Explore the vast range of titles available.

Objective To evaluate the genetic findings, demographic features and clinical presentation of tumour necrosis factor receptor-associated autoinflammatory syndrome (TRAPS) in patients from the Eurofever/EUROTRAPS international registry. Methods A web-based registry collected retrospective data on patients with TNFRSF1A sequence variants and inflammatory symptoms. Participating hospitals included paediatric rheumatology centres and adult centres with a specific interest in autoinflammatory diseases. Cases were independently validated by experts in the disease. Results Complete information on 158 validated patients was available. The most common TNFRSF1A variant was R92Q (34% of cases), followed by T50M (10%). Cysteine residues were disrupted in 27% of cases, accounting for 39% of sequence variants. A family history was present in 19% of patients with R92Q and 64% of those with other variants. The median age at which symptoms began was 4.3 years but 9.1% of patients presented after 30 years of age. Attacks were recurrent in 88% and the commonest features associated with the pathogenic variants were fever (88%), limb pain (85%), abdominal pain (74%), rash (63%) and eye manifestations (45%). Disease associated with R92Q presented slightly later at a median of 5.7 years with significantly less rash or eye signs and more headaches. Children were more likely than adults to present with lymphadenopathy, periorbital oedema and abdominal pains. AA amyloidosis has developed in 16 (10%) patients at a median age of 43 years. Conclusions In this, the largest reported case series to date, the genetic heterogeneity of TRAPS is accompanied by a variable phenotype at presentation. Patients had a median 70 symptomatic days a year, with fever, limb and abdominal pain and rash the commonest symptoms. Overall, there is little evidence of a significant effect of age or genotype on disease features at presentation.

BackgroundAdult-onset Still’s disease (AOSD) and Systemic Juvenile Idiopathic Arthritis (SJIA, formerly termed Still’s Disease), are rare polygenic autoinflammatory disorders of unknown etiology. The clinical course of AOSD/SJIA has been distinguished into different phenotypes, described on the basis of the evolution of symptoms over time. In a sizeable proportion of affected patients, disease remission can be achieved with treatments, that can be progressively tapered and stopped without relapse. Not much information is available on drug-free remission predictors.ObjectivesTo look for drug-free remission predictors in a retrospective monocentric cohort of AOSD/SIJA patients.MethodsRetrospective evaluation of AOSD/SIJA patients followed up in an Italian Rheumatology Unit between January 1997 and September 2022. All patients fulfilled the Yamaguchi criteria or PRINTO preliminary criteria. Drug-free remission was defined as the absence of clinical and laboratory markers of disease activity and absence of treatment for at least 6 months. Differences between patients who achieved drug-free remission or not were assessed using the using Mann-Whitney test, Student’s t-test, Chi-squared test and Fisher test when appropriate.Results57 AOSD and 7 SIJA consecutive patients were included in the study. Drug-free remission was achieved in 23 patients (35.9%) after a median period of 3,62 years (IQR 1,37 – 6). Their main baseline demographic and clinical features, as well as treatment received are summarized in Table 1. Patients in the drug-free remission group more often had white blood cells count >15.000/uL at baseline (p:0.004) than other patients. On the contrary, patients who failed drug-free remission more frequently were treated with Cyclosporine A (CyA) at disease onset (p:0.042). No significant difference was observed when analyzing if treatment with csDMARDs or bDMARDs was started within 3 months of the disease onset or not.ConclusionHyperleukocytosis at baseline was identified as a potential predictor of drug-free remission in our cohort of AOSD/SIJA patients, while this was more difficult to obtain in patients treated with CyA at the disease onset. Larger and collaborative studies are needed to confirm and better define these results.References[1]Yamaguchi M et al. J Rheumatol. 1992 Mar;19(3):424-30. PMID: 1578458.[2]Martini A et al. J Rheumatol. 2019 Feb;46(2):190-197.Table 1.Baseline demographic and clinical features and treatment at disease onset.Drug-free remissionn: 23No drug-free remissionn: 41p-valueAOSD n (%)20 (87.0%)37 (89.2%)0.69Male n (%)12 (52.2%)14 (34.2%)0.16Age at onset, years Mean±SD30.5 ±13.636.6 ±15.40.12Follow-up duration, years Median (IQR)6.5 (2.7–10.7)8.6 (3.5-15.3)0.94Ferritin mg/mL at onset, Median (IQR)1766 (682-11594)1255 (551-6620)0.61WBC >15000/uL at onset, n (%)15 (71.4%)13 (32.5%)0.0037WBC/uL at onset, Mean±SD17337 ±822314562 ±59950.14Hb g/dl at onset, Mean±SD10.9 ±1.811.3 ± 1.80.37PLTx103/uL at onset, Mean±SD325.30 ±171.97328.74 ±135.60.93CRP mg/L at onset, Mean±SD130.8 ±79.1143.2 ±108.60.65ALT U/L at onset, Median (IQR)68 (32-122)59 (25 -117)0.40AST U/L at onset, Median (IQR)44 (22-90)49 (27 -90)0.26Modified Pouchot’s score, Mean±SD6.1 ±1.466.6 ±1.730.24MAS at disease onset, n (%)2 (8.7%)5 (12,2%)1Treatment with csDMARDs (within 3 months since disease onset), n (%)9 (39.1%)23 (56.1%)0.3Treatment with cyclosporine (within 3 months since disease onset), n (%)08 (19.5%)0.04Treatment with b/tsDMARDS (within 3 months since disease onset), n (%)3 (75%)9 (34.6%)0.27Legend: WBC White Blood Cell; Hb Hemoglobin, PLT Platelets, CRP C-Reactive Protein, ALT Alanine Transaminase, AST Aspartate Transaminase, MAS Macrophage Activation Syndrome, csDMARDs conventional Disease-Modifying Antirheumatic Drugs, b/tsDMARDs biological/targeted synthetic Disease-Modifying Antirheumatic DrugsAcknowledgements:NIL.Disclosure of InterestsGiulia Fontana: None declared, Francesca Crisafulli: None declared, Micol Frassi Speakers bureau: Novartis, Lilly, marco Cattalini Consultant of: SOBI, Novartis, Franco Franceschini: None declared, Paolo Airò Speakers bureau: Bristol Myers Squibb, Bohringer Ingelheim, Consultant of: Bristol Myers Squibb, Bohringer Ingelheim,

Background:Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disease with remitting and recurring bone inflammation. There is no uniformly effective treatment. It is not known if CNO has an adverse effect on growth in pediatric population.Objectives:To obtain longitudinal data on growth in a large-scale multinational prospective cohort of pediatric CNO patients with data from EUROFEVER registry.Methods:Inclusion criteria were children with CNO with anthropometric data available during the first 2 years after diagnosis. Data was collected for demographics, treatment, potential vertebral fractures and growth, including serial heights, weights, and body mass index (BMI). Statistical analysis included descriptive statistic and Cox multivariate regression model.Results:A total of 237/573 (41.4%) children ≤ 18 years with CNO from the EUROFEVER registry met the inclusion criteria. The median [IQR] age at baseline (n= 237) was 10.07 years [7.94; 11.81] with median baseline height z-score of -0.08 [-0.72; 0.83] and median BMI z-score of 0.8 [-0.43; 2.1]. Longitudinal growth data was available for 125/237 (52.7%) patients, with median follow-up of 25.4 months [12.4; 44.1]. Treatment in this longitudinal cohort included NSAIDS (n=117, 93.6%), conventional synthetic DMARDS (n=38, 30.4%), biologic DMARDS (n=30, 24%), bisphosphonates (n=12, 9.6^0, and glucocorticoids (n=34, 27.2%). The median [IQR] duration of glucocorticoid treatment was 70 [30;168] days; the median prednisone equivalent dose was 0.55 [0.27;1.01] mg/kg/day. Active disease was present in 85.6% of patients during the final 3 months of follow-up. No spinal fractures were present at baseline nor at the final follow-up. There was no difference between baseline height and BMI between 125 patients with longitudinal data and 112 patients with baseline data only. In the longitudinal cohort, the median height z-scores at baseline and at final follow-up (-0.1 [-0.7; 0.8] vs. -0.02 [-0.78; 0.59]) were similar. Similarly, the median baseline and final follow-up BMI z-scores were not statistically different (0.83 [-0.27; 2.13]) vs. 0.79 [-0.08; 1.96]). However, growth failure, defined as height deflection (change in height z-score less than -0.25/year) was present in 24.8% of patients, with no gender difference, with no additional effect from corticosteroids.Conclusion:CNO had no significant impact on growth in affected children at baseline. Height deflection at final follow-up was present in 24.8 % of patients. No spinal fractures were present to account for poor linear growth. Our results suggest that recurring episodes of inflammation can adversely affect linear growth during the first 2 years after diagnosis.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Paivi Miettunen: None declared, Luca Carlini: None declared, Antonella Insalaco: None declared, Jordi Anton: None declared, Juergen Brunner: None declared, Elizabeth Legger: None declared, Marco Cattalini: None declared, Esther Hoppenreijs: None declared, Maria Alessio: None declared, Eugenia Mosci: None declared, 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, Marco Gattorno: None declared.

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.

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.

Background:The treatment for non-systemic Juvenile Idiopathic Arthritis (JIA) patients is guided by „treat to target“ principle with progressive intensification of treatment to reach optimal disease control. It is not known if patients’ adverse event (AE) profile worsens, as their treatment is intensified.Objectives:Our goal was to report AEs of at least moderate intensity, serious AE and events of special interest (ESI) in non-systemic-JIA patients as they progressed from less intensive treatment with non-steroidal anti-inflammatory drugs (NSAIDs) to treatment with conventional synthetic and biologic DMARDs (csDMARDs/bDMARDs) with data from Pharmachild registry.Methods:Inclusion criteria were children with non-systemic-JIA as per ILAR criteria with whole drug exposure from onset to last observation. Data was available from 1987 until December 2021. Non-systemic-JIA patients were classified according to their treatment (chosen by the treating physician) into either a “Control group” (CG) (NSAIDs±intra-articular (IA) glucocorticoids only) or a “STEP-up group” (starting with NSAIDS±IA glucocorticoids but subsequently requiring DMARDS as required for disease control): STEP-1 (NSAIDs±intra-articular glucocorticoids); STEP-2 (csDMARDs±oral glucocorticoids), and STEP-3 (bDMARDs±other medications). AEs were classified by the latest version of MedDRA dictionary (Version 23.1). Statistical analysis included descriptive statistics and Cox multivariate regression model.Results:A total of 8052 non-systemic JIA patients (69.9% female) were included: 719 (8.95%) in CG; 7333 (91.1%) in STEP-1; 6856 (85.1%) in STEP-2 and 5052 (62.7%) in STEP-3. The most frequent JIA category was oligoarthritis (76 % in CG versus 39.1% in STEP-1). The median (IQR) duration of each treatment period was 5.54 (2.88-9.18) years: CG 2.65 (1.04-6.38), STEP-1 0.62 (0.25-1.79), STEP-2 1.59 (0.57-3.85) and STEP-3 3.13 (1.48-5.58) years. Methotrexate (94%) and Etanercept (70%) were the most frequent conventional synthetic and biologic DMARDs, respectively. AEs were seen in all groups, least frequently in STEP-1 (1.8%) and most frequently in STEP-3 (24.4%). SAEs were most common in STEP-3 (492 (8%) patients), and rare in STEP-1 (62 (0.8%) patients) and CG (6 (0.8%) patients). Infections were the most frequent AEs in all groups (Incidence rates 0.33-4.14/100 patient years), with bDMARD group having the highest rate. Gastrointestinal disorders were most frequent in STEP-2 (N, IR, 95% CI: 330, 1.81 (1.62- 2.01)), all other AEs in STEP-3. Patients treated with bDMARDs had the highest risk for development of first episodes of AE, SAE, infection and serious infection, with highest hazard ratio for serious infection (HR, 95% CI) at 19.17 (9.74- 37.74).Conclusion:This is the first attempt to present a dynamic AE profile in a very large sample of non-systemic-JIA patients from an international pharmacovigilance registry applying a novel method of using patients as their “own controls”. Risk of AEs increased, and AE severity worsened with treatment intensification, with bDMARDs associated with a higher prevalence of AE, SAE and ESI when compared to treatment with csDMARDS or NSAIDs. The most frequent ESIs were infections.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Paivi Miettunen: None declared, Ana Rebollo Gimenez: None declared, Luca Carlini: None declared, Angela Pistorio: None declared, Violeta Panaviene: None declared, Jordi Anton: None declared, Sylvia Kamphuis: None declared, Troels Herlin: None declared, Pavla Dolezalova: None declared, Marco Cattalini: None declared, Gordana Susic: None declared, Helga Sanner: None declared, Maria Cristina Maggio: None declared, Soad Hashad: None declared, Reem Abdwani: None declared, Donato Rigante: None declared, Ana Rodriquez Lorzano: None declared, Chiara Pallotti: None declared, Joost F. Swart: None declared, Nicolino Ruperto Abbvie, Aclaris, Amgen, Astra Zeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lily, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi, Abbvie, Aclaris, Amgen, AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lily, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi.

BackgroundEvidence about the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious intermediate uveitis/pars planitis, posterior uveitis and panuveitis is still limited.ObjectivesAim of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis.MethodsThis is an international multicenter study based on real-life data from pediatric patients treated with ADA due to non-anterior uveitis. Data were drawn from the retrospective branch of the AutoInflammatory Disease Alliance (AIDA) registry dedicated to uveitis. Figure 1 provides the flow diagram describing the selection of the patients enrolled on October 1st, 2022.Results21 patients (36 affected eyes) were enrolled. Eleven patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a partial response with reduced frequency of relapses (3 cases), reduced severity of relapses (3 cases) or reduced frequency and severity of relapses (4 cases). The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (p=0.0009). Macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoids dosage significantly decreased at the last assessment (p=0.005). As observed in Table 1, intermediate uveitis/pars planitis (p=0.01) and posterior uveitis (p=0.03) were more frequent among patients with full response to ADA; panuveitis was significantly more frequent among patients continuing to experience uveitic flares (p=0.001). Regarding the safety profile, a case of generalized adenopathy was observed.ConclusionADA had a role in all pediatric patients with non-anterior uveitis with a significant glucocorticoid sparing effect. Panuveitis seems to be more frequent among patients continuing to experience uveitic flares.Figure 1.Study flow diagram illustrating the process leading to the selection of patients. Abbreviations: ADA, adalimumab; AIDA, AutoInflammatory Disease Alliance; NIU, non-infectious uveitis.Table 1.Baseline features of patients showing a full control of ocular relapses (group 1) and those experiencing ocular relapses despite the improvement in the frequency and/or the severity of ocular flares. Abbreviations: IBD: inflammatory bowel disease; IQR, interquartile range JIA: juvenile idiopathic arthritis; VKH: Vogt-Koyanagi-Harada syndrome; CS: corticosteroids.Group 1 – no further uveitis flaresGroup 2 – reduced frequency or severity of relapsesp valueN° patients/eyes11/1910/17Male/Female, N°6/57/30.96Mean age at uveitis onset, years (mean ± SD)10.8 ± 3.87.7 ± 3.60.08Unilateral/bilateral involvement at the onset3/82/50.83Mean duration from uveitis onset at ADA introduction, months – median (IQR)11 (24)12 (17)0.97Mean duration of follow-up, months – median (IQR)11 (15)27 (28.5)0.08Anatomical classification, N° eyes (%)Pars planitis, 10 (52.6)Posterior, 5 (26.3)Panuveitis, 5 (26.3)Pars planitis, 2 (11.8)Posterior, 0 (0)Panuveitis, 14 (82.4)0.010.030.001Uveitis presentation, N° eyes (%)Sudden, 9 (47.4)Insidious, 9 (47.4)Unknown, 1 (5.3)Sudden, 12 (70.6)Insidious, 5 (29.4)Unknown, 0 (0)0.160.28Uveitis course, N° eyes (%)Acute, 2 (10.5)Recurrent, 3 (15.8)Chronic, 12 (63.2)Unknown, 2 (10.5)Acute, 0 (0)Recurrent, 10 (58.8)Chronic, 7 (41.2)Unknown, 0 (0)0.180.0080.19Concomitant systemic diseases, N° eyes (%)Idiopathic, 7 (63.6)Behçet’s disease, 2 (18.2)IBD, 1 (9.1)Scleroderma, 1 (9.1)Idiopathic, 6 (60)JIA, 2 (20)VKH syndrome, 1 (10)Behçet’s disease, 1 (10)0.92ADA molecule used, N° eyesOriginator, 5 (45.5)ABP501, 3 (27.3)SB5, 2 (18.2)GP2017, 1 (9.1)Originator, 6 (60%)ABP501, 2 (20)SB5, 1 (10)GP2017, 1 (10)0.52Concomitant CS treatment at the start of ADA, N° patients (%)8 (73.7)6 (60)0.55Concomitant cDMARDs at the start of ADA, N° patients (%)7 (63.6)9 (90)0.17REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundTumor necrosis factor receptor-1 associated periodic syndrome (TRAPS) is a periodic fever syndrome, whose main symptoms are rashes, musculoskeletal and abdominal pain, and periorbital edema. Although TNF inhibitors have been shown to be effective in some patients, their efficacy tends to decrease over time.1-4 Anti-IL-1 treatments have also been used in an effort to provide long term control of the inflammatory manifestations.ObjectivesThe proof of concept study was designed to assess safety, efficacy, and pharmacokinetics (PK) /pharmacodynamic (PD) data upon canakinumab (CAN) and to determine the appropriate dosing for further development of CAN treatment in patients with TRAPS.MethodsThis was an open-label, single treatment arm, efficacy and safety study of monthly CAN 150 mg (2 mg/kg for patient ≤40 kg) SC in patients with active recurrent or chronic TRAPS. Patients were treated for 4-months with a maximum 5-month follow-up period. The initial follow-up period was followed by a maximum 24-month long-term treatment period. The primary efficacy outcome was induction of complete or almost complete response in active TRAPS patients at Day 15 after first CAN dosing.ResultsA total of 20 patients were exposed to study medication, out of which 18 (90%) patients completed the study. Primary endpoint showed that 18 patients [90%; 95% CI: 75.1, 99.9] achieved a complete or almost complete response at Day 15, while 20 (100%) and 12 (60%) patients had clinical and serological remission, respectively (Table). Already at Day 8, 16 patients (80%) achieved a complete or almost complete response, while 18 (90%) and 7 (35%) patients had clinical and serological remission, respectively. A total of 60% of patients experienced study drug-related AEs, most commonly upper respiratory tract infections. Seven patients (35%) experienced SAEs, none of which were related to study drug. Furthermore, there were no deaths during the study.ConclusionsCanakinumab was effective in rapidly alleviating clinical signs and symptoms of TRAPS, whilst normalizing serological inflammatory markers and providing sustained disease control. The safety profile was consistent with previous canakinumab studies in other indications. These data support the ongoing development of canakinumab in this therapeutic area.ReferencesSimon A, et al. Am.J.Med 2004;117:208-10.Weyhreter H, et al. J Pediatr 2003;142:191-3.Jacobelli S, et al. Rheumatology (Oxford) 2007;46(7):1211-2.Arostegui JI, et al. Eur.J.Pediatr 2005;164:13-6.Disclosure of InterestH. Lachmann Grant/research support from: Novartis, Consultant for: Novartis, M. Cattalini Consultant for: Novartis, SOBI, Speakers bureau: Novartis, L. Obici Consultant for: Novartis, Speakers bureau: Novartis, R. Barcellona: None declared, A. Speziale Employee of: Novartis, Y. Joubert Employee of: Novartis, G. Junge Employee of: Novartis, M. Gattorno Grant/research support from: Novartis, SOBI, Speakers bureau: Novartis, SOBI

Aicardi-Goutières syndrome (AGS) is a rare genetic encephalopathy characterized by neurological and extraneurological involvement. A clinical overlap between AGS and systemic lupus erythematosus (SLE) has been reported. We describe an AGS patient who developed autoimmune manifestations: thyroiditis, cANCA positivity, antiphospholipid antibodies and cerebral ischemia. This first description of antiphospholipid syndrome in a TREX1-mutated patient further expands the clinical spectrum of AGS. Although the clinical overlap with SLE may indicate common pathogenic mechanisms, the autoimmune manifestations in AGS are so extensive that we suggest they should be considered a clinical feature of the disease, rather than a sign of coexistent SLE.

BackgroundChronic nonbacterial osteomyelitis (CNO) is a rare inflammatory disorder that primarily affects children. Its hallmark is recurring episodes of sterile osteomyelitis. The clinical presentation is insidious onset of bone pain with or without fever. Pathogenesis is still unknown.ObjectivesWe conducted a retrospective review to assess the clinical characteristics and treatment responses of a cohort of pediatric CNO patients.MethodsChildren diagnosed with CNO at 8 tertiary care centers in Italy between 2004 and 2014 were identified. Clinical, laboratory, radiological and histological data were obtained.ResultsForty-seven patients with CNO (33 females, 14 males) were identified. The average follow up was 34 months (range 2 – 144 months). Bone pain was the leading symptom; median age of first complaint was 9 years (range 4-14 ys). A total of 210 localizations were found with a median of 4 localizations for patient. The majority of bone lesions were located in the metaphyses of the long bones (38%), vertebral column (35%), pelvis (12%) and clavicle (8%). Six patients had only one localization and 3 of them had the clavicle involvement. Sixteen out of 47 patients (34%) presented extra-articular symptoms: fever (13), psoriasis (5, one of them had acrodermatitis continua of Hallopeau), proteinuria (4), growth failure (2), acne (2), pustolosis (2), acrocyanosis (1). One out of 4 patients with proteinuria underwent renal biopsy that showed a mesangial glomerulonephritis. One other patient presented a steroid-dependent nephrotic syndrome before the onset of bone symptoms; renal biopsy showed a minimal change glomerulonephritis disease. At onset blood examination revealed pronounced increased eritrosedimentation rate (ESR) and C-reactive protein (CRP) in 18 cases (38%); slight increased ESR and CRP in 7 cases (15%). In 35/47 (74%) patients diagnosis was formalized after biopsy. In the remaining patients diagnosis seemed clear for multifocal pattern, the peculiar localizations and/or the typical MRI images. NSAIDs were the first line therapy in all patients, with achievement clinical remission in 12/47 (25%). Corticosteroids were used in 24/47 patients with good response only in 12% of them. Among the other patients we chose bisphosphonate with good percentage of clinical remission (18/26, 70%).ConclusionsIn a Italian cohort of 47 children with CNO, skin and renal involvement were detected. Bisphosphonates were more likely to lead to clinical remission than NSAIDs and corticosteroids. So we think that CNO patients need a strict renal function control and bisphosphonates should be the first choice second-line treatment.Disclosure of InterestNone declared