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The N-glycosylation of human immunoglobulins, especially IgGs, plays a critical role in determining affinity of IgGs towards their effector (pro- and anti-inflammatory) receptors. However, it is still not clear whether altered glycosylation is involved in only antibody-dependent disorders like seropositive rheumatoid arthritis (RA) or also in pathologies with similar clinical manifestations, but no specific autoantibodies like seronegative RA. The clarification of that uncertainty was the aim of the current study. Another study aim was the detection of specific glycan forms responsible for altered exposure of native glycoepitopes. We studied sera from seropositive RA (n = 15) and seronegative RA (n = 12) patients for exposure of glycans in native IgG molecules, followed by determination of specific glycans by capillary electrophoresis with laser-induced fluorescent detection (CE-LIF). Aged-matched groups of normal healthy donors (NHD) and samples of intravenous immunoglobulin IgG preparations (IVIG) served as controls. There was significantly stronger binding of Lens culinaris agglutinin (LCA) and Aleuria aurantia lectin (AAL) lectins towards IgG from seropositive RA compared to seronegative RA or NHD. CE-LIF analysis revealed statistically significant increases in bisecting glycans FA2BG2 (p = .006) and FABG2S1 (p = .005) seropositive RA, accompanied by decrease of bisecting monogalactosylated glycan FA2(6)G1 (p = .074) and non-bisecting monosialylated glycan FA2(3)G1S1 (p = .055). The results suggest that seropositive RA is distinct from seronegative RA in terms of IgG glycan moieties, attributable to specific immunoglobulin molecules present in seropositive disease. These glycans were determined to be bisecting GlcNAc-bearing forms FA2BG2 and FABG2S1, and their appearance increased the availability of LCA and AAL lectin-binding sites in native IgG glycoepitopes.

Background:Due to better treatment strategies and higher remission rates the management of rheumatoid arthritis (RA) patients in sustained remission is of increasing interest (1). The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated the possibility to taper and stop disease modifying anti-rheumatic drugs (DMARDs).Objectives:To compare one-year remission and relapse rates in rheumatoid arthritis patients randomized to continued treatment, reduced treatment or gradual treatment withdrawal after stable remission under routine care.Methods:Primary data of the phase III, randomized, controlled RETRO trial in RA patients with stable conventional synthetic and/or biologic DMARD treatment in sustained (>6 months) DAS28-ESR remission (Results:316 RA patients in sustained remission were included, 303 were randomized (CONT: N=100; TAP: N=102; STOP: N=101) and 282 (93%) had complete data sets after 1 year (CONT:N=93; TAP: N=93; STOP: N=96; Table 1). After 1 year, 81.2%, 58.6%, 43.3% of patients, maintained their remission state over 1 year in the CONT, TAP and STOP arms, respectively (p=0.0004 with log rank test for trend; Figure 1). Hazard ratios for flare were 3.02 (95%CI 1.69 to 5.40) and 4.34 (95%CI 2.48 to 7.60) for the TAP and STOP arms. RA patients who flared were more likely to be female, have longer disease duration, RF/ACPA positivity and higher baseline DAS-28 scores with standardized mean differences >0.2. Serious adverse events were reported in 10.8%, 7.5%, and 13.5% in the CONT, TAP and STOP arms, respectively.Table 1.Baseline CharacteristicsGroupControlReduceReduce/StopOverallN939396282Age, mean(SD)55.9 (12.7)56.9 (13.0)56.5 (13.3)56.5 (13.0)Female, n (%)53 (57.0)57 (62.0)57 (59.4)167 (59.4)RF, n (%)52 (55.9)58 (62.4)52 (54.2)162 (57.4)ACPA, n (%)53 (57.0)50 (54.9)55 (57.3)158 (56.4)Disease duration, years, mean(SD)7.6 (6.9)7.8 (6.9)6.8 (8.1)7.4 (7.3)Remission duration, months, mean(SD)20.6 (18.0)16.5 (15.9)22.7 (30.4)20.0 (22.6)Biologics, n (%)39 (41.9)44 (47.3)39 (40.6)122 (43.3)Methotrexate, n (%)71 (76.3)67 (72.0)75 (78.1)213 (75.5)Other DMARDs, n (%)24 (25.8)20 (21.5)16 (16.7)60 (21.3)Glucocorticoids, n (%)27 (29.0)23 (24.7)17 (17.7)67 (23.8)CRP, mg/L, mean(SD)0.3 (0.3)0.5 (0.5)0.5 (0.6)0.4 (0.5)ESR, mm/h, mean(SD)11.3 (8.4)12.2 (8.8)13.0 (10.0)12.2 (9.1)Tender joint count, mean(SD)0.2 (0.6)0.0 (0.2)0.1 (0.3)0.1 (0.4)Swollen joint count, mean(SD)0.1 (0.3)0.1 (0.3)0.1 (0.4)0.1 (0.3)Physician VAS,mm, mean(SD)1.8 (4.2)2.6 (4.4)2.0 (3.9)2.1 (4.2)Patient VAS,mm, mean(SD)6.4 (9.0)5.5 (8.3)4.5 (8.4)5.5 (8.6)HAQ, standard, mean(SD)0.2 (0.4)0.2 (0.3)0.2 (0.4)0.2 (0.4)HAQ, alternative, mean(SD)0.2 (0.4)0.1 (0.3)0.2 (0.3)0.2 (0.3)DAS-28, mean(SD)1.7 (0.7)1.7 (0.6)1.7 (0.6)1.7 (0.6)SDAI, mean(SD)1.4 (1.5)1.4 (1.5)1.3 (1.3)1.3 (1.4)DAS-28 remission, n (%)91 (97.8)93 (100.0)95 (99.0)279 (98.9)SDAI remission, n (%)79 (87.8)79 (84.9)88 (92.6)246 (88.5)Boolean remission, n (%)69 (75.8)71 (76.3)76 (79.2)216 (77.1)Conclusion:This randomized controlled study shows that half of RA patients in sustained remission relapse when tapering/stopping their DMARDs. Presence of autoantibodies, higher baseline DAS28-ESR and female sex are predictors for flares.References:[1]Schett G et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis. 2016 Aug;75(8):1428-37.Disclosure of Interests:Melanie Hagen Speakers bureau: advisory boards, Koray Tascilar Speakers bureau: advisory board, Michaela Reiser: None declared, Larissa Valor: None declared, Judith Haschka Speakers bureau: advisory board, Arnd Kleyer Speakers bureau: advisory board, Axel Hueber Speakers bureau: advisory boards, Bernhard Manger Speakers bureau: advisory boards, Jayme Cobra Speakers bureau: advisory boards, Camille Figuereido Speakers bureau: advisory boards, Stephanie Finzel Speakers bureau: advisory boards, Hans-Peter Tony Speakers bureau: advisory boards, Joerg Wendler Speakers bureau: advisory boards, Stefan Kleinert Speakers bureau: advisory boards, Florian Schuch Speakers bureau: advisory boards, Monika Ronneberger: None declared, Martin Feuchtenberger Speakers bureau: advisory boards, Martin Fleck Speakers bureau: advisory boards, Karin Manger: None declared, Wolfgang Ochs: None declared, Matthias Schmitt-Haendle: None declared, Hanns-Martin Lorenz Speakers bureau: advisory boards, Rieke Alten Speakers bureau: advisory boards, Jörg Henes Speakers bureau: advisory boards, Klaus Krueger Speakers bureau: advisory boards, Jürgen Rech Speakers bureau: advisory boards, Georg Schett Speakers bureau: advisory boards.

Background:Rheumatoid Arthritis (RA) is preceded by a clinically silent pre-phase characterized by autoimmunity against anti-modified protein antibodies including anti-citrullinated protein antibodies (ACPA). At this pre-stage patients already experience significant loss of volumetric peripheral bone mineral density (vBMD) compared to healthy controls measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) (1-2). However, the longitudinal course of vBMD changes during the preclinical phase, after diagnosis, and its association with time to disease onset have not been investigated.Objectives:To longitudinally characterize the changes of metacarpal and radial vBMD before and after the clinical onset of RA and its association with time to onset of arthritis.Methods:To explore the development of arthritis, we initiated a RA-at-risk cohort in 2011. (Ethics 334_16B). This prospective cohort includes adults positive for CCP-AB with or without musculoskeletal symptoms, excluding arthritis. Participants are regularly followed with clinical examination and HR-pQCT imaging of the MCP and radial bone to monitor early bone changes. HR-pQCT images with low motion grade artefacts were analyzed to obtain the total (D100), cortical (DComp) and trabecular (DTrab) vBMD (D100) in mg HA cm3.We descriptively analyzed the vBMD time course in patients who developed RA by fitting regression curves separately for the pre-clinical and clinical periods and estimated time-conditional marginal mean VBMDs for the 5-year peri-RA period. We analyzed time to diagnosis of clinical RA defined by the 2010 ACR/EULAR classification criteria using Cox regression models. Hazard ratios indicate the relative risk of clinical disease onset associated with 1 standard deviation reduction in bone density.Results:130 subjects (mean [SD] age 47.0 [12.2], 89 female [68%]) between 2011 and 2020 were analyzed. Median (IQR) follow-up duration for the cohort was 18.6 (4.6-47.6) months. Participants underwent 233 HR-pQCT scans and 58 (45%) underwent 2 to 6 scans with a median interval of 16.2 (12.2-21.2) months. 49 (38%) patients who developed RA had a pre-diagnosis follow-up of 4.1 (2.5-13.4) months and post-diagnosis follow-up of 22.0 (8.8-38.9) months. The time course of scaled bone mineral densities depicted in Figure 1A suggest that bone density around the MCP joints deteriorate in the preclinical phase of RA, which is mostly prominent in the trabecular bone. Modelling (Figure 1B) suggests that trabecular bone loss around the MCP joints has a constant pace regardless of the clinical status. Whereas the radial bone densities are relatively stable in the preclinical phase and show a reduction after the clinical onset of RA. Age and sex adjusted hazard ratios (95%CI) for the risk of RA clinical onset were 1.52 (1.03 to 2.25) for radius D100 and 1.66 (1.07 to 2.55) for radius DComp (Table-1).Table 1.Relative risk of RA development in the total cohort; crude and age/sex adjusted hazard ratios for one standard-deviation reduction in vBMD.CrudeAdjustedHR (95%CI)PHR (95%CI)PMCP.D-Comp1.16 (0.86 to 1.57)0.3361.20 (0.89 to 1.63)0.229MCP.D-Trab1.14 (0.83 to 1.57)0.4051.17 (0.85 to 1.62)0.341MCP.D1001.16 (0.83 to 1.61)0.3921.21 (0.86 to 1.71)0.265Rad.D-Comp1.42 (0.97 to 2.07)0.0711.66 (1.07 to 2.55)0.023Rad.D-Trab1.20 (0.87 to 1.66)0.2571.23 (0.88 to 1.71)0.223Rad.D1001.43 (0.99 to 2.06)0.0561.52 (1.03 to 2.25)0.033Conclusion:Metacarpal bone showed a constant decline that started already in the pre-phase of RA and continued after its clinical onset. In contrast, bone loss in the radius was not observed in the pre-phase but started at onset of RA. Low radial vBMD in the pre-clinical phase, however, was associated with a higher risk of RA onset. These findings suggest different spatiotemporal dynamics of bone loss before and after RA onsetReferences:[1]Kleyer A. et. al. Ann Rheum Dis. 2014, 73:854-60[2]Simon D. et. al. Ann Rheum Dis. 2020, doi:10.1002/art.41229Disclosure of Interests:None declared

Innate lymphoid cells (ILC) have a high potency for cytokine production independent of specific Ag stimulation. Imbalance of ILC subsets may influence cytokine production in humans and hence be associated with the development of inflammatory disease. Evidence for an imbalance of ILC homeostasis in human disease, however, is very limited to date. In this study we show that psoriatic arthritis (PsA), a severe disease of the joints depending on the activation of the IL-23/IL-17 pathway, is characterized by a skewed ILC homeostasis. Circulating ILC3s as potent source of IL-17/IL-22 were elevated in active PsA, whereas ILC2s, which produce proresolving cytokines, were decreased. The ILC2/ILC3 ratio was significantly correlated with clinical disease activity scores and the presence of imaging signs of joint inflammation and bone damage. Multivariable analysis showed that a high ILC2/ILC3 ratio is associated with remission in PsA, suggesting that specific alterations of ILC homeostasis control disease activity in PsA.

Adult onset Still's disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD.We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD.We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (pOur results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients.

Objective: To characterize the specific structural properties of the erosion-prone bare area of the human joint and to search for early microstructural changes in this region during rheumatoid arthritis Methods: An initial cadaveric study was used for exact localization of the bare area of the metacarpal heads, detection of cortical micro-channels (CoMiCs) in this region by high-resolution peripheral computed tomography (HR-pQCT) and, after anatomical dissection, their validation by micro-computed tomography (μCT). In the second part, number and distribution of CoMiCs were analyzed in 105 healthy individuals and 107 RA patients with similar sex and age distribution. Results: HR-pQCT investigation combined with adaptive thresholding allowed detection of CoMiCs in the bare area of cadaveric joints. Their existence in the bare area was additionally validated by μCT. In healthy individuals, the number of CoMiCs increased with age. RA patients showed significantly (p

Background:We have previously observed in RA patients that central nervous system (CNS) response to compression of a painful joint, measured using functional MRI (fMRI) of the brain as the number of blood oxygen level dependent (BOLD) signal positive voxels, is rapidly ameliorated, much earlier than any clinical response with anti-TNF treatment and a high baseline CNS pain response could predict better response to certolizumab pegol (CZP) treatment. Pre-CePRA was designed and conducted to test this effect in a randomized, placebo controlled trial of CZP and showed an incremental linear trend of DAS28 low disease activity (LDA) across study groups treated with placebo, and two CZP arms stratified as low or high pre-treatment CNS pain response.Objectives:To explore and describe pre-treatment CNS pain response associations with post treatment course of RA disease activity components and patient-physician discrepancy in global disease assessment.Methods:Patients fulfilling the 2010 ACR/EULAR classification criteria with moderate-severe disease activity (DAS-28>3.2) under stable DMARD treatment were recruited. Patients underwent an fMRI scan, stratified by a whole-brain BOLD positive voxel count threshold of 700 units and randomized to treatment with CZP or placebo in a 2:1 ratio. We descriptively assessed components of RA disease activity (Table 1 + 2). We summarized the mean results and 95% confidence intervals of these measurements at study timepoints and compared the 3 study groups at week 12 using one-way ANOVA and post-hoc Tukey tests.Results:156 eligible patients were screened and 139 (99 females, 71%) patients with moderate-high disease activity were randomized. ANOVA and pairwise comparisons showed that PGA-VAS improvement was larger in the CZP-H group whereas more similar to that in placebo in the CZP-L group. PhysGA-VAS however was similarly reduced in both CZP groups. Patients in the CZP-L group constantly rated their pain numerically higher than physicians whereas in the CZP-H group an initially higher discrepancy numerically reduced over time.Conclusion:These results suggest that improved patient global disease activity assessment could be the main driver of improved DAS-28 LDA rates with CZP treatment in patients with a high CNS pain response. Our findings indicate a potential role of fMRI imaging of the brain to further understand disease activity perception in RA patients.Figure 1.Course of disease activity components through trial timepoints. *indicates log-transformed y axis. *#x002A; Discrepancy equals Patient global minus physician global assessment.Disclosure of Interests:Hannah Schenker: None declared, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Koray Tascilar: None declared, Melanie Hagen: None declared, Verena Schönau: None declared, Marina Sergeeva: None declared, Mageshwar Selvakumar: None declared, Laura Konerth: None declared, Jutta Prade: None declared, Sandra Strobelt: None declared, Larissa Valor: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Frank Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Janssen, Consultant of: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Speakers bureau: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Christoph Baerwald Consultant of: CGB received speaker or consulting fees from AbbVie, Paid instructor for: CGB received speaker or consulting fees from AbbVie, Speakers bureau: CGB received speaker or consulting fees from AbbVie, Stephanie Finzel: None declared, Reinhard Voll: None declared, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Arnd Doerfler: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Andreas Hess: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Background:Tumor necrosis factor inhibitors have revolutionized the treatment of rheumatoid arthritis (RA). However, only about 50% of the patients respond well to TNF inhibitors. Therefore, markers that predict response to TNF inhibitors are valuable. Previously we demonstrated that central nervous system (CNS) response to nociceptive stimuli, measured by fMRI of the brain as blood oxygen level dependent (BOLD) signals, decreases already after 24 hours of anti-TNF administration a higher pre-treatment BOLD signal volume seems to predict clinical response to treatment with certolizumabpegol (CZP)1,2. We therefore hypothesized that the baseline volume of BOLD signal in the CNS could predict anti-TNF treatment response.Objectives:To perform a randomized placebo controlled trial in active RA patients to test the effect of TNF inhibition on arthritis induced pain activity in the brain and to test whether patients with high-level RA-related brain activation react differently to TNF-inhibitors than patients with low-level brain activation.Methods:Adult RA patients fulfilling the 2010 ACR/EULAR classification criteria with a DAS28>3.2 receiving stable DMARD treatment for at least 3 months were eligible. Patients underwent the first fMRI at screening measuring BOLD signal upon MCP joint compression and were stratified into low (< 700 units) and high (>700 units) voxel counts. Then patients were randomized to CZP or placebo with a 2:1 ratio. The second and third fMRI were performed after 12 and 24 weeks, respectively. Control stimulation was done by measuring brain activation after non-painful finger tapping.Results:156 RA patients with moderate-to-high disease activity participated in the study. In the finger tapping control, fMRI showed no significant changes in BOLD signal in the CZP-L and CZP-H arms, but a slight but significant decrease (p=0.043) was observed. After joint compression, the CZP-L group showed significant increase in the BOLD signal volume (p=0.043) in fMRI-2 as compared to fMRI-1 with no further significant changes. In contrast, in the CZP-H group, the BOLD signal volume significantly decreased (p=0.037) in fMRI-2 and continued to decrease further, p=0.007. No significant changes were observed in the placebo arm over time.Conclusion:TNF inhibition improves arthritis-related brain activity in the subgroup of RA patients with high baseline BOLD activity in the fMRI.References:[1]Hess, A.et al.PNAS (2011).[2]Rech, J. et al. Arthritis & Rheumatism (2013).Fig 1.BOLD fMRI responses to painful stimulationAcknowledgments:The study was supported by an unrestricted grant of UCB Biopharma SPRL Brussels, BelgiumDisclosure of Interests:Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Koray Tascilar: None declared, Hannah Schenker: None declared, Melanie Hagen: None declared, Marina Sergeeva: None declared, Mageshwar Selvakumar: None declared, Laura Konerth: None declared, Jutta Prade: None declared, Sandra Strobelt: None declared, Verena Schönau: None declared, Larissa Valor: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis, Abbvie, Speakers bureau: Novartis, Lilly, Frank Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Janssen, Consultant of: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Speakers bureau: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Christoph Baerwald Consultant of: CGB received speaker or consulting fees from AbbVie, Paid instructor for: CGB received speaker or consulting fees from AbbVie, Speakers bureau: CGB received speaker or consulting fees from AbbVie, Stephanie Finzel: None declared, Reinhard Voll: None declared, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Arnd Doerfler: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Andreas Hess: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Background:Psoriasis (PsO) and psoriatic arthritis (PsA) are two types of chronic inflammatory diseases that share a similar cytokines profile. About 30% of PsO patients also develop a joint involvement, but the underlying mechanism is still unclear. Innate lymphoid cells (ILC) and specifically the type 3 ILCs (ILC3s) have raised increasing interest as possible player in the pathogenesis of both diseases, as they produce the pathological key cytokine IL-17A.Objectives:We addressed the contribution of ILC3s to the pathogenesis of PsO and PsA in patients as well as murinein vivomodels.Methods:130 patients satisfying the Classification Criteria for Psoriatic Arthritis (CASPAR), 40 patients with PsO and 35 healthy volunteers were enrolled in the study. Information regarding clinical features, laboratory parameters were collected and psoriasis area severity index (PASI), disease activity score 28 (DAS28), disease activity in psoriatic arthritis (DAPSA), minimal disease activity score (MDA) were calculated. Magnetic resonance imaging (MRI) and high-resolution peripheral CT (HR-pQCT) were taken and PsA MRI score (PsAMRIS) was assessed. Flow cytometric analysis was performed and IFNγ-producing ILC1s, IL-4/IL-5-producing ILC2s and IL-17/IL-22-producing ILC3s were identified among ILCs. Multivariate linear regression and Receiver-Operating Characteristic (ROC) Curve analysis was performed using the IBM SPSS Statistics software. Different in vivo models were used to assess functional implications of ILCs at different time points of the disease. Joint inflammation was assessed through MRI and H&E staining of ankle areas. Peripheral blood was obtained from mice of each group and flow cytometry analysis was performed. High dimensional analyses including RNA-seq was performed to identify phenotypic characteristics of ILCs implemented into the pathogenesis of the disease.Results:Total number of circulating ILCs were increased in PsA patients compared to PsO and healthy controls (pConclusion:ILC3s not only correlate with various facets of PsA manifestations but also functionally contribute to synovitis and enthesitis suggesting them as interesting target for upcoming treatment strategies in the near future.Disclosure of Interests:Maria Gabriella Raimondo Grant/research support from: Celgene, Partner Fellowship, Simon Rauber: None declared, Markus Luber: None declared, Aleix Rius Rigau: None declared, Stefanie Weber: None declared, Charles Gwellem Anchang: None declared, Rahul Agarwal: None declared, Alina Soare: None declared, Michael Sticherling Grant/research support from: Novartis, Consultant of: Advisory boards Abbvie, Celgene, Janssen Cilag, Lilly, Pfizer, MSD, Novartis, Amgen, Leo, Sanofi, UCB, Speakers bureau: Abbvie, Celgene, Janssen Cilag, Leo, MSD, Novartis, Pfizer, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Andreas Ramming Grant/research support from: Pfizer, Novartis, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Speakers bureau: Boehringer Ingelheim, Roche, Janssen

Supplemental digital content is available in the text., Background Using a machine learning approach, the study investigated if specific baseline characteristics could predict which psoriatic arthritis (PsA) patients may gain additional benefit from a starting dose of secukinumab 300 mg over 150 mg. We also report results from individual patient efficacy meta-analysis (IPEM) in 2049 PsA patients from the FUTURE 2 to 5 studies to evaluate the efficacy of secukinumab 300 mg, 150 mg with and without loading regimen versus placebo at week 16 on achievement of several clinically relevant difficult-to-achieve (higher hurdle) endpoints. Methods Machine learning employed Bayesian elastic net to analyze baseline data of 2148 PsA patients investigating 275 predictors. For IPEM, results were presented as difference in response rates versus placebo at week 16. Results Machine learning showed secukinumab 300 mg has additional benefits in patients who are anti–tumor necrosis factor–naive, treated with 1 prior anti–tumor necrosis factor agent, not receiving methotrexate, with enthesitis at baseline, and with shorter PsA disease duration. For IPEM, at week 16, all secukinumab doses had greater treatment effect (%) versus placebo for higher hurdle endpoints in the overall population and in all subgroups; 300-mg dose had greater treatment effect than 150 mg for all endpoints in overall population and most subgroups. Conclusions Machine learning identified predictors for additional benefit of secukinumab 300 mg compared with 150 mg dose. Individual patient efficacy meta-analysis showed that secukinumab 300 mg provided greater improvements compared with 150 mg in higher hurdle efficacy endpoints in patients with active PsA in the overall population and most subgroups with various levels of baseline disease activity and psoriasis.

Background C-reactive protein (CRP) is often normal in patients with psoriatic disease. Herein, we aimed to define markers of systemic inflammation in patients with monomorphic and polymorphic psoriatic skin, entheseal, and joint disease. Methods Three-step approach: (i) selection of serum markers elevated in psoriatic arthritis compared healthy controls from a panel of 10 different markers reflecting the pathophysiology of psoriatic disease; (ii) testing of these selected markers as well as C-reactive protein (CRP) in a larger cohort of 210 individuals- 105 healthy controls and 105 patients with psoriatic disease with either monomorphic skin (S), entheseal (E) or joint (A) involvement or polymorphic disease with various combinations of skin, entheseal and joint disease (SE, SA, EA, SEA); (iii) testing whether tumor necrosis factor (TNF) and interleukin (IL)-17 inhibitor therapy normalizes these markers. Results CRP was not elevated or was rarely elevated in the subgroups (S 0%, E 0%, A 20%, SE 7%, SA 33%, EA 27%, SEA 33%) despite active psoriatic disease. In sharp contrast, beta-defensin 2 and lipocalin-2 levels were elevated in the majority of patients with monomorphic skin (93% and 73%) and entheseal (both 53%), but not joint disease (27% and 20%). Conversely, elevations of calprotectin and IL-8 were found in the majority of patients with monomorphic joint disease (both 73%). IL-22 was elevated in all three monomorphic disease manifestations (S 60%, E 46%; A 60%). Furthermore, the vast majority of patients with polymorphic psoriatic disease (SE, SA, EA, SEA) showed widespread marker elevation. IL-17- and TNF inhibitor treatment significantly lowered all 5 markers of inflammation in PsA patients. Conclusions Systemic inflammation is detectable in the majority of patients with psoriatic disease, even if CRP is normal. The respective marker pattern depends on the manifestation of psoriatic disease with respect to skin, entheseal, and joint involvement.

Monomeric serum immunoglobulin A (IgA) can contribute to the development of various autoimmune diseases, but the regulation of serum IgA effector functions is not well defined. Here, we show that the two IgA subclasses (IgA1 and IgA2) differ in their effect on immune cells due to distinct binding and signaling properties. Whereas IgA2 acts pro-inflammatory on neutrophils and macrophages, IgA1 does not have pronounced effects. Moreover, IgA1 and IgA2 have different glycosylation profiles, with IgA1 possessing more sialic acid than IgA2. Removal of sialic acid increases the pro-inflammatory capacity of IgA1, making it comparable to IgA2. Of note, disease-specific autoantibodies in patients with rheumatoid arthritis display a shift toward the pro-inflammatory IgA2 subclass, which is associated with higher disease activity. Taken together, these data demonstrate that IgA effector functions depend on subclass and glycosylation, and that disturbances in subclass balance are associated with autoimmune disease., Immunoglobulin A (IgA) has two subclasses, IgA1 and IgA2, but differential effects on inflammation are unclear. Here the authors show that IgA2, when compared with IgA1, has stronger pro-inflammatory functions associated with changed glycosylation and higher disease scores in patients with rheumatoid arthritis.

Objective Recent guideline updates have suggested de-escalating DMARDs when patients with rheumatoid arthritis achieve remission or low disease activity. We aim to evaluate whether it is cost-effective to de-escalate the biological form of DMARDs (bDMARDs). Methods Using a Markov model, we performed a cost-utility analysis for RA patients on bDMARD treatment. We compared continuing treatment (standard care) to a tapering approach (i.e., an immediate 50% dose reduction), withdrawal (i.e., an immediate 100% dose reduction) and tapering followed by withdrawal of bDMARDs. The parametrization is based on a comprehensive literature review. Results were computed for 30 years with a cycle length of three months. We applied the payer’s perspective for Germany and conducted deterministic and probabilistic sensitivity analyses. Results Tapering or withdrawing bDMARD treatment resulted in ICERs of €526,254 (incr. costs -78,845, incr. QALYs -0.1498) or €216,879 (incr. costs -€121,691, incr. QALYs -0.5611) compared to standard care. Tapering followed by withdrawal resulted in a loss of 0.4354 QALYs and savings of €107,969 per patient, with an ICER of €247,987. Deterministic sensitivity analysis revealed that our results remained largely unaffected by parameter changes. Probabilistic sensitivity analysis suggests that tapering, withdrawal and tapering followed by withdrawal were dominant in 39.8%, 28.2% and 29.0% of 10,000 iterations. Conclusion Our findings suggest that de-escalating bDMARDs in patients with RA may result in high cost savings but also a decrease in quality of life compared to standard care. If decision makers choose to implement de-escalation in daily practice, our results suggest the tapering approach.

Objective Psoriasis is a systemic inflammatory disease often accompanied by comorbidities, including metabolic syndrome, cardiovascular diseases and depression. Up to 41% of psoriasis patients develop psoriatic arthritis (PsA), making it one of the most relevant manifestations. A large health claims data set was analysed to determine the rate of PsA development in psoriasis patients. Furthermore, comorbid disease profiles of psoriasis patients with or without PsA were compared, and potential risk factors for the development of PsA were identified. Methods This was a non-interventional, retrospective analysis of anonymized insurance health claims data using a subset of the Institute of Applied Health Research Berlin (InGef) database. The primary outcome was the prevalence and incidence of diagnosed PsA among psoriasis patients in Germany. Risk factors for the development of PsA in psoriasis patients were determined by conditional logistic regression analysis. Results The cumulative percentage of patients with existing psoriasis developing concomitant PsA over 4 years was 3.44%, with a mean time to diagnosis of PsA of 1.5 years. Psoriasis patients diagnosed with acute rheumatism (odds ratio: 2.93, 95% CI = 1.76, 4.86; P Conclusions Unspecific arthritic symptoms are likely to precede PsA diagnoses and can develop soon after onset of psoriasis, with accumulating risk over time. There is a high unmet need for early rheumatological assessment of psoriasis patients.

Objective Few studies have systematically and quantitatively addressed the impact of urate-lowering therapy on monosodium urate (MSU) deposits. This study was undertaken to analyze the effect of lifestyle measures and conventional urate-lowering therapy on MSU deposits in patients with gout. Methods In this prospective study, subjects with gout according to the American College of Rheumatology/European League Against Rheumatism classification criteria and presence of MSU deposits seen on dual-energy computed tomography (DECT) scans received either lifestyle intervention or conventional urate-lowering therapy for a mean period of 18 months before a follow-up DECT scan. Detected MSU deposits were quantified by volumetric measurement and validated by semiquantitative scoring, and baseline and follow-up measurements were compared. Results Baseline and follow-up DECT scans were available for all 83 subjects. Six subjects discontinued treatment, and 77 subjects underwent a lifestyle intervention (n = 24) or were treated with allopurinol (n = 29), febuxostat (n = 22), or benzbromarone (n = 2) over the entire observation period. The mean serum uric acid (UA) level decreased from 7.2 to 5.8 mg/dl in the overall population. In patients who discontinued treatment, no change in MSU deposits or serum UA levels was observed. The burden of MSU deposits significantly decreased in patients undergoing lifestyle intervention (MSU volume P = 0.007; MSU score P = 0.001), and in patients treated with allopurinol (MSU volume and score P < 0.001) or febuxostat (MSU volume P < 0.001; MSU score P = 0.001). No significant decline in MSU deposits was noted in patients who discontinued treatment. Conclusion These data show that lifestyle intervention and xanthine oxidase inhibitors significantly decrease the MSU deposit burden. Hence, conventional gout therapy not only lowers serum UA levels, but also reduces pathologic MSU deposits.

Background: Inflammatory-rheumatic diseases affect hand joints with swelling and pain, leading to joint destruction. Even patients with psoriasis only may suffer subclinical inflammation in the hand joints, leading to changes of bone [1]. Finger joint involvement is different for rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Pso) but hand function in these patients is not well characterized. Objectives: To quantify and compare grip strength and hand function in patients with RA, PsA and Pso and to relate these outcomes to disease activity. Methods: Patient diagnosed with RA (ACR/EULAR 2010), PsA (Caspar) and Pso and 54 healthy individuals were included in the study after written informed consent. Maximal isometric grip strength (kPA) was measured with a hand dynamometer (Lafayette Instrument, Lafayette, IN, USA) as the highest value out of three measurements. Hand function was determined by way of the Moberg Picking-Up Test (MPUT) and the fastest (s) of two measurements was used. Disease activity was calculated as DAS28_ESR and TJC/SJC 78/76 was recorded. One-way Analysis of Variance (ANOVA), factorial ANOVA and Games-Howell post-hoc testing was performed (p Results: 101 RA (63 f; 38 m; age: 59.1±13.2 yrs), 92 PsA (48 f, 44 m; age 54.8±11.6 yrs) and 51 Pso patients (19 f, 32 m; age 47.3±14.1 yrs), as well as 54 healthy control subjects (30 f, 24 m; age 54.6± 16.5 yrs) participated in the study. Disease duration (yrs) was not different between groups (RA: 11.03±10.1, PsA: 9.1±9.75, Pso: 12.5±11.7; p=0.156) but Pso patients in our cohort were younger compared to RA and PsA patients. Mean DAS28_ESR was Conclusion: Overall, RA patients showed significantly lower grip strength compared to PsA and Pso patients as well as to the control group, whereas all three patient groups performed worse in the MPUT compared to the control cohort. This suggests that grip strength may be preserved longer than hand function in patients with inflammatory rheumatic disease. Further, it was surprizing that hand function was reduced in Pso patients without arthritic correlate compared to healthy subjects. This suggests that hand function may provide a potential parameter for discriminating Pso patients at risk for subclinical joint involvement. This study was funded by research support from Novartis Pharma, GmbH. References [1] Faustini F, Simon D, et al. 2016, Ann Rheum Dis 75: 2068-2074. Disclosure of Interests: Anna-Maria Liphardt Grant/research support from: Novartis Pharma GmbH, Sonja Liehr: None declared, Eva Manger: None declared, Lisa Bieniek: None declared, Arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: Abbvie, David Simon Grant/research support from: Novartis, Consultant for: Lilly, Speakers bureau: Janssen, Koray Tascilar: None declared, Michael Sticherling: None declared, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Georg Schett: None declared, Axel Hueber Grant/research support from: Novartis, Pfizer, Consultant for: Lilly, Speakers bureau: Lilly, Novartis, Janssen, Abbvie

Background: Persistent drug-free remission of RA is a condition that is close to “cure” of the disease. However, long-term drug-free remission is considered to be rare and very challenging to reach. Also, little data are available that report how often persistent drug-free remission can be achieved and what kind of clinical characteristics are associated with such state. Objectives: To evaluate factors associated with persistent drug-free remission in patients with rheumatoid arthritis Methods: We analyzed the long-term observational follow-up phase of the randomized controlled RETRO (REduction of Therapy in RA Patients in Ongoing Remission) study on tapering and stopping of DMARDS in RA patients in stable remission (DAS28-ESR Results: All 141 patients being in the long-term observational follow-up phase of the RETRO study for at least 1 year were analyzed. Among them DMARDs were initially continued (Control, n=38), tapered (Taper, n=50) or stopped (Taper/Stop n=53). 19/141 patients were lost to follow-up and the worst case scenario was assumed that all of them did not reach persistent drug-free remission. Median time after study entry (Q1-Q3) was 69 (37-96) months as by December 2018. Overall number of patients in drug-free remission was 34/141 (24.1%), 10/38 (26%) in the control group, 6/50 (12%) in the taper group and 18/53 (34%) in the taper/stop group. After adjustment for baseline risk factors in the likelihood to reach persistent drug-free remission between the groups (OR:0.76, 95%CI: 0.29-1.99) was highly uncertain. Positive ACPA (OR: 3.38, 1.01 – 11.31) and erosive-state (3.05, 1.32 – 7.06) at baseline were associated with a lower likelihood to reach persistent drug-free remission. Conclusion: These data show that persistent drug-free remission can be reached in a subset of RA patients following a structured DMARD tapering approach after being in stable long-term DMARD control. References: [1] Haschka J, et al. Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis. 2016 Jan;75(1):45-51. [2] Rech J, et al. Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment. Ann Rheum Dis 2016;75:1637-44. Disclosure of Interests: Larissa Valor: None declared, Melanie Hagen: None declared, Michaela Reiser: None declared, Arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: Abbvie, Fabian Hartmann: None declared, Bernhard Manger: None declared, Georg Schett: None declared, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Koray Tascilar: None declared

Background: In contrast to rheumatoid arthritis, little is known about the effect of disease modifying anti-rheumatic drugs (DMARDs) on bone structure and bone biomechanics in psoriatic arthritis (PsA). Objectives: To address whether the use of methotrexate (MTX) and biological DMARDs (bDMARDs) impacts bone structure and biomechanical properties in PsA patients. Methods: Cross-sectional study in PsA patients receiving no DMARDs, MTX or bDMARDs. Volumetric bone densities (vBMD), microstructural parameters and biomechanical properties (stiffness/failure load) were determined by high-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis. Bone parameters were compared between PsA patients with no DMARDs and those receiving any DMARDs, MTX or bDMARDs, respectively. Results: 165 PsA patients were analyzed, 79 received no DMARDs, 86 received DMARDs, of them 52 bDMARDs (TNF, IL-17- or IL-12/23 inhibitors) and 34 MTX. Groups were balanced for age, sex, comorbidities, functional index and bone-active therapy, while disease duration was longest in the bDMARDs group (7.8±7.4 years), followed by the MTX group (4.6±7.4) and the no-DMARD group (2.9±5.2). No difference in bone parameters was found between the no-DMARD group and the MTX group. In contrast, the bDMARDs group revealed significantly higher total (p=0.001) and trabecular vBMD (p=0.005) as well as failure load (p=0.012) and stiffness (p=0.012). In regression models age and bDMARDs influenced total vBMD, while age, sex and bDMARDs influenced failure load and stiffness. Conclusion: Despite longer disease duration bDMARDs treated PsA patients benefit from higher bone mass and better bone strength than PsA patients receiving MTX or no DMARDs. These data support the concept of better control of PsA-related bone disease by bDMARDs. Disclosure of Interests: David Simon Grant/research support from: Novartis, Consultant for: Lilly, Speakers bureau: Janssen, Sara Bayat: None declared, Koray Tascilar: None declared, Eleni Kampylafka: None declared, Timo Meinderink: None declared, Louis Schuster: None declared, Anna-Maria Liphardt Grant/research support from: Novartis Pharma GmbH, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Axel Hueber Grant/research support from: Novartis, Pfizer, Lilly, Consultant for: Lilly, GSK, Novartis, Janssen, Celgene, Abbvie, Roche, Speakers bureau: Lilly, Janssen, Novartis, Celgene, Biogen, Abbvie, BMS, Georg Schett: None declared, Arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: Abbvie

Background: 18F-FDG-PET/CT is a sensitive and comprehensive technique to diagnose giant cell arteritis (GCA) (1). This technique may be also very useful to test whether vascular inflammation in GCA has disappeared or not, judging effectiveness of anti-inflammatory treatment. However, the role of 18F-FDG-PET/CT in monitoring disease activity and judging disease remission is less well-established to date Objectives: RIGA is an observational 2-center study that addresses the resolution of vascular inflammation in patients with new-onset GCA that are treated with either glucocorticoid monotherapy (GLC), GLC/methotrexate (MTX) or GLC/tocilizumab (TOC). Methods: Patients with newly diagnosed GCA with large vessel involvement were clinically documented, subjected to sequential 18F-FDG-PET/CT scanning and received treatment with GLC, MTX or TOC upon physicians’ decision. Images were graded as active, questionable active and inactive according to nuclear medicine physician opinion and additionally graded by PETVAS score proposed by Grayson et al. (0-27) (2). We performed a mixed effects linear regression analysis to estimate the change in the PETVAS score adjusted by baseline CRP level and tested for treatment group interactions. We compared the proportion of radiologic activity states according to the activity tracer uptake in the follow up 18F-FDG-PET/CT scan in three treatment groups with a chi-squared test. Results: We included 48 patients (n=20 from Germany, n=28 from Italy) with a mean age of 66 years. At baseline 18F-FDG-PET/CT scan was graded active in 46 patients while it was graded as questionable active in the remaining 2 patients. The mean CRP level was 66,8 mg/L (min 1,2; max 233,2 mg/l) and the mean PETVAS score was 21,1 (min=10 max=27). 12 patients received GLC, 27 MTX and 9 TOC as primary treatment. Follow-up PET/CT scans were graded as active in 11, questionable in 16 and inactive in 21 patients. The mean CRP level at follow up was 12,4 mg/l (min 0,2; max 76,0) and the mean PETVAS score was 9,1 (min 0, max 27) with significant decreases in all 3 groups. The mean adjusted improvement in the PETVAS score (95%CI) was 13.0 (8.7 – 17.3) in GLC, 11.7 (8.9 – 14.6) in MTX and 11.8 (6.8 – 16.7) in TOC groups and interaction terms for treatment effect were not significant. However, only 17% of patients who received GLC showed no vasculitis activity in their follow up PET-CT compared to 53% of patients who received MTX or TOC (figure 1). Conclusion: GLC, MTX and TOC significantly reduced vascular inflammation in GCA, but no significant differences between the three treatment strategies was found in this yet small population. However, when looking at complete resolution of vascular inflammation, MTX and TOC appear as being superior to GLC monotherapy, suggesting that addition of these agents right from the beginning of treatment of GCA may be beneficial to achieve complete control of vascular inflammation References: [1] Schonau V, et al. The value of 18F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study. Ann Rheum Dis. 2018Jan;77(1):70-77doi: 10.1136/annrheumdis-2017-211687 [2] Grayson, P. C. et al, 18F‐Fluorodeoxyglucose–Positron Emission Tomography As an Imaging Biomarker in a Prospective, Longitudinal Cohort of Patients With Large Vessel Vasculitis. Arthritis Rheumatol, 70: 439-449 doi:10.1002/art.40379 Disclosure of Interests: Verena Schonau Speakers bureau: Novartis (less than 2000 Euros), Jessica Roth: None declared, Koray Tascilar: None declared, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Daniela Schmidt: None declared, Torsten Kuwert: None declared, Filippo Crescentini: None declared, Luigi Boiardi: None declared, Massim iliano Casali: None declared, Annibale Versari: None declared, Georg Schett: None declared, Carlo Salvarani Grant/research support from: Roche, Consultant for: Eli Lilly and Company, Roche, Abbvie, Francesco Muratore: None declared

Background Psoriasis (PsO) and psoriatic arthritis (PsA) differentially impact patients’ quality of life (QoL) due to pain, mental changes in the context of chronic inflammation and impaired physical function. Effective anti-inflammatory therapy has shown to be effective to improve QoL in PsO and PsA patients. However, the impact of ant-inflammatory therapy on QoL may be different in the earliest stages of PsA as compared to established disease. Objectives To perform a detailed comparative investigation of the effect of interleukin (IL)-17 inhibition with 300 mg secukinumab (SEC) on QoL in patients with very early PsA/pre-PsA and established PsA. Methods Patients from the IVEPsA study (1) on very early PsA/pre-PsA (N=20) and the PSARTROS (2) study on established PsA (N=20) were longitudinally assessed for SF-36, DLQI, PsAID and HAQ-DI at baseline and after 4, 12 and 24 weeks. All patients received SEC treatment; 19/20 pre-PsA patients and 17/20 established PsA patients completed the study. Changes from baseline values were evaluated using linear mixed effects models adjusted for baseline values of each scale, gender, age and disease duration, and plotted as model coefficients and respective 95% confidence intervals that represent adjusted mean absolute improvement from baseline. Scale signs were inverted as necessary to ease interpretability. Further subgroup analysis was conducted using Mann-Whitney. Results Significant and rapid improvements were observed in both pre-PsA and established PsA treated with SEC with regard to pain (SF-36 bodily pain, BP), general health perception (GH), dermatology quality of life index (DLQI) and PsA impact of disease (PsAID), as well as in the SF-36 component scores (mental component score of SF-36, MCS and physical component score of SF-36, PCS). Physical function- oriented instruments like SF-36 physical functioning (PF), role limitation due to physical problem (RP) and HAQ-DI were preferentially affected in established PsA group due to the higher functional burden of disease (Figure). There were more differences with respect to the course of QoL improvements through week 12 and 24, as established PsA patients showed an incremental improvement in SF-36 BP, PF and GH from week 12 to 24 while most of the responses plateaued in the pre-PsA group. Furthermore, established PsA patients who achieved minimal disease activity showed a significantly higher improvement in PsAID, HAQ-DI, SF-36 PF, RP and BP (all p Conclusion Pain, mental health, general health perception and impact of disease rapidly improve in both very early PsA/pre-PsA and established PsA patients treated with SEC. These data support the concept that very early treatment of PsA leads to significant improvement in QoL with the additional benefit of prevention of bone damage as previously shown (1, 2). References [1] OP0305 Disease interception in psoriasis patients with subclinical joint inflammation by interleukin 17 inhibition with secukinumab – data from a prospective open label study. Kampylafka et al, aRD June 2018, Volume 77, Suppl. 2 [2] Resolution of synovitis and arrest of catabolic and anabolic bone changes in patients with psoriatic arthritis by IL-17A blockade with secukinumab: results from the prospective PSARTROS study. Kampylafka et al, arthritis Res ther. 2018Jul27;20(1):153 Acknowledgement This study was supported by an unrestricted grant from Novartis. Disclosure of interests Eleni Kampylafka: None declared, Matthias Englbrecht Grant/research support from: Roche Pharma aG, Chugai Pharma Europe Ltd., Consultant for: Roche Pharma aG, Chugai Pharma Europe Ltd., abbVie Deutschland GmbH & Co. KG, Celgene GmbH, Lilly Deutschland GmbH, Speakers bureau: Roche Pharma aG, Chugai Pharma Europe Ltd., abbVie Deutschland GmbH & Co. KG, Celgene GmbH, Lilly Deutschland GmbH, Koray Tascilar: None declared, Veronika Lerchen: None declared, Christina Linz: None declared, arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: abbvie, David Simon Grant/research support from: Novartis, Consultant for: Lilly, Speakers bureau: Janssen, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi aventis, and UCB (in total more than $10,000), Georg Schett: None declared, axel Hueber Grant/research support from: Novartis, Pfizer, Consultant for: Lilly, Speakers bureau: Lilly, Novartis, Janssen, abbvie

Background: Gout is based on the deposition of monosodium urate (MSU) crystals. While it is well established that life-style intervention and/or conventional urate lowering therapy can lead to a decrease in serum urate levels, the impact of such interventions to resolve already existing MSU deposits is very limited. Objectives: In this study we wanted to determine if and to what extent MSU deposits resolve if patients follow structured life-style intervention or continuously conventional urate lowering therapy. Methods: Subjects with diagnosis of gout and the presence of MSU deposits in the feet in baseline dual energy CT (DECT) scan, received either life-style intervention only (N=24) or additional conventional urate lowering therapy (allopurinol: N=29, febuxostat: N=22, benzbromarone N=2) for a mean period of 18 months before receiving a follow-up DECT examination. MSU deposits were quantified by volumetric measurement and semi quantitative scoring at baseline and follow up. Results: Serum uric acid (SUA) level decreased from 7.2±1.7 to 6.7±1.7mg/dl with life-style intervention; from 7.0±1.5 to 5.5±1.8mg/dl with allopurinol and from7.8±3.0 to 5.1 ± 2.5mg/dl with febuxostat. MSU volume significantly decreased in patients undergoing life-style intervention (baseline: 0,07cm3 ± 0,09; follow up: 0,05 ± 0,15cm3; p=0.007), treatment with allopurinol (0,11 ± 0.15 cm3 to follow up: 0.02 ± 0,04 cm3, p Conclusion: We show that both life-style intervention and conventional urate lowering drug therapy reduce the volume of monosodium urate deposits. The size of MSU deposits, but not serum urate level, was the main factor that influenced complete resolution of deposits. This finding reemphasizes that the burden of deposits essentially defines the likelihood and time for complete resolution of gout. References [1] Manger B, Lell M, Wacker J, Schett G, Rech J. Detection of periarticular urate deposits with dual energy CT in patients with acute gouty arthritis. Ann Rheum Dis. 2012;71(3):470-2. [2] Bongartz T, Glazebrook KN, Kavros SJ, Murthy NS, Merry SP, Franz WB, 3rd, et al. Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study. Ann Rheum Dis. 2015;74(6):1072-7. [3] Bayat S, Aati O, Rech J, Sapsford M, Cavallaro A, Lell M, et al. Development of a Dual-Energy Computed Tomography Scoring System for Measurement of Urate Deposition in Gout. Arthritis Care Res (Hoboken). 2016;68(6):769-75. Disclosure of Interests: Sara Bayat: None declared, Hanna Ellmann: None declared, Elizabeth Araujo: None declared, Bernhard Manger: None declared, Melanie Hagen: None declared, Arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: Abbvie, Alexandeer Cavallaro: None declared, Michael Lell: None declared, Hannah Schenker : None declared, David Simon Grant/research support from: Novartis, Consultant for: Lilly, Speakers bureau: Janssen, Koray Tascilar: None declared, Herbert S.B. Baraf: None declared, Georg Schett: None declared, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000)

Background Primary hand osteoarthritis (HOA) is a heterogeneous disease that is associated with erosive and osteoproliferative changes of the finger joints and progressive functional impairment. Despite these severe changes the effect of HOA on bone mass, microstructure and biomechanics in the affected skeletal regions is largely unknown. Objectives To study the effect of HOA on bone microstructure, density and biomechanical properties using high-resolution peripheral quantitative computed tomography (HR-pQCT) of the finger joints and radius. Methods HOA patients and healthy controls (HC) underwent HR-pQCT scans of the distal radius and 2nd metacarpal (MCP 2) head. Total, trabecular and cortical volumetric bone mineral densities (vBMD) as well as microstructural and biomechanical properties (failure load) were determined. Failure load and scaled multivariate outcome matrices from distal radius and 2nd metacarpal (MCP 2) head measurements were analyzed using multiple linear regression adjusting for age, sex and functional status and reported as adjusted z score differences for total and direct effects. Results 105 subjects were included (76 HC/29 HOA). After adjustment, HOA was associated with significant changes in the multivariate outcome matrix of the MCP 2 head (p Conclusion HOA is associated with reduced trabecular and increased cortical bone mineral density and a reduction in radial bone strength. Impaired mobility might be an explanation for this reduction. These results underline the clinical importance of HOA-related functional impairment and indicate that HOA patients should be treated with awareness of increased fracture risk and antiosteoporotic treatment. Disclosure of interests David Simon Grant/research support from: Novartis, Consultant for: Lilly, Speakers bureau: Janssen, Koray Tascilar: None declared, Sarah Unbehend: None declared, Sara Bayat: None declared, Timo Meinderink: None declared, andreas Berlin: None declared, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi aventis, and UCB (in total more than $10,000), axel Hueber Grant/research support from: Novartis, Pfizer, Lilly, Consultant for: Lilly, GSK, Novartis, Janssen, Celgene, abbvie, Roche, Speakers bureau: Lilly, Janssen, Novartis, Celgene, Biogen, abbvie, BMS, Georg Schett: None declared, arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: abbvie

Background Polyautoimmunity has been described to be associated with primary Sjogren’s syndrome (SjS) and the most frequent observed associated autoimmune diseases (AID) are autoimmune thyroid disease, autoimmune hepatitis and primary biliary cirrhosis, which are common organ-specific AID. In the same track, renal and lung involvement has increasingly been documented in SjS further highlighting its systemic nature. Objectives To describe and classify prevalence of polyautoimmunity and major organ involvement in a primary SjS-cohort. Methods This cross-sectional study included 179 patients [160 (89%) females and 19 (11%) males] diagnosed with primary SjS and fulfilling the ACR classification criteria (1) that had been admitted to our outpatient clinic between December 2008 and December 2018. Demographic and disease-specific characteristics were recorded in all patients. Results In our cohort the median age at diagnosis was 57 years (range: 20-85). Thyroid AID was found in 55/179 (30%) patients, with the following distribution: Hashimoto thyroiditis without (n=21) and with hypothyroidism (n=22), Graves’s disease without (n=4) and with thyroidectomy (n=8). Liver AID was detected in 8/179 patients (4%), 3 patients with autoimmune hepatitis and 5 patients with primary biliary cirrhosis. Regarding major organ involvement, 20/179 (11%) patients had renal manifestations: renal insufficiency (n=12), glomerulonephritis (n= 3), interstitial nephritis (n=2) and IgA nephritis (n=3). Eight/179 (4%) patients had lung manifestations: interstitial fibrosis (n=6), emphysema (n=1) and chronic obstructive pulmonary disease (n=1). Conclusion Our results add evidence for the presence of polyautoimmnunity and major organ involvement in SjS. We found a slightly lower prevalence of polyautoimmunity and major organ involvement compared to recently reported data (2). Nonetheless, extra-glandular organ involvement should be assessed in order to elucidate cumulative damage and how it might impact outcome, prognosis and therapeutic approaches in SjS. References [1] Shiboski SC, et al. American College of Rheumatology classification criteria for Sjogren’s syndrome: a data-driven, expert consensus approach in the Sjogren’s International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken) 2012;64(4):475-87. [2] Both T, et al. Reviewing primary Sjogren’s syndrome: beyond the dryness - From pathophysiology to diagnosis and treatment. Int J Med Sci. (2017) 23;14(3):191-200. Disclosure of Interests Larissa Valor: None declared, Hannah Schenker : None declared, Melanie Hagen: None declared, Johannes Knitza: None declared, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Georg Schett: None declared

Background Several studies including our own RETRO study have shown that tapering or stopping disease modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible (1-3). However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Objectives Here we analysed the impact of tapering or stopping DMARD treatment on the physical function of RA patients, who were randomized into continuation, tapering or stopping DMARD treatment in the RETRO study. Methods RETRO is a multicentre, parallel-group phase 3 trial in which RA patients in stable DAS-28-ESR remission were randomized to (i) DMARD tapering, (ii) stopping DMARDs after a 24-week-taper or (iii) control strategy that continued DMARDS.1,2,3 HAQ and DAS-28 scores were measured at 0, 3, 6, 9 and 12 months.1,2 Functional worsening was defined as a HAQ increase of≥0.25. We calculated incidences of functional worsening (per 100 person-months) in each treatment group with 95% Poisson confidence intervals and plotted event-free survival by treatment arm. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with control, taper or taper/stop group as the predictor. Results 201 patients were analysed. In 44 patients functional worsening was observed. Incidence (95%CI) of functional worsening was in the control 1.48 (0.77-2.59), taper 1.74 (0.95-2.92) and taper/stop arm 1.96 (1.16-3.10). The incidences suggest higher probability of functional worsening in tapering and/or stopping DMARDs, however at the end of study, functional worsening was similar among the groups (Figure). Thus, in comparison to the control group, hazard ratio (HR) (95%CI) for functional worsening was 1.21 (0.56 -2.62) in the taper arm and 1.32 (0.76-2.60) in the taper/stop arm. Conclusion Point estimates and survival curves show that functional decline after tapering or stopping DMARDs in RA patients with stable remission is small. Although the incidence figures suggest a trend these results do not reject with good certainty the null hypothesis of no worsening in functional status. Reference [1] Haschka, J. et al. 2016; 2 Rech, J. et al. 2016; 3 Hagen, M. et al. 2018 Disclosure of Interests Marlene Stephan: None declared, Koray Tascilar: None declared, Melanie Hagen: None declared, Judith Haschka: None declared, Michaela Reiser: None declared, Fabian Hartmann: None declared, Arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: Abbvie, Axel Hueber Grant/research support from: Novartis, Pfizer, Consultant for: Lilly, Speakers bureau: Lilly, Novartis, Janssen, Abbvie, Bernhard Manger: None declared, Camille Figuereido: None declared, Jayme Cobra: None declared, Hans-Peter Tony Consultant for: Eli Lilly and Company, Speakers bureau: Eli Lilly and Company, Stephanie Finzel: None declared, Stefan Kleinert Grant/research support from: Novartis, Consultant for: Novartis, UCB, Chugai, Celgene, Medac, Roche, Abbvie, Speakers bureau: Novartis, UCB, Chugai, Celgene, Medac, Roche, Abbvie, Joerg Wendler: None declared, Florian Schuch Consultant for: Celgene, Lilly, UCB, Roche, Sanofi-Aventis, Abbvie, Novartis, Speakers bureau: Celgene, Lilly, UCB, Roche, Sanofi-Aventis, Abbvie, Monika Ronneberger: None declared, Martin Feuchtenberger: None declared, Martin Fleck: None declared, Karin Manger: None declared, Wolfgang Ochs: None declared, Matthias Schmitt-Haendle: None declared, Hanns-Martin Lorenz: None declared, Hubert Nuesslein: None declared, Rieke Alten Grant/research support from: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, Jorg Henes: None declared, Klaus Krueger: None declared, Georg Schett: None declared, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000)

Background Development of rheumatoid arthritis (RA) is characterized by a several years lasting phase of autoimmunity, characterized by the presence of anti-modified protein antibodies (AMPA), recognizing citrullinated, carbamylated or acetylated proteins, as well as rheumatoid factor (RF) which precedes the onset of clinical disease (1,2).High resolution peripheral quantitative (HR-pQCT) technique enables the depiction of small cortical changes in peripheral joints (3). Objectives To describe microstructural bone lesions in rheumatoid arthritis (RA) at-risk individuals using HR-pQCT technique, their relation to rheumatoid arthritis specific autoimmunity, particularly osteoclast-inducing citrullinated vimentin (cVIM) antibodies and their impact on the later development of RA. Methods Cortical micro-channels (CoMiCs) as well as volumetric cortical and trabecular bone densities were analyzed by high-resolution computed tomography in the hand joints of RA at-risk individuals. Anti-modified protein antibody (AMPA) response was profiled including reactivities against citrullinated proteins (vimentin, enolase, fibrinogen) as well as carbamylated and acetylated vimentin. All subjects were followed for the development of RA. Results RA at-risk subjects (all N=75) with high-level (>1000U) cVIM antibodies showed a broader AMPA response and significantly more severe microstructural changes (higher CoMiCs, lower cortical and trabecular bone volume) compared to subjects with low/no cVIM reactivity. High cVIM antibodies and microstructural changes (>15 radial CoMiCs/joint) were associated with the presence of arthralgia. Furthermore, progression to RA was high in subjects with high cVIM (53%) vs. those with low (22%) or no (5%) antibodies and those with microstructural changes (46%) vs. those without such changes (16%). Conclusion: cVIM antibodies are associated to microstructural changes in RA at-risk individuals and predict the onset of RA. These data support the concept of structural priming of joints by autoimmunity before the onset of RA. References [1] McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365:2205-19. [2] Catrina AI, Svensson CI, Malmstrom V, Schett G, Klareskog L. Mechanisms leading from systemic autoimmunity to joint-specific disease in rheumatoid arthritis. Nat Rev Rheumatol. 2017;13:79-86. [3] Werner D, Simon D, Englbrecht M, et al. Early Changes of the Cortical Micro-Channel System in the Bare Area of the Joints of Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 2017;69:1580-7. Disclosure of Interests Arnd Kleyer Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: Abbvie, David Simon Grant/research support from: Novartis, Consultant for: Lilly, Speakers bureau: Janssen, Cong Duy Bui: None declared, Axel Hueber Grant/research support from: Novartis, Pfizer, Consultant for: Lilly, Speakers bureau: Lilly, Novartis, Janssen, Abbvie, Holger Bang Employee of: Dr. Bang is employee of the diagnostic company Orgentec Diagnostika., Andreas Ramming Grant/research support from: Novartis, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Gerhard Kronke Grant/research support from: Lilly, Pfizer, Speakers bureau: Novartis, Georg Schett: None declared

Background Psoriatic disease is composed of skin, entheseal and joint disease, which can manifest isolated or combined. Little is known about the systemic inflammation levels in psoriatic disease as a robust IL-6 signal is missing and therefore acute phase reactants such as C-reactive protein are often normal. Measuring systemic inflammation in the different manifestations of psoriatic disease is therefore a continuous unmet need. Objectives To better define systemic inflammation in patients with psoriatic disease limited to the skin (S), the entheses (E) or the joints (arthritis, A) or with a combination of these disease manifestations (SE, SA, EA, SEA). Methods Hypothesis-driven approach selecting markers that are (i) either targets of IL-23/IL-17 pathway activation (b-defensin 2, lipocalin 2, IL-22), (ii) associated with neutrophil/monocyte activation (calprotectin, IL-8) and (iii) achieve serum concentrations sufficient for reliable detection by standard ELISA. Parameters were assessed in 210 individuals comprising 105 healthy controls and 105 patients with psoriatic disease (each 15 for isolated (S, E, A) and composed disease manifestations SE, SA, EA, SEA). Results are expressed as percent positive patients with levels above three standard deviations over the mean level in healthy controls. In addition, 6-months sequential data on levels of these markers were collected in 20 patients treated with secukinumab or adalimumab to test treatment effects. Results CRP levels were normal in the majority of individuals. The respective percentages of patients with normal CRP ( 1.88 ng/mL) and lipocalin-2 (>24.7 ng/mL) were elevated in the majority of patients with isolated skin and entheseal, but not joint disease. Conversely, elevations of calprotectin (>3.58 mig/mL) and IL-8 (>10.3 pg/mL) were found in the majority of patients with isolated joint disease. IL-22 was elevated (>17.1 pg/mL) in all three manifestations of psoriatic disease. Reflecting a combination of the findings the vast majority of patients with composed disease manifestation (SE, SA, EA, SEA) showed widespread marker elevation. IL-17 and TNF inhibition differentially lowered and partially normalized elevated markers of inflammation. Conclusion Systemic inflammation is detectable in the majority of patients with psoriatic disease, even if CRP is normal. The respective marker pattern depends on the manifestation (skin, entheses, joints) of psoriatic disease, with beta-defensin 2 and lipocalin-2 reflecting skin and entheseal disease, calprotectin and IL-8 joint disease and IL-22 a combination of these disease manifestations. Disclosure of Interests Maria Sokolova Grant/research support from: M. Sokolova was a PARTNER Fellow, Celgene Sarl, Kemal Nas: None declared, Yubin Luo: None declared, David Simon Grant/research support from: Novartis, Consultant for: Lilly, Speakers bureau: Janssen, Yi Zhao: None declared, Jurgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Mario Zaiss: None declared, Georg Schett: None declared

To prevent serious complications such as permanent loss of vision and structural vascular damage, treatment must be initiated quickly in patients with giant-cell arteritis (GCA). So far, usually long-term corticosteroids in cumulative high dosages have been the standard therapy option. However, steroids are often insufficient to achieve adequate disease control and are associated with serious adverse events. Therefore, steroid-sparing therapy options are the focus of interest.

The polarization of macrophages is regulated by transcription factors such as nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1). In this manuscript, we delineated the role of the transcription factor Fos-related antigen 1 (Fra-1) during macrophage activation and development of arthritis. Network level interaction analysis of microarray data derived from Fra-1- or Fra-2-deficient macrophages revealed a central role of Fra-1, but not of Fra-2 in orchestrating the expression of genes related to wound response, toll-like receptor activation and interleukin signaling. Chromatin-immunoprecipitation (ChIP)-sequencing and standard ChIP analyses of macrophages identified arginase 1 (Arg1) as a target of Fra-1. Luciferase reporter assays revealed that Fra-1 down-regulated Arg1 expression by direct binding to the promoter region. Using macrophage-specific Fra-1- or Fra-2- deficient mice, we observed an enhanced expression and activity of Arg1 and a reduction of arthritis in the absence of Fra-1, but not of Fra-2. This phenotype was reversed by treatment with the arginase inhibitor Nω-hydroxy-nor-L-arginine, while ʟ-arginine supplementation increased arginase activity and alleviated arthritis, supporting the notion that reduced arthritis in macrophage-specific Fra-1-deficient mice resulted from enhanced Arg1 expression and activity. Moreover, patients with active RA showed increased Fra-1 expression in the peripheral blood and elevated Fra-1 protein in synovial macrophages compared to RA patients in remission. In addition, the Fra-1/ARG1 ratio in synovial macrophages was related to RA disease activity. In conclusion, these data suggest that Fra-1 orchestrates the inflammatory state of macrophages by inhibition of Arg1 expression and thereby impedes the resolution of inflammation.

Background:Serum concentration of cartilage oligomeric matrix protein (COMP) is related to the degree of cartilage destruction in patients with rheumatoid arthritis (RA) and shows a mechanosensitive response to ambulatory loads. We showed previously, that individuals with positive for anti-citrullinated protein antibody (ACPA+) status already show bone loss. It is unclear if these individuals experience cartilage deterioration and how this is related to physical activity.Objectives:To test whether soluble COMP levels in ACPA+ display the same response as RA patients after a walking exercise and explore the association between overall serum COMP levels and physical activity.Methods:RA patients and ACPA+ individuals (IRACE cohort: Individuals at Risk for Arthritis Cohort Erlangen; Ethics approval 334_16B) were enrolled in the study after written informed consent. Inclusion criteria were age between 18 and 69 years, RA (by 2010 ACR/EULAR criteria) or ACPA+ (without clinical manifestation of RA and prior treatment with glucocorticoids, DMARDs and biologics). The study comprised three visits (baseline (Visit 1), 6 (Visit 2), and 12 months (Visit 3). During each visit, serum samples were collected after 30 minutes rest (pre) and at 0, 30, 60, and 120 minutes after a 30-minute walking exercise. Serum COMP concentration was analyzed by commercial ELISA. Physical activity duration (hours) was measured using an activity monitor for 7 consecutive days, and physical activity level (metabolic equivalent of the task (MET)) was quantified using the International Physical Activity Questionnaire (IPAQ). The reponse of COMP levels to the walking exercise was modelled using linear mixed-effects regression models. The association between physical activity and overall serum COMP concentrations was analyzed using a mixed-effects regression model (Random effects: individuals, visits and COMP measurement time points).Results:28 RA and 22 ACPA+ patients participated in this prospective study. Table 1 summarizes patient demographics and outcome measures. Serum COMP levels increased in response to the walking exercise in both groups but the acute response was not different in RA patients compared to ACPA+ individuals. Higher physical activity level by IPAQ was associated with higher overall COMP concentration. Doubling of total physical activity is associated with an increase in serum concentration of 0.32 U/L (95%CI 0.09 to 0.54, p=0.006). ACPA+ individuals but not RA patients show an association between serum COMP concentration and physical activity duration (Figure 1).Table 1.Summary of subject characteristics and outcome measures.DescriptivesMeasureACPA+RAindividuals, number (%)22 (44.0)28 (56.0)Age, years (mean (SD))47.6 (12.8)57.0 (9.1)Female, number (%)14 (28.0)19 (38.0)BMI, kg/m2, mean (SD)25.1 (5.6)27.2 (5.8)Anti-CCP positive (N)1714DAS28-score, mean (SD)2.5 (1.2)2.7 (1.4)Cartilage Oligomeric Matrix Protein (U/l)Visit 1Visit 2Visit 3ACPA+RAACPA+RAACPA+RApre-walking exercise9.4 (2.8)9.7 (3.8)10.8 (2.2)11.3 (4.5)10.2 (2.5)10.5 (3.9)09.5 (2.6)10.4 (3.9)11.8 (1.8)12.2 (4.0)10.1 (2.0)11.1 (4.6)309.2 (2.2)9.9 (3.6)10.8 (1.9)11.4 (4.4)9.2 (2.2)10.6 (4.2)609.2 (2.0)9.4 (4.0)10.4 (2.1)10.9 (4.5)8.6 (2.9)10.0 (4.0)1209.2 (2.1)9.5 (4.0)9.6 (1.8)10.9 (4.4)8.0 (2.4)9.9 (3.9)Figure 1.Estimated marginal mean COMP by physical activity duration for RA and ACPA+.Conclusion:Pre-exercise serum COMP concentration is similar in ACPA+ and RA and shows a similar increase in response to walking in both groups. Physical activity duration appears to influence serum COMP concentration in ACPA+. Given that acute COMP release was not different between ACPA+ and RA while overall COMP values are associated with physical activity level, the discrepancy between ACPA+ and RA for this association can be explained by reduced vigor or qualitative differences in physical activity.Disclosure of Interests:Lisa Bleckwedel-Rolack: None declared, Koray Tascilar: None declared, Veronika Nees: None declared, Julia Hühne: None declared, Axel Hueber: None declared, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Georg Schett Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Arnd Kleyer Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Anna-Maria Liphardt Speakers bureau: Mylan, Paid instructor for: Abbvie, Consultant of: MEDA Pharma, Grant/research support from: Novartis

Background:Understanding key mechanisms of flare development and sustained remission is one of the acute goals in modern rheumatology. Anti-citrullinated protein antibodies (ACPA) are the most abundant and specific autoantibodies in rheumatoid arthritis (RA) patients. However, the impact of ACPA of IgA isotype is poorly defined. IgA ACPA were previously shown to have a higher percentage of IgA2 in comparison to total IgA; and a correlation between IgA2% ACPA with the DAS28 score was observed in a previous study [1]. Of note, IgA1 and IgA2 were shown to exhibit different effector functions, with IgA2 being pro-inflammatory, which might be the background for its role in RA [1].Objectives:We aimed to investigate, whether IgA ACPA could be used as a predictive factor for flare development in RA; and to look further into the changes in IgA ACPA levels in patients remaining in stable remission versus patients developing flare.Methods:We analysed serum of 111 patients from a multicentre randomized controlled trial ‘RETRO’. The study observational period was 12 months. Patients in the trial had to be in stable remission (DAS28-ESRResults:60% of patients had IgG-ACPA. IgA ACPA levels were higher among the IgG-ACPA-positive patients (median 4.7 versus 2.24 µg/ml, pConclusion:Neither IgA1 nor IgA2 ACPA levels were predictive of flare development or associated with treatment strategies (though rituximab, JAK-inhibitors and abatacept were not amongst treatment options). However, in patients remaining in sustained remission after 1 year a decrease in IgA2 and IgA2% ACPA was observed and IgA2% ACPA was associated with DAS28 score registered after flare. This could be an indication towards ACPA of IgA2 isotype contributing to the severity of flare, alongside other factors, and its reduction being associated with a prolonged state of remission.References:[1]Steffen U, Koeleman CA, Sokolova MV, et al. IgA subclasses have different effector functions associated with distinct glycosylation profiles. Nat Commun 11, 120 (2020).[2]Haschka J, Englbrecht M, Hueber AJ, et al. Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis. 75:45-51 (2016).Disclosure of Interests:None declared

Background:In clinical trials as well as in real-life, the IL-1ß inhibitor canakinumab leads to rapid remission of symptoms in the treatment of CAPS, a monogenic autoinflammatory disease with severe systemic and organ inflammation.Objectives:The RELIANCE registry is designed to explore long-term safety and effectiveness of canakinumab under routine clinical practice conditions in pediatric (≥2 years) and adult patients with CAPS, including Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal onset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome (CINCA).Methods:This prospective, non-interventional, observational study with a 3-year follow-up enrolls patients with clinically confirmed diagnoses of CAPS routinely receiving canakinumab. In 6-monthly visits, clinical data, physician assessments and patient-reported outcomes are evaluated starting at baseline with last update at 30 months of follow-up in the total cohort including the cohort with severe CAPS subtypes (NOMID/CINCA).Results:91 CAPS patients (50% female; 14 [15%] NOMID/CINCA subtypes) were enrolled by December 2020 (Table 1). At baseline, median age was 20.5 years and median duration of prior canakinumab treatment was 6 years. 11 drug related severe adverse events per 100 patient years were reported. 68% of patients reached disease remission by physicians´ assessment along with rates of 40-61% absent disease activity in PGA. Patients reported stable low level disease activity, fatigue and Auto-Inflammatory Diseases Activity Index scores (AIDAI, figure 1). CAPS was impairing social life in 50% of patients and another 50% reported days off from school/work. Lab parameters were within normal limits.Table 1.Patient and physician assessment of clinical CAPS disease activity and laboratory markers over time.Baseline12 months30 monthsTotal cohortNOMID/ CINCATotal cohortNOMID/ CINCATotal cohortNOMID/ CINCANumber of patients, N9114678284Number (%) of patients with days absent from work/school during last 6 months30 (34)4 (29)28 (42)2 (25)17 (61)4 (100)Number (%) of patients in disease remission (physician assessment)61 (68.5)11 (78.6)42 (66.7)4 (66.7)19 (67.9)4 (100.0)Physician Global Assessment, percentage of absent/mild-moderate/severe rating, %40 / 53 / 257 / 36 / 033 / 60 / 233 / 50 / 061 / 39 / 075 / 25 / 0Patient assessment of current disease activity; 0–10, median (min; max)2.0 (0; 7)1.0 (0; 6)1.0 (0; 7)1.0 (0; 5)0.0 (0; 7)0.0 (0; 4)Patient assessment of current fatigue; 0–10, median (min; max)3.0 (0; 9)2.0 (0; 6)3.0 (0; 8)2.0 (0; 8)1.0 (0; 8)4.0 (0; 5)Number (%) of patients without impairment of social life by the disease32 (52.5)4 (50.0)31 (62.0)3 (42.9)11 (47.8) 1 (33.3)CRP, median (mg/dl)0.10.20.10.50.00.2SAA, median (mg/dl)0.30.40.50.90.30.1ESR, median (mm/h)5.06.05.03.55.05.5SAENumber of eventsIncidence rate per 100 patient yearsTotal cohortNOMID/CINCATotal cohortNOMID/CINCAAll types of SAE39314.7211.72SADR20#010.690.00# Alport’s syndrome, appendicitis, blister, cardiovascular disorder, chest pain, circulatory collapse, erythema, febrile convulsion, glomerulonephritis, haemophilus test positive, pneumonia, premature delivery, skin discolouration, tonsillectomy, tonsillitis bacterial, tonsillitis streptococcal (all N=1 event), pyrexia (N=3 events), not yet coded (inpatient admission, N=1 event) CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reaction; SAE, serious adverse eventConclusion:The 30-month interim analysis of the RELIANCE study demonstrates that long-term canakinumab treatment is safe and effective in patients with any subtype of CAPS. However, impairment of social life and days off school/work still exists.Disclosure of Interests:J. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Birgit Kortus-Goetze Consultant of: Novartis, Prasad Oommen Grant/research support from: Novartis, Ales Janda: None declared, Jürgen Rech Speakers bureau: bbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Frank Weller-Heinemann: None declared, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ivan Foeldvari Consultant of: Novartis, Catharina Schuetz: None declared, Michael Borte Grant/research support from: Pfizer, Shire, Axel Braner Consultant of: Novartis and SOBI, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi

Objective To assess the 2-year efficacy and safety of the interleukin-17A inhibitor, secukinumab, in active psoriatic arthritis (PsA). Methods In the FUTURE-1 study, 606 patients with active PsA were randomized to secukinumab 10 mg/kg intravenously at baseline, and at weeks 2 and 4, followed by 150 mg or 75 mg subcutaneously (SC) every 4 weeks from week 8, or matching placebo. Patients receiving placebo were re-randomized to secukinumab 150 mg or 75 mg SC from week 16 or week 24, depending upon clinical response. Treatment continued to week 104. Exploratory analysis of all primary and secondary end points, on an intent-to-treat basis, continued to week 104. Results A total of 476 patients (78.5%) completed 104 weeks of treatment. Secukinumab showed sustained efficacy across multiple domains of PsA through week 104, including signs and symptoms, disease activity, quality of life, physical function, skin symptoms, dactylitis, and enthesitis. American College of Rheumatology criteria for 20% improvement response rates were 66.8% with secukinumab 150 mg and 58.6% with secukinumab 75 mg at week 104; Psoriasis Area and Severity Index criteria for 75% improvement response rates were 74.6% and 63.0%, respectively (multiple imputed data). At week 104, 84.3% of patients in the secukinumab 150 mg group and 83.8% in the secukinumab 75 mg group showed no radiographic disease progression (observed data). No new or unexpected safety signals were reported during 2 years of treatment. Immunogenicity to secukinumab was low. Conclusion Secukinumab provided sustained improvements in PsA at 2 years, with very little radiographic progression. Treatment was well tolerated over the long term.

Career situation of first and presenting author Student for a master or a PhD. Introduction The activator protein (AP)-1 transcription factor family, especially its subfamily of FOS proteins (cFos, FosB, Fra-1 and Fra-2) are associated to the regulatory network of macrophage responses. Moreover, it is well known that macrophages are central player during rheumatoid arthritis (RA). Objectives This study aims to delineate the role of Fra-1 in macrophages during the acute destructive inflammatory phase of RA. Methods Therefore, we applied the serum-induced arthritis (K/BxN) model to Fra-1 deficient mice controlled by the Mx1 promoter (Fra-1ΔMx) or the LysM promoter (Fra-1ΔLysM). Moreover, we performed in vitro analyses of macrophage polarization in wildtype and Fra-1 deficient macrophages, as well as micro-arrays and ChIP sequencing analyses to delineate Fra-1 targets in activated macrophages. We completed our analysis by studying Fra-1 expression in RA patients’ synovium. Results Fra-1 mutant mice had decreased arthritis severity compared to their littermate wildtype mice. The alleviated arthritis was accompanied to increased arginase-1 (Arg1) expression and activity in the joints, suggesting that its anti-inflammatory features milder RA inflammation. Sorting of immune cell populations revealed macrophages as the major source of Arg1, which was increased in Fra-1 mutant mice. Mechanistically, Fra-1 transcriptionally inhibited Arg1 expression in macrophages. Moreover, inhibition of Arginase in Fra-1 mutant mice restored a full blunt inflammatory RA response and the supplementation of mice with l-arginine, leading to increased arginase activity in the joint, is sufficient to milder arthritis. Synovium histological sections from RA patients showed a correlation between Arg1, Fra-1 and the DAS28 score, confirming that increased Arg1 activity is of benefit also for human inflammatory joint disease. Conclusions Our data show for the first time that Fra-1 is a pivot between pro- and anti-inflammatory macrophage. By inhibiting Arg1 activity, Fra-1 exacerbates RA inflammation and joint destruction. Disclosure of Interest None declared.

Background:We have previously reported that the presence of musculoskeletal pain in psoriasis patients is associated with a higher risk of developing psoriatic arthritis (PsA) (1). Furthermore, a subset of psoriasis patients shows evidence for structural entheseal lesions (SEL) in their hand joints (2), sometimes also referred as “Deep Koebner Phenomenon”, which are highly specific for psoriatic disease and virtually absent in healthy controls, rheumatoid arthritis and hand osteoarthritis patients (2-4). However, it remains unclear whether SEL alone or in combination with musculoskeletal pain are associated with the development of PsA.Objectives:To test whether the presence of SEL in psoriasis patients increases the risk for progression to PsA and how this is related to the presence of musculoskeletal pain.Methods:Psoriasis patients without evidence of PsA were enrolled in a prospective cohort study between 2011 and 2018. All patients underwent baseline assessment of SEL in their 2ndand 3rdMCP joints by high-resolution peripheral quantitative computed tomography (HR-pQCT). The risk of PsA development associated with SEL and arthralgia was explored using survival analyses and multivariable Cox regression models.Results:114 psoriasis patients (72 men/42 women) with a mean (SD) follow-up duration of 28.2 (17.7) months were included, 24 of whom developed PsA (9.7 /100 patient-years, 95%CI 6.2 to 14.5) during the observation period. Patients with SEL (N=41) were at higher risk of developing PsA compared to patients without such lesions (21.4/100 patient-years, 95%CI 12.5 to 34.3, HR 5.10, 95%CI 1.53 to 16.99, p=0.008) (Kaplan Meier plot A). Furthermore, while patients without arthralgia and without SEL had a very low progression rate to PsA (1/29; 3.4%), patients with arthralgia but no SEL showed higher progression (5/33; 15.2%), which was in line with previous observations (1) (Kaplan Meier plot B). Presence of SEL further enhanced the risk for progression to PsA both in the absence (6/16; 37.5%) and presence (6/14; 42.8%) of arthralgia with the highest progression rate in those subjects with both arthralgia and SEL (pConclusion:Presence of SEL is associated with an increased risk of developing PsA in patients with psoriasis. If used together with pain, SEL allow defining subsets of psoriasis patients with very low and very high risk to develop PsA.References:[1]Faustini F et al. Ann Rheum Dis. 2016;75:2068-2074[2]Simon D et al. Ann Rheum Dis. 2016;75:660-6[3]Finzel S et al. Ann Rheum Dis. 2011;70:122-7[4]Finzel S et al. Arthritis Rheum. 2011;63:1231-6Disclosure of Interests:David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Koray Tascilar: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Sara Bayat Speakers bureau: Novartis, Eleni Kampylafka Speakers bureau: Novartis, BMS, Janssen, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Louis Schuster: None declared, Klaus Engel: None declared, Michael Sticherling Grant/research support from: Novartis, Consultant of: Advisory boards Abbvie, Celgene, Janssen Cilag, Lilly, Pfizer, MSD, Novartis, Amgen, Leo, Sanofi, UCB, Speakers bureau: Abbvie, Celgene, Janssen Cilag, Leo, MSD, Novartis, Pfizer, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Background:Deposition of uric acid crystals cause an inflammatory reaction, which can lead to structural bone changes, if such deposits form adjacent to cortical bone [1, 2]. Both erosions and bony spurs can form in conjunction with tophus deposition. The exact spatial inter-relation between tophi and structural bone lesions in humans in vivo is not fully characterized.Objectives:To spatially relate structural bone changes (erosions, osteophytes) to the deposition of monosodium urate crystals in the first metatarsophalangeal (MTP1) joint in patients with tophaceous gout.Methods:Tophaceous gout patients with clinically detected tophi at the MTP1 joint underwent simultaneous dual energy computed tomography (DECT) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the feet. Tophi detected by DECT and erosions and osteophytes detected by HR-pQCT were overlayed to define their exact anatomical relation. Furthermore, feet of sex- and age-matched healthy controls (HC) were scanned to define the normal architecture of the MTP1 joint.Results:Gout patients (N=20) had significantly higher numbers (5 (0–17 vs. 1 (1– 2)) and volumes (45.32 mm3(7.26–550.32) vs. 0.82 mm3(0.15–21.8)) of bone erosions as well as significantly higher numbers (10.5 (0-26) vs. 1 (0-10)) and sizes of osteophytes (4.93 mm (0.77-7.19 mm vs. 0.93 mm (0.05-7.61 mm))than healthy controls (N=20). Erosions were in direct spatial relation to bone erosions, while osteophytic responses were more widespread and affected bone regions on the MTP1, which were not directly adjacent to tophi. Median tophus volume detected by DECT (0.12 mm3(0.01–2.53)) was associated with the total volume of erosions (r=0.597, p=0.005).Conclusion:This study demonstrates that bone changes in gout are substantial and not only include erosions but also widespread architectural bone remodeling associated osteophyte formation. While there is a direct spatial relation between tophi and bone erosions the anabolic bone responses in gout are more widespread.References:[1]Dalbeth, N. et al. Ann Rheum Dis. 2015 Jun;74(6):1030-6.[2]Dalbeth, N. et al. Arthritis Res Ther. 2012; 14(4): R165.Data are based on high-resolution peripheral quantitative computed tomography (HR-pQCT) of metatarsophalangeal joints I in gout patients (grey boxplots) and healthy controls (white boxplots). (A) number of bone erosions, (B) volume of bone erosions, (C) number of osteophytes and (D) size of osteophytes. Data are shown as medians and inter-quartile ranges (boxes).Distribution of (A) tophi based on dual-energy computed tomography (DECT) as well as (B) bone erosions and (C) osteophytes based on high-resolution peripheral quantitative computed tomography (HR-pQCT) of metatarsophalangeal (MTP) I head in gout patients. Data are shown for the different regions of the MTPI head including the plantar, medial, dorsal and lateral region of the metatarsal head, as well as the medial and lateral sesamoid bones. Data indicate percentage of patients with tophi, erosions and osteophytes in respective region.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Caroline Pecherstorfer: None declared, Hanna Ellmann: None declared, Camille Figueiredo: None declared, Matthias Englbrecht: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Background:In part 1 of the 52-week, double-blind GiACTA trial, patients with giant cell arteritis (GCA) who received weekly tocilizumab (TCZ) plus prednisone tapering reported improvement in the 36-item Short-Form Health Survey (SF-36) Mental Component Summary (MCS) and Physical Component Summary scores and FACIT-Fatigue scores that were statistically significant and clinically meaningful compared with patients who received prednisone alone.1Objectives:To analyze whether benefit in SF-36 MCS was maintained in patients originally assigned to TCZ compared with those originally assigned to placebo (PBO) plus a 26- or 52-week prednisone taper among patients who achieved clinical remission at week 52 and maintained treatment-free clinical remission in the 2-year, long-term extension of GiACTA.Methods:At the end of part 1, patients entered open-label part 2, in which GCA therapy (including initiation/termination of open-label TCZ and/or GCs) was given at the investigator’s discretion according to disease status. Change from baseline in SF-36 MCS score was compared for combined original TCZ (n = 33) and PBO (n = 17) patients who achieved clinical remission at week 52 and maintained treatment-free (no TCZ or GCs) clinical remission in part 2 using a repeated-measures model. The minimal clinically important difference (MCID) for SF-36 MCS is >2.5.2Results:During treatment, SF-36 MCS scores in all 50 patients who maintained treatment-free clinical remission in part 2 had diverged between the TCZ and PBO groups as early as 36 weeks after baseline, with greater improvements evident in the TCZ group (Figure). The difference in least square means (LSM) change between TCZ and PBO was statistically significant at week 52 (p= 0.016) and maintained at weeks 100 (p= 0.023) and 156 (p= 0.002). The LSM difference (95% CI) between TCZ and PBO at weeks 52, 100, and 156 was 5.6 (1.1-10.2), 6.5 (0.9-12.1), and 7.4 (2.9-11.9), respectively, exceeding the MCID.Conclusion:Among patients who maintained treatment-free clinical remission during part 2 of GiACTA, those originally assigned to receive TCZ plus a prednisone taper during part 1 maintained statistically significant and clinically meaningful improvements in SF-36 MCS up to week 156 compared with those originally assigned to receive PBO plus a prednisone taper in part 1. This was true even though neither of the patient groups received TCZ or GC treatment after they achieved clinical remission at week 52.References:[1]Strand V et al.Arthritis Res Ther2019;21:64.[2]Lubeck DP.Pharmacoeconomics2004;22:27-38.Disclosure of Interests:John H. Stone Grant/research support from: Roche, Consultant of: Roche, Jian Han Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Sebastian Unizony Grant/research support from: Genentech, Inc., Martin Aringer Consultant of: Boehringer Ingelheim, Roche, Speakers bureau: Boehringer Ingelheim, Roche, Daniel Blockmans Consultant of: yes, Speakers bureau: yes, Elisabeth Brouwer Consultant of: Roche (consultancy fee 2017 and 2018 paid to the UMCG), Speakers bureau: Roche (2017 and 2018 paid to the UMCG), Maria C. Cid Speakers bureau: Roche, Bhaskar Dasgupta Grant/research support from: Roche, Consultant of: Roche, Sanofi, GSK, BMS, AbbVie, Speakers bureau: Roche, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Carlo Salvarani: None declared, Robert Spiera Grant/research support from: Roche-Genetech, GSK, Boehringer Ingelheim, Chemocentryx, Corbus, Forbius, Sanofi, Inflarx, Consultant of: Roche-Genetech, GSK, CSL Behring, Sanofi, Janssen, Chemocentryx, Forbius, Mistubishi Tanabe, Min Bao Shareholder of: Roche, Employee of: Genentech

Background:Personalization of RA treatment is not optimal due to lack of predictors. We previously demonstrated in RA patients that central nervous system (CNS) pain response to tender joint compression, measured by using functional MRI (fMRI) of the brain rapidly wanes after 24 hours of anti-TNF administration and that a higher pre-treatment BOLD signal volume seems to predict clinical response to treatment with certolizumab-pegol (CZP)1,2. We therefore hypothesized that the CNS pain response upon compression of a painful joint could predict subsequent anti-TNF treatment response.Objectives:To compare disease activity after 12-weeks of CZP treatment to that of placebo in DMARD-refractory RA patients based on pre-treatment baseline CNS pain response measured using BOLD fMRI.Methods:Adult RA patients fulfilling the 2010 ACR/EULAR classification criteria with a DAS28>3.2 under stable DMARD treatment for at least 3 months were eligible. Patients underwent fMRI scanning of the brain at screening for stratification by CNS pain response. Whole brain BOLD-signal-voxel-count of 700 units classifying between low and high, and were randomized to CZP or placebo (2:1) The primary outcome was low disease activity (LDA, DAS28 ≤3.2) after 12 weeks of treatment.Results:156 RA patients, inadequate responders to csDMARD, signed the informed consent. 139 patients (46/47, 46/49 and 42/43) (99 females, 71%) with moderate-high disease activity (mean (SD) DAS-28: 4.83 (1.03)) could be included respectively and completed the 12-week study treatment. Geometric mean (SD) numbers of baseline BOLD signal positive voxels were 559 (10), 81 (12) and 2498 (3) in the 3 arms respectively. The mean DAS28 (SD) scores after 12 weeks of study treatment were Placebo: 3.89 (1.29), CZP-L: 3.42 (1.06) and CZP-H: 3.06 (1.04). LDA was achieved in 12/47 patients (25.5 %) in placebo, 22/49 (44.9%) in the CZP-L, and 25/43, (58.1%) in the CZP-H arm. The linear effect term for the ordinal study group variable supported a linear trend of increasing CZP treatment effect with increasing baseline CNS pain response. RR (95% CI) for achieving LDA with each unit increase in treatment category over placebo was 1.79 (1.24 to 2.74, p=0.003).Conclusion:A higher pre-treatment brain activity in response to pain measured with fMRI predicts the chance of achieving low disease activity with CZP treatment.References:[1] Hess, A.et al.PNAS (2011)[2] Rech, J.et al. Arthritis & Rheumatism(2013).Acknowledgments :The study was supported by an unrestricted grant from UCB Biopharma SPRL, Brussels, BelgiumDisclosure of Interests:Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Koray Tascilar: None declared, Hannah Schenker: None declared, Marina Sergeeva: None declared, Mageshwar Selvakumar: None declared, Laura Konerth: None declared, Jutta Prade: None declared, Sandra Strobelt: None declared, Melanie Hagen: None declared, Verena Schönau: None declared, Larissa Valor: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Frank Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Janssen, Consultant of: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Speakers bureau: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Christoph Baerwald Consultant of: CGB received speaker or consulting fees from AbbVie, Paid instructor for: CGB received speaker or consulting fees from AbbVie, Speakers bureau: CGB received speaker or consulting fees from AbbVie, Stephanie Finzel: None declared, Reinhard Voll: None declared, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Arnd Doerfler: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Andreas Hess: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Background:In part 1 of the 52-week, double-blind GiACTA trial, tocilizumab (TCZ) every week (QW) or every other week (Q2W) + prednisone tapering reduced the risk for flare versus placebo (PBO) + 26-week prednisone tapering among patients with new-onset giant cell arteritis (GCA) at baseline. Among patients with relapsing GCA, TCZ QW but not Q2W + prednisone reduced the risk for flare versus both PBO groups, and there was separation in the time to flare between the TCZ QW and Q2W groups.1Objectives:To report time to first flare and potential cumulative glucocorticoid (GC) sparing over 3 years of the GiACTA trial (part 1 + 2-year open-label part 2) among patients with new-onset or relapsing GCA.Methods:At the end of part 1, patients entered open-label part 2, in which GCA therapy (including initiation/termination of open-label TCZ and/or GCs) was given at the investigator’s discretion according to disease status. Time to first GCA flare during the 3-year study period was assessed using Kaplan-Meier analysis for patients in the intention-to-treat population according to disease onset status at baseline (new-onset/relapsing) based on their originally assigned treatment groups: TCZ QW, TCZ Q2W, or pooled PBO (PBO+26-week and PBO+52-week prednisone taper).Results:Among patients randomly assigned in part 1, 47 of 100 (47%) in the TCZ QW group, 26 of 49 (53%) in the TCZ Q2W group, and 46 of 101 (46%) in the pooled PBO group had new-onset GCA at baseline; the rest had relapsing GCA. Median time to first flare over 3 years was longer for patients assigned to TCZ treatment in part 1 than for patients assigned to PBO; Kaplan-Meier analysis showed a clear separation between the TCZ QW and the pooled PBO groups over 3 years for patients with new-onset and relapsing GCA (Figure 1A). Separation between the TCZ QW and TCZ Q2W groups was also observed over 3 years in patients with new-onset and relapsing GCA, although this was more evident in patients with relapsing GCA (Figure 1B). Higher proportions of patients in the TCZ QW group (new-onset, 49%; relapsing, 47%) than the pooled PBO group (new-onset, 28%; relapsing, 31%) and the TCZ Q2W group (new-onset, 27%; relapsing, 35%) remained flare-free during their entire treatment period. Cumulative prednisone dose over 3 years was lower for patients originally assigned to TCZ QW versus those originally assigned to PBO for patients with new-onset GCA and those with relapsing GCA at baseline (Figure 2).Conclusion:In this 3-year analysis of GiACTA parts 1 and 2, time to first flare favored TCZ QW over TCZ Q2W in patients with new-onset and relapsing GCA. TCZ QW delayed time to first flare and resulted in lower cumulative GC exposure compared with PBO in patients with new-onset and relapsing GCA, supporting TCZ QW dosing in patients with GCA regardless of disease onset.References:[1]Stone JH et al. N Engl J Med 2017;377:317-28.Disclosure of Interests:John H. Stone Grant/research support from: Roche, Consultant of: Roche, Helen Spotswood Shareholder of: Roche Products Ltd, Employee of: Roche Products Ltd, Sebastian Unizony Grant/research support from: Genentech, Inc., Martin Aringer Consultant of: Boehringer Ingelheim, Roche, Speakers bureau: Boehringer Ingelheim, Roche, Daniel Blockmans Consultant of: yes, Speakers bureau: yes, Elisabeth Brouwer Consultant of: Roche (consultancy fee 2017 and 2018 paid to the UMCG), Speakers bureau: Roche (2017 and 2018 paid to the UMCG), Maria C. Cid Speakers bureau: Roche, Bhaskar Dasgupta Grant/research support from: Roche, Consultant of: Roche, Sanofi, GSK, BMS, AbbVie, Speakers bureau: Roche, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Carlo Salvarani: None declared, Robert Spiera Grant/research support from: Roche-Genetech, GSK, Boehringer Ingelheim, Chemocentryx, Corbus, Forbius, Sanofi, Inflarx, Consultant of: Roche-Genetech, GSK, CSL Behring, Sanofi, Janssen, Chemocentryx, Forbius, Mistubishi Tanabe, Min Bao Shareholder of: Roche, Employee of: Genentech

Summary Objective To analyze the age-related changes of the physiological hand joint architecture. Method To address this concept, healthy individuals (each 10 women and 10 men in six different age decades spanning from 21 to 80 years) were recruited through a field campaign, investigated for the absence of rheumatic diseases and other comorbidities and received high-resolution quantitative computed tomography (HR-pQCT) examination of the hand joints. Number and extent of erosions and osteophytes were quantified across the ages and different sexes. Results Bone erosions [median (Q1–Q3), 1 (0–2)] and osteophytes [2 (1–4)] were found in healthy women and men with no significant sex differences. Structural changes however accumulated with age: the overall incidence rate ratio (IRR) for the number of erosions and osteophytes per age were 1.04 (95% CI: erosions 1.03–1.06; osteophytes: 1.03–1.05). This means a 4% increase in the number of erosions and osteophytes per year. Using third decade as reference, healthy individuals in the age decades from 50 years had higher IRR for erosion numbers (sixth, seventh, eigth decade: 4.87 (2.20–11.75), 6.81 (3.08–16.46) and 6.92 (3.11–16.79)) compared to younger subjects (fourth, fifth decade: 1.80 (0.69–4.87), 1.53 (0.59–4.10)). The IRRs of osteophytes also indicate a gradual increase after the fifth decade, with IRRs of 2.32 (1.32–4.17), 4.17 (2.38–7.49) and 6.86 (3.97–12.20) for the sixth, seventh and eigth decades, respectively. Conclusions Structural changes in the hand joints of healthy individuals are age dependent. While being rare under 50 years of age, erosions and osteophytes accumulate above the age of 50, suggesting that the threshold between "normal" and "pathological" is shifted with the increase of age.

We analyzed volumetric bone mineral density (vBMD) and bone microstructure using HR-pQCT in subjects with normouricemia (NU) and subjects with hyperuricemia (HU) with and without psoriasis (PSO). HU was associated with higher cortical vBMD and thickness. Differences in average and trabecular vBMD were found between patients with PSO + HU and NU. Hyperuricemia (HU) and gout are co-conditions of psoriasis and psoriatic arthritis. Current data suggest a positive association between HU and areal bone mineral density (BMD) and a negative influence of psoriasis on local bone, even in the absence of arthritis. However, the influence of the combination of HU and psoriasis on bone is still unclear. The aim of this study was to assess the impact of HU with and without psoriasis on bone microstructure and volumetric BMD (vBMD). Healthy individuals with uric acid levels within the normal range (NU), with hyperuricemia (HU), patients with hyperuricemia and psoriasis (PSO + HU), and patients with uric acid within the normal range and psoriasis (PSO + NU) were included in our study. Psoriasis patients had no current or past symptoms of arthritis. Average, trabecular, and cortical vBMD (mgHA/cm3); trabecular number (Tb.N, 1/mm) and thickness (Tb.Th, mm); inhomogeneity of the network (1/N.SD, mm); and cortical thickness (Ct.Th., mm) were carried out at the ultradistal radius using high-resolution peripheral quantitative computed tomography. In addition, bone turnover markers such as DKK-1, sclerostin, and P1NP were analyzed. In total, 130 individuals were included (44 NU participants (34% female), 50 HU (24%), 16 PSO + HU (6%), 20 PSO + NU (60%)). Subjects were aged: NU 54.5 (42.8, 62.1), HU 57.5 (18.6, 65.1), PSO + HU 52.0 (42.3, 57.8), and PSO + NU 42.5 (34.8, 56.8), respectively. After adjusting for age, sex, BMI, and diabetes, patients in the HU group revealed significantly higher values of cortical vBMD (p

ObjectiveTo assess the long-term (3 year) efficacy and safety of secukinumab in patients with active psoriatic arthritis (PsA) in the extension phase of the FUTURE 1 study (NCT01892436).MethodsFollowing the 2-year core trial, eligible patients receiving subcutaneous secukinumab 150 or 75 mg entered a 3-year extension phase. Results are presented for key efficacy and safety endpoints at week 156.ResultsIn total, 460 patients entered the extension study; 308 patients originally randomised to secukinumab were assessed for efficacy. Sustained improvements in all efficacy endpoints were achieved with secukinumab through week 156. Overall, 76.8%/54.9% (secukinumab 150 mg) and 65.2%/39.0% (secukinumab 75 mg) of patients achieved an American College of Rheumatology (ACR) 20/50 response (multiple imputation data); ACR20 responses were sustained irrespective of previous anti-tumour necrosis factor exposure. Improvements in quality of life and physical function were also sustained through week 156. Radiographic results (observed data; van der Heijde modified total Sharp score (mTSS)) showed that 78.1% (secukinumab 150 mg) and 74.8% (secukinumab 75 mg) of patients had no radiographic progression (≤0.5 increase in mTSS) through week 156. Exposure-adjusted incidence rates for selected adverse events per 100 patient-years (secukinumab 150/75 mg) were serious infections (1.7/1.6), Candida infections (1.4/0.7), Crohn’s disease (0/0.3), ulcerative colitis (0/0.3) and major adverse cardiac events (0.3/0.8).ConclusionSubcutaneous secukinumab provided sustained improvements in the signs and symptoms, quality of life and physical function of patients with active PsA with low rate of radiographic disease progression through 3 years. Secukinumab was well tolerated with no new safety signals.

Background Evaluation of actual immunopathology in psoriatic arthritis (PsA) is challenging. Current composite measures approved for PsA are very useful tools to assess disease activity in clinical routine. Nonetheless, because of subjective patients’ estimations that widely affect the scoring, in particular the distinction between remission and low disease activity is a common question of debate. Innate lymphoid cells (ILC) subsets may couple different aspects of PsA disease activity. Objectives To address whether PsA is associated with an altered composition of innate lymphoid cells and whether such changes are associated with disease activity and structural damage in PsA. Methods 124 patients satisfying the Classification Criteria for Psoriatic Arthritis (CASPAR) and 26 healthy volunteers were enrolled in the study. Information regarding clinical features, laboratory parameters were collected and disease activity score 28 (DAS28), disease activity in psoriatic arthritis (DAPSA), minimal disease activity score (MDA) were calculated. MRI and high-resolution peripheral CT were taken and PsA MRI score (PsAMRIS) was assessed. Flow cytometric analysis was performed and IFNg-producing ILC1s, IL-4/IL-5-producing ILC2s and IL-17/IL-22-producing ILC3s were identified among ILCs. Multivariate linear regression and Receiver-Operating Characteristic (ROC) Curve analysis was performed using the IBM SPSS Statistics software. Results Total number of circulating ILCs were increased in PsA patients compared to healthy controls (p Conclusions The ILC2/3 ratio correlates with various facets of PsA manifestations and might be a useful tool to evaluate disease activity in PsA patients. Disclosure of Interest None declared

Background Secukinumab has demonstrated rapid, significant and sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) in multiple Phase 3 studies.1–3 Objectives To report pooled efficacy results for secukinumab versus placebo at Week (Wk) 16 in PsA patients (pts) by previous anti-TNF therapy and with or without concomitant methotrexate (MTX) use from four Phase 3 studies: FUTURE 2, FUTURE 3, FUTURE 4 and FUTURE 5. Methods Overall, 397, 414, 341, and 996 pts with active PsA were randomised in FUTURE 2, FUTURE 3, FUTURE 4 and FUTURE 5, respectively. Secukinumab doses included subcutaneous (s.c.) 300 mg and 150 mg administered at baseline (BL) with loading doses at Wks 1, 2, and 3, followed by maintenance dose every 4 wks (q4w) starting at Wk 4 and s.c. secukinumab 150 mg administered at BL without loading dose, followed by q4w starting at Wk 4. Data collected up to Wk 16 were pooled. Assessments included ACR20/50/70, DAS-28 CRP, PASI 75/90, SF-36 PCS, HAQ-DI, and resolution of dactylitis, and enthesitis. Pooled analyses examined the effect of prior anti-TNF use (naive/inadequate response or intolerance to these agents, -IR) and with/without MTX use on clinical endpoints and are reported after application of non-responder imputation for binary variables and a mixed-effects model for repeated measures for continuous variables. Results A total of 2049 pts were included in the analysis, of which 461, 572, 335, and 681 pts received secukinumab 300 mg, 150 mg, 150 mg without load and placebo, respectively. Improvements were observed with secukinumab vs placebo for all endpoints at Wk 16 in both anti−TNF-naive and anti−TNF-IR pts and in pts with and without concomitant MTX use. Higher ACR and PASI responses and greater improvement of disease activity were observed in anti−TNF-naive pts compared to anti−TNF-IR pts. Secukinumab 300 mg provided numerically higher ACR and PASI responses compared to the 150 mg dose particularly for anti−TNF-IR pts and in pts with no concomitant MTX use. Earlier responses were observed with secukinumab with load compared to without load primarily across ACR, DAS28-CRP and PASI endpoints. Conclusions Secukinumab provided improvements in the signs and symptoms of active PsA regardless of previous anti-TNF therapy or concomitant MTX use. Higher response rates were generally observed in anti−TNF-naive pts compared to anti−TNF-IR pts. Secukinumab 300 mg was associated with higher responses compared to 150 mg particularly in anti−TNF-IR pts and in pts with no concomitant MTX use. References [1] Mease P, et al. Ann Rheum Dis. 2017;76:952–953 [2] McInnes IB, et al. Rheumatology (Oxford)2017;56:1993–2003 [3] Mease P, et al. Arthritis Rheumatol. 2017; 69 (suppl 10) Acknowledgements The study was sponsored by Novartis Pharma AG. Disclosure of Interest B. Kirkham Grant/research support from: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, Consultant for: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, Speakers bureau: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche, and UCB, P. Mease Grant/research support from: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Consultant for: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, P. Nash Grant/research support from: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, Consultant for: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, Speakers bureau: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, and Celgene, A. Balsa Grant/research support from: Pfizer, Abbvie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Consultant for: Pfizer, Abbvie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Speakers bureau: Pfizer, Abbvie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, B. Combe Consultant for: BMS, AbbVie, Janssen, Lilly, pfizer, Msd, Novartis, roche -chugai, ucb, s’angoisse, Speakers bureau: BMS, AbbVie, Janssen, Lilly, pfizer, Msd, Novartis, roche -chugai, ucb, s’angoisse, J. Rech Grant/research support from: BMS and Celgene, Speakers bureau: Abbvie, BMS, Celgene, Fresenius, Medicap, MSD, Novartis, Pfizer, and Roche, R. Martin Shareholder of: Novartis, Employee of: Novartis, G. Ligozio Shareholder of: Novartis, Employee of: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, L. Pricop Shareholder of: Novartis, Employee of: Novartis

Background T2 mapping is a non-invasive quantitative MRI approach which reflects cartilage hydration and collagen integrity without using contrast enhancement. It is a sensitive tool to determine cartilage damage and is currently spreading into broader clinical application.1 Objectives This study aimed to analyse biochemical changes in cartilage of Metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA) using T2 mapping in a 3 T MRI setting. Methods Thirty RA patients fulfilling the 2010 ACR/EULAR criteria were recruited. Image acquisition was performed using two surface coils in a 3 T MRI whole body scanner (VERIO; SIEMENS Healthcare).2 We obtained high-resolution images of the 2nd and 3rd MCP joint. T2 maps were calculated using a pixel-wise, mono-exponential, non-negative least-squares-fit analysis. Region-of-interest (ROI) analysis was performed by dividing the cartilage into medial, central and lateral phalangeal (med, cent, lat P) and metacarpal (MC) area. ACPA positive patients were compared to ACPA negative patients. Statistical evaluation was performed by means of univariate ANOVA testing with random factors. A p-value Results Fourteen ACPA positive (3 male/11 female) and 16 ACPA negative patients (6 male/10 female) were included. Mean age, sex distribution and disease duration were comparable (age: 49.0±15.1 years (ACPA+) vs. 56.1±10.9 years (ACPA-), t=1.494, p=0.146; sex distribution: χ2 (1)=0.918, p=0.338, disease duration: 7.9±7.3 years (ACPA+) vs. 3.9±3.8 years (ACPA-), U=69.0, Z=−1.799, p=0.072). T2 values were significantly higher in the majority of the ROIs in ACPA-positive (+) RA patients compared to ACPA negative (-) patients with a statistical significance in five of the six ROIs. T2 values in ms: MC med (+) 41.3±15.3 vs. (-) 29.6±7.4 p=0.010, cent (+) 43.8±14.6 vs.(-) 28.4±10.9, p=0.001, lat (+) 45.6±13.8 vs. (-) 32.0±8.6, p=0.008. P: med (+) 30.3±14.6 vs. (-) 25.7±14.0, p=0.169, cent (+) 29.9±13.0 vs. (-) 22.5±10.1, p=0.014, lat (+) 37.0±15.9 vs. (-) 28.8±12.6, p=0.039. Conclusions T2 mapping is a clinically feasible non-invasive MR tool for cartilage evaluation of RA patients‘ MC joints. ACPA positive RA patients showed significantly increased T2 values compared to ACPA negative patients reflecting a more severe cartilage alteration despite comparable disease duration. References [1] Welsch GH, Apprich S, Zbyn S, Mamisch TC, Mlynarik V, Scheffler K, Bieri O, Trattnig S: Biochemical (T2, T2* and magnetisation transfer ratio) MRI of knee cartilage: feasibility at ultra-high field (7T) compared with high field (3T) strength. European radiology2011;21(6):1136–1143. [2] Renner N, Kronke G, Rech J, Uder M, Janka R, Lauer L, Paul D, Herz B, Schlechtweg P, Hennig FF, et al. Anti-citrullinated protein antibody positivity correlates with cartilage damage and proteoglycan levels in patients with rheumatoid arthritis in the hand joints. Arthritis & rheumatology (Hoboken, NJ)2014;66(12):3283–3288. Disclosure of Interest None declared

Background Functional properties of bone in rheumatoid arthritis (RA) are still not well characterised. Objectives This study aimed to define the impact of anti-citrullinated antibodies (ACPA) on biomechanical properties in RA. Methods Based on on high-resolution peripheral quantitative computed tomography (HR-pQCT) data from the distal radius of ACPA-positive RA (RA+), ACPA-negative RA (RA-) and healthy controls (HC) micro-finite element analysis (µFEA) was carried out to measure failure load and stiffness of bone.( 1 Comparisons of µFEA parameters between groups was calculated and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength. Results A total of 276 subjects (96 RA+, 84 RA- and 96 HC) were analysed. Age and sex distributions were not significantly different between the three groups. In RA +but not in RA- failure load and stiffness were significantly decreased compared to HC (both p Conclusions In summary, µFEA showed that bone strength is significantly decreased in RA +but not in RA- disease. Reference [1] Macneil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone2008;42(6):1203–13. Disclosure of Interest None declared