Background Non-infectious aortitis is often refractory to standard immunosuppressive therapy. IL-6 has been implicated in the pathogenesis of aortitis. Objectives Our aim was to assess the efficacy of the anti-IL6 receptor monoconal antibody tocilizumab (TCZ) in a series of patients with refractory non-infectious aortitis. Methods We reviewed 16 patients (14 women/2 men) with refractory aortitis diagnosed by imaging (CT angiography, MR angiography, and/or PET) that were treated with TCZ. Results The mean age ± SD was 51.4±20.1 years. The underlying conditions were: Takayasu arteritis (TakA) (N=7 cases), giant cell arteritis (GCA) (n=7), relapsing polychondritis (RP) (n=1), and aortitis associated with retroperitoneal fibrosis (n=1). TCZ was the first biologic drug used in all patients with GCA, and in the patient with aortitis associated with retroperitoneal fibrosis but in only 2 of 7 TakA patients. In the remaining cases anti-TNF inhibitors were prescribed before TCZ (standard dose was 8 mg/kg/iv/4 weeks). After a mean ± SD follow-up of 11.8±6.6 months most patients experienced clinical improvement, showing reduction of erythrocyte sedimentation rate from 43±36 mm/1st h to 5±4 mm/1st h at last visit. At TCZ onset, 25% of patients had fever and 19% polymyalgia rheumatica. These manifestations disappeared after 3 months of TCZ therapy. A corticosteroid sparing effect was also achieved (from 27.3±17.6 mg/day of prednisone at TCZ onset to 4.2±3.8 mg/day at last visit). TCZ had to be discontinued in a patient because of severe neutropenia. Conclusions TCZ appears to be effective and relatively safe in patients with inflammatory aortitis refractory to corticosteroids or to other biologic immunosuppressive drugs. Acknowledgements This study was supported by a grant from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2984

Background:Interstitial lung disease (ILD) is a severe complication of RA. Abatacept (ABA) have demonstrated efficacy in RA-ILD [1,2], although combined treatment with MTX or others DMARDs remain controversial.Objectives:To assess the efficacy and safety of ABA in monotherapy (ABAMONO) versus combined-ABA, ABA plus MTX(ABAMTX) or ABA plus other non-MTX DMARDs (ABANON-MTX), in RA-ILD.Methods:Observational multicenter study of RA-ILD caucasian patients treated with ABA. We analyzed in three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcomes: a) Dyspnea, b) FVC and DLCO, c) HRCT, d) DAS28-ESR, e) corticosteroid-sparing effect. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used between the three groups.Results:We studied 263 RA-ILD patients (mean age 64.6±10 years) [ABAMONO (n=111), ABAMTX (n=46) and ABANON-MTX (n=106)]. At baseline, ABAMONO patients were older (67±10 years) and took higher prednisone dose (10 [IQR 5-15] mg/day). There was no statistically significant differences in sex, seropositivity, ILD patterns, FVC, DLCO or disease duration. In all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnea, HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in corticosteroid-sparing effect in ABAMTX or ABANON-MTX(Figure 1). However, in the multivariable analysis, there were no differences in any outcome between the three groups(Table 1).Table 1.Effect in FVC, DLCO, dyspnea (mMRC) and HRCT pulmonary scan after abatacept.ABAMONON=111ABAMTXN=46ABANON-MTXN=106ABAMTXvs ABAMONOABANON-MTXvs ABAMONOpppp*UnadjustedAdjusted**UnadjustedAdjusted**Follow-up, median [IQR] months12 [6-36]12 [6-36]18[12-36]0.400.670.17Differences between basal and final follow-upFVC, %-0.5 (-2.5, 1.5)0.641.2(-0.6, 3.1)0.17-1.2 (-2.9, 0.5)0.170.330.300.390.590.90DLCO, %1.8 (-0.7, 4.34)0.160.5 (-3.8, 4.8)0.82-1.5 (-4.1, 1.1)0.260.200.580.800.070.32mMRC, n (%)Worsening5 (5)3 (8)5 (5)0.830.470.99Stable or improving93 (95)36 (92)87 (95)HRCT pulmonary scan, n (%)Worsening13 (28)2 (11)15 (25)0.240.100.78Stable or improving34 (72)19 (89)44 (75)DAS28-ESR-1.5 (-1.9, -1.0)0.000-1.2 (-1.8, -0.6)0.000-1.5 (-1.8, -1.2)0.0000.740.580.92Prednisone, mg/day-3.8 (-8.3, 0.8)0.10-2.7 (-4.6, -0.8)0.006-4.8 (-6.3, -3.4)0.0000.690.670.65Differences in DAS28-ESR, prednisone, FVC and DLCO are expressed as mean difference (95%CI) comparing final follow-up minus basal values.*Differences between the 3 groups.**Differences between ABAMTX vs. ABAMONO, and between ABANON-MTX vs ABAMONO are adjusted for age, disease duration until abatacept treatment, and DAS28 and prednisone dose at baseline.Abbreviations(DAS28-ESR: Disease activity score-erythrocyte sedimentation rate; DLCO: Carbon Monoxide Diffusing Capacity; HRCT: High resolution computed tomography; FVC: Forced vital capacity, mMRC: modified Medical Research Council scaleFigure 1.Conclusion:In caucasian individuals with RA-ILD, ABAMONO or ABAMTX or ABANON-MTX seems to be equally effective and safe. However, a corticosteroid-sparing effect is only observed in combined-ABA.References:[1]Fernández-Díaz C, et al. Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients. Semin Arthritis Rheum. 2018 Aug;48(1):22-27. doi: 10.1016/j.semarthrit.2017.12.012.[2]Fernández-Díaz C, et al. Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients. Rheumatology (Oxford). 2020 Dec 1;59(12):3906-3916. doi: 10.1093/rheumatology/keaa621.Acknowledgements:Spanish Collaborative Group of Interstitial Lung Disease Associated to Rheumatoid ArthritisDisclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Roche, bristol myers squibb, Belén Atienza-Mateo: None declared, Santos Castañeda: None declared, Rafael Melero: None declared, Francisco Ortiz-Sanjuán: None declared, Ivette Casafont-Solé: None declared, J. Loricera: None declared, Sebastián C Rodriguez-García: None declared, Iván Ferraz-Amaro: None declared, Miguel A González-Gay: None declared, Ricardo Blanco Speakers bureau: bristol myers squibb

Background Adult-onset Still’s disease (AOSD) is often refractory to standard immunosuppressive therapy. Tocilizumab (TCZ) has shown efficacy in isolated cases or in small series. Objectives We assess the efficacy of TCZ in AOSD. Methods Multicenter study of 27 patients with AOSD of 18 hospitals diagnosed according to Yamagouchi’s criteria (J Rheumatol 1992;19:424). TCZ was used due to lack of good response to standard therapy or to other biologic agents. Results The 27 patients (20 women/ 7 men), had a mean age of 37.2±15.9 (range 16-71) and an average duration of AOSD of 5.9±4.6 years (range 0.1-17) to onset of TCZ. Prior to the onset of TCZ and besides corticosteroids, patients had recived the following drugs: Metotrexate (26 patients), Anakinra (12), Etanercept (6), Adalimumab (5) and Infliximab (3). TCZ standard dose was 8 mg/k/iv/4 weeks. At TCZ onset, the most frequent clinical manifestations were joint (27 cases), cutaneous (14) and fever (18), along with analytical abnomalities, increase of ESR or CRP (20 cases), anemia (11) or leukocytosis (15). Clinical and analytical improvement was observed soon, 1st month after the onset of TCZ therapy (TABLE). After a mean follow-up of 20.8±12 months, cutaneous manifestations disappeared in 13 of 14 patients (92,9%), fever in 17 of 18 (94.4%) and joint manifestation in 22 of 27 (81,5%). Improvement of analytical abnormalities was observed in most cases with normalization of the blood cell count in 9 of 15 (60%) patients, anemia in 11 of 11 (100%), ESR in 15 of 19 (78.9 % ), CRP in 17 of 20 (85%), hepatic enzymes (AST/ALT) in 3 of 4 (50 %) and ferritin seric levels in 11 of 13 (84,6%). The median [IQR] dose of steroids was reduced from 15 [8.8-25] to 5 [1.3-7.5]. Conclusions In refractory AOSD, TCZ yields early and maintained clinical-analytical response, even in refractory cases to other biological agents. Although TCZ showed global efficacy, joint are more refractory than other systemic manifestations. Disclosure of Interest None Declared

BackgroundInterleukin (IL)-1 and IL-6 are pivotal cytokines in the pathogenesis of adult-onset Still's disease (AOSD).ObjectivesCompare the efficacy and safety of tocilizumab (TCZ) versus anakinra (ANK) given for at least 1 year to AODS patients refractory to conventional treatment.MethodsMulticenter study (31 hospitals) of 75 patients (TCZ; n=34 and ANK; n 41) with AODS refractory to conventional immunosuppressive drugs and in many cases also to other biological agents.ResultsComparisons of the group of patients with TCZ and ANK were: a) Average age: 39±16 vs. 34±14 years (p=0.2) b) Percentage of women: 76.5% vs. 63.4% (p=0.2) c) Median disease duration 4.2 [1-9] vs. 2.2 [0.3 to 4.9] years (p=0.14) d) Average dose of prednisone 15±9.9 mg/day vs. 28.3±22 mg/day (p=0.013) e) Median of conventional immunosuppressants (2 [1-3] vs 1 [1-2] (p=0.05) f) Median of other biological therapies: 1 [0-2] vs. 0 [0-1] (p=0.04). The initial dose of i.v. TCZ were: 8 mg/kg/4 weeks (n=22), 8 mg/kg/2 weeks (n=10) and 4 mg/kg/4 weeks (n=2). ANK dose was 100 mg/day s.c. Both biologic agents were often combined with a conventional immunosuppressive drug (55.9% vs 70.7%; p=0.2). Both biologic agents yielded a quick and sustained improvement of all clinical and laboratory parameters (Table). The improvement in the clinical parameters was similar in both groups. However an earlier improvement of CRP and ESR was observed following TCZ therapy. After a median follow-up of 19 months [12-31] with TCZ and 15.5 months [4.5 to 50] with ANK (p=0.1), the major adverse effects in the TCZ group were: elevation liver enzymes (n=4), mild to moderate leucopenia (4), upper respiratory tract infection (3), pneumonia (1), pyelonephritis and severe enterocolitis (1) and spondylodiscitis (1). In the group of ANK: skin lesions (n=8), mild leucopenia (3), myopathy (1), respiratory infection by P. aeruginosa and gluteal abscess (1), herpes zoster (1), osteomyelitis (1) and infection of urinary tract (2). While none of the TCZ-treated required discontinuation of the drug due to inefficacy, ANK had to be discontinued for this reason in 11 patients (p=0.001). Adverse effects leading to discontinuation of the drug were observed in 2 patients with TCZ and 4 patients with ANK (p=0.54).ConclusionsTCZ and ANK are associated with a rapid and sustained clinical improvement in most patients with refractory AODS. However, TCZ appears to be more effective than ANK.Disclosure of InterestNone declared

Background: Interstitial lung disease (ILD) associated with Rheumatoid Arthritis (RA) has a poor prognosis. Treatments such as anti-TNF, have been implicated in the exacerbation of an ILD. Objectives: Our objective is to evaluate and compare the evolution of ILD in patients with RA treated with Abatacept (ABA), Rituximab (RTX) and Tocilizumab (TCZ) after 1 year of treatment. Methods: Retrospective multicentre study of patients with ILD and AR treated with ABA, RTX and TCZ at standard doses. The ILD was diagnosed by CT. Conclusions: There seems to be a trend towards a better radiological response in patients treated with RTX and ABA. It would be necessary prospective studies. Background: Approximately a third of Rheumatoid Arthritis (RA) patients treated with tumour necrosis factor (TNF)-a inhibitors such as Infliximab (IFX) fail to respond. This has prompted a widespread interest in the finding of measures for predictors of response to TNFa inhibitors. Objectives: To search for serum autoantibodies that aid to identify RA patients most likely to benefit from IFX. Methods: We analysed serum of 170 biologic-naïve RA patients at baseline assigned to receive IFX plus methotrexate. The serum samples were distributed in 3 independent samples sets that were provided by 3 different sources: 1 discovery sample set (n=24) collected from Hospital Clínico Universitario of Santiago de Compostela (Spain) and 2 validation sample sets collected from Hospital Universitario de A Coruña (Spain), (n=61); and the Swedish Farmacotherapy (SWEFOT) trial (Sweden), (n=85). The European League Against Rheumatism (EULAR) criteria were used to assess the clinical response at six months of follow-up: good response (GR, n=60), moderate (MR, n=60) and non-response (NR, n=50). A suspension bead array platform built on protein fragments within Human Protein Atlas and selected from an initial screening using an array containing 42 000 antigens was employed to identify the IgG and IgA autoantibodies in the discovery sample set and validate the results within the 2 validation sets. Thresholds for autoantibodies were calculated by Receiver Operating Characteristics (ROC) curve analysis performed with SPSS 24. Results: Our data revealed a more prevalent IgG reactivity and higher IgG autoantibody levels against the antigen Centromere Protein F (CENPF) in GR when compared with NR, showing an overall reactivity of 31% vs 0%, 45% vs. 26% and 17% vs 4% in the three sample sets analysed respectively. The area under the ROC curve was 0,649 [p-value=0.049; IC 95% (0.510-0.789)]. CENP-F is a proliferation-associated and cell cycle-dependent centromere autoantigen that might be involved in the increased or abnormal cell proliferation that occurs during RA process. Interestingly, our results also showed that IgA autoantibodies levels toward the antigen Solute Carrier family 39 member 2 (SLC39A2), a zinc transporter protein, were decreased in GR when compared with MR in the discovery sample set and this trend was significantly validated (p=0.018) in the SWEFOT c...