare, grade of cells); 56% included visual function performance (i.e. visual acuity); 68% (17/25) included one or more variables of disease-associated tissue damage or complications (i.e. cataract, amblyopia); 24% included disease features (i.e. bilateral disease; uveitis subtype); 44% included laboratory features (i.e. biomarkers); 8% included JIA features (i.e. persistence of disease); 12% included quality of life (i.e. EYE-Q); 44% included management (i.e. use and sparing of oral corticosteroids and other immunosuppressive drugs; surgery requirement). Conclusions Our systematic review surveys the heterogeneity around outcome measures related to JIA-U in children, even in RCTs. It does not provide the solution to overcome the heterogeneity in uveitis studies, but it does provide an estimate of the scale of the problems and provides data to inform this important debate; highlighting the requirement to obtain a new consensus regarding a common approach to identify suitable and efficient outcome measures in JIA-U.

Congenital heart block (CHB) is due to placental transfer of maternal anti-Ro/SSA autoantibodies to the fetus. The prevalence of CHB has been estimated as 1-2% in anti-Ro/SSA women while the recurrence rate is 16-19% (1). This condition is associated with a high rate of fetal/neonatal mortality and most of the cases requires pacemaker (PM) pacing. Given the rarity of CHB, limited data are available regarding the long-term follow-up of the offspring other than the cardiovascular complications. The results of the Italian Registry of the autoimmune congenital heart block were recently described (2). A peculiarity of this cohort was that most of the mothers had an established diagnosis of systemic autoimmune disease at CHB detection, in contrast with other registries where CHB was mostly incidentally detected in healthy women. Here we report an update, with the preliminary data regarding the long-term outcome of patients with CHB, their unaffected siblings and health controls born from mothers positive for Ro/SSA. Data regarding demography, treatment, maternal, neonatal outcome, and follow-up were collected through an online electronic datasheet. A dedicated questionnaire was created with the aim to investigate general health, cardiovascular follow-up, and frequency of autoimmune diseases. One-hundred and five cases of CHB in 99 patients were included from 1969 to December 2020. CHB was mostly detected in utero (97 cases, 92.3%) with 8 neonatal cases. Third degree CHB occurred in 71 cases (67.6%). Child mortality was observed in 29 (27.6%) cases: 20 in utero, 7 during neonatal period and 2 during childhood. Overall, a PM was implanted in 54 out of the 85 live births (63.5%). Then, our cohort was divided into 2 subgroups: pregnancy that occurred before (N=61) and after 2010 (N=44) with the aim to evaluate possible differences among the subgroups. Whereas mortality, PM, CHB degree were similar, CHB more frequently occurred in the last 10 years among Ro/SSA asymptomatic carriers than in the group of pregnancies before 2010 (53.6% vs 32.8%, p=0.038). Questionnaires from 14 surviving CHB cases, 8 unaffected siblings 12 controls born from mothers Ro/SSA positive were collected. Among CHB cases, 6 were males and 8 females, median age 12 years (range 6-28). All presented a third degree CHB, 10 required a neonatal PM pacing and one had an implantable ECG recorder. PM was substituted at least once in 9 patients, the oldest patient had to change it four times. No dilated cardiomyopathy occurred and most of the patients maintain an annual follow-up. Two cases of autoimmune diseases were registered among CHB cases, one idiopathic juvenile arthritis and one Cogan's vasculitis, both born from mothers with Sjogren Syndrome. Four cases of neurodevelopmental disorders occurred: three cases of learning disabilities (one in each group) and one case of speech disorder in the sibling group. In addition, a CHB case presented a stress disorder linked to frequent hospitalizations. This registry is an ongoing project aiming at collecting all Italian CHB. Moreover, here we reported the preliminary data concerning the evaluation of long-term follow-up of CHB patients. Our data, even if need to be confirmed in larger cohort, seems reassuring: no differences were reported comparing CHB patients with unaffected siblings or controls. [1]Brito-Zéron et al. Nat Rev Rheumatol 2015;11:301-312. [2]Fredi M et al. Front Cardiovasc Med. 2019 Feb 28;6:11. None declared