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ObjectivesRisankizumab is an interleukin-23 inhibitor under study for the treatment of patients with psoriatic arthritis (PsA). The phase 3 KEEPsAKE 2 trial investigated the efficacy and safety of risankizumab versus placebo in patients with active PsA who had previous inadequate response or intolerance to ≤2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). Results through week 24 are reported here.MethodsAdults with PsA who were Bio-IR and/or csDMARD-IR were randomised to receive subcutaneously administered risankizumab 150 mg or placebo at weeks 0, 4 and 16 during a 24-week, double-blind treatment period. The primary endpoint was the proportion of patients who achieved ≥20% improvement in American College of Rheumatology score (ACR20) at week 24. Secondary endpoints assessed key domains of PsA and patient-reported outcomes.ResultsA total of 444 patients (median age 53 years, range 23–84 years) were randomised to risankizumab (n=224) or placebo (n=220); 206 patients (46.5%) were Bio-IR. At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (51.3% vs 26.5%, pConclusionTreatment with risankizumab resulted in significant improvements versus placebo in key disease outcomes and was well tolerated in patients with PsA who were Bio-IR and/or csDMARD-IR.Trial registration numberNCT03671148.

ObjectivesTo evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy.MethodsSELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts (‘non-responders’) and at week 26 based on Clinical Disease Activity Index (CDAI) >10 (‘incomplete-responders’) without washout.ResultsA total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups.ConclusionsThese observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.

Background/purposeThe manifestations of uveitis are well established in axial spondyloarthritis (ax-SpA), but not in psoriatic arthritis (PsA). We aimed to assess, in a large unselected series of PsA: (A) the frequency and clinical features of uveitis; (B) its association with PsA activity, the impact of disease and functional disability, and (C) its relationship with the biological treatment. In addition, a literature review was performed.MethodsRetrospective longitudinal study of PsA patients from a single referral hospital. PsA was classified according to the CASPAR criteria, and uveitis was diagnosed by experienced ophthalmologists.ResultsWe studied 406 patients with PsA (46.3±12.3 years). Uveitis was observed in 20 (4.9%). Uveitis was acute in all cases, anterior (80%), unilateral (80%) and recurrent (50%). Patients with uveitis had a higher prevalence of HLA-B27 (45% vs 7.5%, pThe exposure adjusted incidence rate (episodes/100 patients-year) of uveitis before versus after biological treatment decreased with anti-TNFα monoclonal antibodies (56.3 vs 9.4) and increased with etanercept (ETN) (6.03 vs 24.2) and secukinumab (SECU) (0 vs 50) (including only one patient treated in the last two cases).ConclusionThe prevalence of uveitis in patients with PsA was about 5%. The pattern was similar to that observed in ax-SpA. Uveitis was associated with a worse quality of life and greater functional disability. The uveitis exposure adjusted incidence rate decreased with anti-TNFα monoclonal antibodies and increased with ETN and SECU.

Objective The main study objective was to determine how giant cell arteritis (GCA) is diagnosed in our clinical practice and whether the EULAR recommendations have influenced the diagnostic procedures used. Methods ARTEritis of the Rheumatology Spanish Society -Sociedad Española de Reumatología (ARTESER) is a multicentre observational retrospective study conducted in 26 hospitals with support from the Spanish Society of Rheumatology. All patients diagnosed with GCA between 1 June 2013 and 29 March 2019 were included. The gold standard for the diagnosis of GCA was the judgement of the physician in charge, according to clinical criteria, supported by data available from laboratory tests, imaging studies (ultrasound, positron emission tomography (PET) and MRI/CT angiography) and temporal artery biopsy (TAB) when available. Results We included 1675 patients with GCA (mean age±SD (76.9±8.1) years, 1178women (70.3%)). Of these, 776 patients had a positive TAB (46.3%), 503 (30.0%) positive ultrasound, 245 positive PET (14.6%) and 64 positive MRI/CT angiography (3.8%). These percentages changed substantially over the study. From 2013 to 2019, the use of ultrasound in diagnosis grew from 25.8% to 52.9% and PET from 12.3% to 19.6%, while use of TAB decreased from 50.3% to 33.3%. Conclusions Biopsy was the most widely used diagnostic test for confirming GCA, but use of imaging as a diagnostic tool has grown in recent years. Following publication of the 2018 EULAR recommendations, ultrasound has displaced biopsy as the first-line diagnostic test; TAB was performed in a third and PET in a fifth of cases. Funding: Roche contributes to the financial support of this study. Acknowledgements: To the Spanish Society of Rheumatology that has promoted and provided coverage for this study. To Roche for its financial contribution that made this epidemiological study possible

We thank Wu et al for their interest in our study reporting on the prevalence of COVID-19 in patients with rheumatic diseases (RMD).1 Wu et al suggest that potential detection bias due to more frequent regular visits to hospitals in patients with RMD may explain the observed greater prevalence of hospital COVID-19 cases in these patients. However, this is highly unlikely since the identification of hospital PCR+ cases was performed in April 2020, still in the peak phase of COVID-19 pandemic in Spain, when the regular scheduled follow-up visits had been cancelled and restricted to urgent medical care. In addition, PCR test shortage resulted in the need to restrict testing to ‘COVID-19-likely’ symptomatic patients at emergency departments, making unlikely preferential testing of RMD or other specific patients. Nevertheless, we cannot exclude other biases such as greater …

Background:The efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor, in patients (pts) with active psoriatic arthritis (PsA) were demonstrated through 24 weeks in the phase 3 SELECT-PsA 1 and SELECT-PsA 2 placebo-controlled clinical trials.1,2Objectives:To describe the long-term integrated safety profile of UPA relative to adalimumab (ADA) in pts with PsA treated in the SELECT program.Methods:The SELECT-PsA program enrolled pts with prior inadequate response or intolerance to ≥1 non-biologic DMARD (SELECT-PsA 1) or ≥1 biologic DMARD (SELECT-PsA 2). Both trials include UPA 15 mg and 30 mg, and only SELECT-PsA 1 includes long-term comparison with ADA 40 mg every other week. Treatment-emergent adverse events (TEAEs: AE onset ≥first dose and ≤30 days after last dose for UPA and ≤70 days for ADA) were summarized for the following: pooled UPA 15; pooled UPA 30; and ADA. TEAEs are reported as exposure-adjusted event rates (EAERs; events/100 pts years [E/100 PY]) up to a cut-off date of 20 June 2020.Results:2257 pts received ≥1 dose of UPA 15 (N=907; 1247.2 PYs), UPA 30 (N=921; 1257.4 PYs), or ADA (N=429; 549.7 PYs), with median (max) exposures of 69 (155), 69 (154), and 68 (152) weeks, respectively. EAERs of TEAEs and serious AEs were generally similar between UPA 15 and ADA and higher with UPA 30; rates of AEs leading to study drug discontinuation were generally similar across all groups (Table 1). Similarly, rates of serious infection were comparable between UPA 15 and ADA and higher with UPA 30 (Figure 1 next page). The most common serious infection was pneumonia. Rates of herpes zoster were lower with UPA 15 than UPA 30 but higher than ADA. Most herpes zoster events involved a single dermatome; no events involved the central nervous system or other internal organs. Lower rates of opportunistic infections (OI) excluding tuberculosis were observed with UPA 15 vs UPA 30; the most common OI was mucosal candida infection. Malignancies were reported at similar rates across all treatment groups; no events of lymphoma were reported. Age-gender-adjusted standardized incidence ratios for malignancies excluding NMSC indicated no increased risk with UPA compared to the general population. Rates of adjudicated major adverse cardiovascular events and venous thromboembolic events were ≤0.3 E/100 PY for both UPA arms; all pts had ≥1 risk factor. One adjudicated gastrointestinal perforation was reported with UPA 15.Table 1.Overall Treatment-emergent AEs for Upadacitinib and Adalimumab (E/100 PY [95% CI])UPA 15 mg QDN=907(1247.2 PY)UPA 30 mg QDN=921(1257.4 PY)ADA 40 mg EOWN=429(549.7 PY)AEs263.9 (254.9, 272.9)321.5 (311.6, 331.5)286.5 (272.4, 300.7)Serious AEs10.3 (8.6, 12.1)13.2 (11.2, 15.2)9.6 (7.0, 12.2)AE leading to discontinuation6.7 (5.2, 8.1)7.8 (6.2, 9.3)7.8 (5.5, 10.2)Deathsa0.2 (-0.1, 0.4)0.2 (-0.0, 0.5)0.2 (-0.2, 0.5)aDeaths included non-treatment emergent deaths: UPA 15, 1; UPA 30, 1.ADA, adalimumab; AE, adverse event; CI, confidence interval; E, event; EOW, every other week; PY, patient years; QD, once daily; UPA, upadacitinib.Hepatic disorders were mostly transient, non-serious transaminase increases. Creatine phosphokinase elevations were reported more frequently with UPA 30 vs UPA 15; most were asymptomatic with no rhabdomyolysis reported. AEs of anemia, neutropenia, and lymphopenia were generally mild or moderate, non-serious. Except for rates of lymphopenia (higher with UPA 15), hepatic disorders, and neutropenia (both higher with ADA), lab-related TEAEs occurred at generally consistent rates between UPA 15 and ADA. Study drug discontinuation due to lab-related TEAEs was uncommon.Conclusion:The safety profiles of UPA 15 and ADA were generally similar; the rates of most AEs were higher with UPA 30 compared with ADA. Through the cut-off date, the safety profile of UPA 15 and UPA 30 in PsA pts demonstrated consistent results compared to what has been observed with UPA in rheumatoid arthritis.3References:[1]McInnes IB et al. Ann Rheum Dis, 2020; 79:12.[2]Mease PJ et al. Ann Rheum Dis, 2020.[3]Cohen SB et al. Ann Rheum Dis, 2020.Figure 1Acknowledgements:AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea, PhD of AbbVie Inc.Disclosure of Interests:Gerd Rüdiger Burmester Speakers bureau: AbbVie, Gilead, Lilly, Pfizer, Consultant of: AbbVie, Gilead, Lilly, Pfizer, Kevin Winthrop Consultant of: UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, Gilead, Galapagos, and Roche, Grant/research support from: UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, Gilead, Galapagos, and Roche, Ricardo Blanco Consultant of: Abbvie, Lilly, Novartis, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, Grant/research support from: Abbvie, MSD and Roche, Peter Nash Consultant of: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Grant/research support from: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Philippe Goupille Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Valderilio F Azevedo Consultant of: AbbVie, BMS, Pfizer, Janssen, Amgen, Novartis, Eli Lilly, UCB, Celltrion and GSK, Grant/research support from: AbbVie, BMS, Pfizer, Janssen, Amgen, Novartis, Eli Lilly, UCB, Celltrion and GSK, Carlo Salvarani Consultant of: Roche, Sanofi-Genzyme, AbbVie, Pfizer, Lilly, Novartis, Amgen, Grant/research support from: Roche, Sanofi-Genzyme, AbbVie, Pfizer, Lilly, Novartis, Amgen, Andrea Rubbert-Roth Consultant of: AbbVie, BMS, Chugai, Roche, Gilead, Janssen, Lilly, Sanofi, Amgen, Novartis, Grant/research support from: AbbVie, BMS, Chugai, Roche, Gilead, Janssen, Lilly, Sanofi, Amgen, Novartis, Elizabeth Lesser Shareholder of: AbbVie, Employee of: AbbVie, Reva McCaskill Shareholder of: AbbVie, Employee of: AbbVie, Jianzhong Liu Shareholder of: AbbVie, Employee of: AbbVie, Bosny Pierre-Louis Shareholder of: AbbVie, Employee of: AbbVie, Sandra Walko Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Apinya Lertratanakul Shareholder of: AbbVie, Employee of: AbbVie, Eric Ruderman Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, and Pfizer.

Background:Tocilizumab (TCZ) has shown promising results in the treatment of inflammatory ocular disease, especially in uveitis (1-3). Graves orbitopathy (GO) is the most common complication of Graves’ disease (GD). Conventional immunosuppressive drugs are not always effective or well tolerated. TCZ may be useful in the treatment of GO.Objectives:To assess the efficacy of TCZ in corticoid-resistant GO.Methods:Multicenter open study of corticoid-resistant GO. We measured clinical activity using the clinical activity score (CAS). CAS evaluates 10 different ocular items, ranging from 0 (no symptoms) to 10. We defined remission as the presence of CAS ≤ 3.Results:We studied 48 (95 eyes) patients (TABLE). Besides oral corticosteroids, they had received iv Methylprednisolone (n=43), methimazole (n=20), selenium (n=11) or radioactive iodine (n=5). According to the classification of severity (EUGOGO group), before of TCZ onset our patients had severe (n=19) or moderate (n=29) disease. TCZ was used in monotherapy (n=45) or combined with methotrexate (n=2) or azathioprine (n=1) at a dose of 8 mg/kg/iv/4 weeks (n=43) or 162 mg/sc/week (n=5). TCZ yielded rapid and maintained improvement and most patients achieved remission (FIGURE).TABLE:Number of patients/eyes affected, n/n48/96Age, mean (SD), years50.96 (11.78)Sex, men/women, n/n (%)10/38 (20.8 / 79.2)Regimen of TCZ therapyMonotherapy/combined treatment, n (%)45/3 (93.8/6.2)• AZA1 (2.1)• MTX2 (4.2)TCZ dosage, n (%)• 8 mg/kg/iv/4 weeks43 (89.6)• 162 mg/sc/week5 (10.4)Follow-up on TCZ therapy, mean (SD), months16.05±2.06• Remission, n (%)72 (75.8)• Discontinuation treatment, n (%)29 (60.4) • Remission25 (86.2) • Inefficacy4 (13.8) • Side effects0FIGURE:After a mean follow-up of 16.1±2.1 months, most patients experienced ocular improvement, with TCZ withdrawal in 29 cases due to remission (n=25) or inefficacy (n=4). Only 5 relevant adverse events were observed (neutropenia, external otitis, otitis media, costal osteitis and gingival hyperplasia). None of these events resulted in discontinuation of the treatment.Conclusion:TCZ appears to be an effective and safe treatment in corticoid-resistant GO.References:[1] Santos-Gómez M, et al. Clin Exp Rheumatol 2016; 34 Suppl 102(6):34-40[2] Calvo-Río V, et al. Clin Exp Rheumatol. 2014; 32 (4 Suppl 84): S54-7[3] Vegas-Revenga N et al. Am J Ophthalmol. 2019 Apr; 200:85-94.Disclosure of Interests:Lara Sanchez-Bilbao Grant/research support from: Pfizer, David Martinez-Lopez: None declared, Belén Atienza-Mateo: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Janssen and Celgene, Speakers bureau: Pfizer and Lilly, Vanesa Calvo-Río Grant/research support from: Abbvie, Lilly, UCB, MSD, Cellgene, Speakers bureau: Abbvie, Lilly, UCB, MSD, Cellgene, Rosalía Demetrio-Pablo: None declared, Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Iñigo González-Mazón: None declared, Elia Valls-Pascual Grant/research support from: Roche, Novartis, and AbbVie, Speakers bureau: AbbVie, Lilly, Pfizer, MSD, Novartis, Janssen, Bristol Myers Squibb, UCB Pharma, Beatriz Valls-Espinosa: None declared, Olga Maiz-Alonso: None declared, Ana Blanco Speakers bureau: Abbvie, Ignacio Torre-Salaberri: None declared, Verónica Rodriguez-Mendez: None declared, Ángel García-Aparicio: None declared, Raúl Veroz González: None declared, Vega Jovani: None declared, Diana Peiteado Grant/research support from: AbbVie, Lilly, MSD, and Roche, Speakers bureau: AbbVie, Roche, and MSD, Santos Castañeda: None declared, Margarita Sánchez-Orgaz: None declared, Eva Tomero Muriel: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Valvanera Pinillos: None declared, Elena Aurrecoechea: None declared, Ángel Mora: None declared, Arantxa Conesa: None declared, Manuel Fernández: None declared, J. Antonio Troyano: None declared, Marcelino Revenga: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:Although axial disease may affect up to 70% of patients (pts) with Psoriatic Arthritis (PsA), evidence on the efficacy of biologics in the treatment of axial manifestations in such pts is limited,1particularly as validated classification criteria for this subtype of PsA are not yet available. MAXIMISE (NCT02721966) is the first randomised controlled trial evaluating the efficacy of a biologic in the management of the axial manifestations of PsA and showed that secukinumab (SEC) 300 and 150 mg provided rapid and significant improvement in ASAS20 responses in these pts through week (Wk) 12.2Objectives:To present 52 wks efficacy results and imaging data from the MAXIMISE trial.Methods:This phase 3b, double-blind, placebo (PBO)-controlled, multicentre 52-wk trial included 498 pts (aged ≥18 years) with a diagnosis of PsA and classified by CASPAR criteria, spinal pain VAS score ≥ 40/100 and BASDAI score ≥ 4 despite use of at least two NSAIDs. Pts were randomised to SEC 300 mg (N=167) or SEC 150 mg (N=165) or PBO (N=166) wkly for 4 wks and every 4 wks thereafter. At Wk 12, PBO pts were re-randomised to SEC 300/150 mg. The primary endpoint was ASAS20 response with SEC 300 mg at Wk 12. The key secondary endpoint was ASAS20 response with SEC 150 mg at Wk 12. Wk 52 data are presented as observed. Bone marrow oedema of the entire spine and sacroiliac joints were assessed centrally with Berlin MRI scores at Baseline, Wk 12 and Wk 52.Results:Primary and key secondary endpoints were met; ASAS20 responses were sustained and increased further through Wk 52. 75%/79.7% of the PBO pts re-randomised at Wk 12 to SEC 300/150 mg achieved ASAS20 response at Wk 52 (Figure 1). ASAS40 responses at Wk 52 were 69.1% [SEC 300 mg], 64.5% [SEC 150 mg], 62.5% [PBO-SEC 300 mg], and 54.1% [PBO-SEC 150 mg]. At baseline, 59.5% [SEC 300 mg], 53.5% [SEC 150 mg] and 64.2% [PBO] of the pts had positive MRIs for the sacroiliac joints and/or the spine with Berlin MRI score ≥1. The reductions of Berlin MRI score for entire spine and sacroiliac joints were statistically significant for pts treated with SEC 300/150 mg vs. placebo (Figure 2a and b). There were no new or unexpected safety findings.Figure 1.ASAS20 Response over 52 Wks*Figure 2.Total Berlin MRI score for the Entire Spine and Sacroiliac Joints at Wk 12Conclusion:Secukinumab improved all evaluated ASAS responses through Wk 52 in PsA pts with axial manifestations and inadequate responses to NSAIDs and led to significant reduction of inflammatory MRI lesions in the spine and the Sacroiliac Joints. The safety profile of secukinumab through Wk 52 was consistent with previous reports.3-4References:[1]McInnes IB, et al.Lancet.2015;386(9999):1137–46.[2]Baraliakos X, et al.Arthritis Rheumatol. 2019;71 (suppl 10).[3]Langley RG, et al.N Engl J Med.2014;371:326–38.[4]Sieper J, et al.Ann Rheum Dis.2016;0:1–8.Acknowledgments:The study was sponsored by Novartis Pharma AG, Basel, Switzerland.Disclosure of Interests:Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Effie Pournara Shareholder of: Novartis, Employee of: Novartis, Sławomir Jeka Grant/research support from: AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Eli Lilly, Egis, UCB, Celgene, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Eli Lilly, Egis, UCB, Celgene, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD, Salvatore D’Angelo Consultant of: AbbVie, Biogen, BMS, Celgene, Eli Lilly, MSD, Novartis, and UCB, Speakers bureau: AbbVie, BMS, Celgene, Eli Lilly, Novartis, Pfizer, and Sanofi, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Barbara Schulz Employee of: Novartis, Michael Rissler Shareholder of: Novartis, Employee of: Novartis, Kriti Nagar Employee of: Novartis, Chiara Perella Shareholder of: Novartis, Employee of: Novartis, Laura C Coates: None declared

Background:Upadacitinib (UPA), an oral JAK inhibitor, demonstrated significant improvements in signs, symptoms, and structural inhibition as monotherapy vs methotrexate (MTX) in a randomized, controlled trial (RCT) of MTX-naive RA patients (pts) through 48 weeks (wks).1Objectives:To present the safety and effectiveness of UPA through 72 wks in an ongoing long-term extension (LTE) of the SELECT-EARLY RCT.Methods:SELECT-EARLY included 2 study periods: (1) a 48-wk double-blind, active comparator-controlled, with pts randomized to UPA monotherapy 15 or 30 mg once daily or MTX (titrated to 20 mg/wk by Wk8); (2) an LTE, up to 4 years. Pts received open-label treatment once the last pt reached Wk48. Rescue therapy was added (MTX, for UPA groups; UPA, for MTX group) to pts not achieving CDAI remission (≤2.8) at Wk26. Non-responder imputation (NRI) was used for missing data as well as for pts receiving rescue therapy. Treatment-emergent adverse events (TEAEs) are summarized per 100 pt yrs (PY) through the cut-off date of 21 Feb 2019, when all pts had reached Wk72. Data are censored at the time of MTX or UPA addition among rescued patients.Results:Of 945 pts randomized and treated, 781 (83%) completed Period 1. Of these, 775 entered the LTE, including 57 rescued pts (MTX, 33; UPA 15 mg, 17; UPA 30 mg, 7). A total of 52 (7%) pts discontinued during the LTE through the cut-off date (primary reasons: AEs [n=16, 2.1%]; consent withdrawal [n=12, 1.5%]; lost to follow-up [n=10, 1.3%]). Cumulative exposures to monotherapy with MTX, UPA 15 mg, and UPA 30 mg were 350.6, 389.5, and 383.9 PYs, respectively. Both UPA 15 mg and 30 mg as monotherapy was associated with continued statistically significant improvements in disease activity measures vs MTX monotherapy through 72 wks (Table). The safety profiles of the UPA 15 and 30 mg groups were comparable for total TEAEs and numerically higher than MTX. Serious TEAEs and TEAEs leading to discontinuation of study drug were comparable across all groups (Figure). Most AEs of special interest were comparable across MTX and UPA groups, with the exception of higher rates of herpes zoster, opportunistic infections, and elevated creatine phosphokinase among the UPA groups. Two pts receiving MTX monotherapy experienced a venous thromboembolic event, with one event reported on UPA 30 mg and none on UPA 15 mg. There were 12 deaths (including 3 non-treatment-emergent) due to varied causes.Table.Proportion of Patients at Week 72 (NRI)Parameter (%)MTXMonotherapyUPA 15 mg QDMonotherapyUPA 30 mg QDMonotherapyACR20/50/7050/39/2671***/62***/47***72***/67***/54***DAS28(CRP) ≤3.2/38/2863***/52***69***/61***CDAI ≤10/≤2.842/1960***/35***69***/44***Boolean Remission1329***33******,PMTX, methotrexate; UPA, upadacitinib; QD, once daily; ACR, American College of Rheumatology; DAS28(CRP), 28-joint disease activity index based on C-reactive protein; CDAI, clinical disease activity index.Figure.Treatment-emergent Adverse Events Through ≥72 Weeks (E/100 PYs, 95% CI).Conclusion:Long-term UPA monotherapy was associated with continued improvements in RA signs and symptoms vs MTX monotherapy through 72 wks, and only a small proportion of pts required MTX addition at Wk26. Through 72 wks of treatment, the safety profile of UPA monotherapy remained consistent with data reported through 48 wks.1References:[1]van Vollenhoven R,et al.Ann Rheum Dis2019;78(S):376.Disclosure of Interests: :Ronald van Vollenhoven Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd., Maureen Rischmueller Consultant of: Abbvie, Bristol-Meyer-Squibb, Celgene, Glaxo Smith Kline, Hospira, Janssen Cilag, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche, Mark Howard Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Alan Friedman Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB

Background:Prognosis of non-infectious refractory uveitis has improved markedly with biologic therapy (BT) (1-5). Most data are with monoclonal anti-TNF drugs, especially Adalimumab (ADA) and Infliximab (IFX). However, there is not enough evidence for the use of Certolizumab Pegol (CZP).Objectives:To evaluate the efficacy and safety of CZP in refractory uveitis secondary to Immune-Mediated Inflammatory Diseases (IMID).Methods:Multicenter study of 71 patients with uveitis due to IMID refractory to glucocorticoids and conventional immunosuppressants. Efficacy was assessed with the following ocular parameters: best corrected visual acuity (BCVA), anterior chamber cells, vitritis, macular thickness and presence of retinal vasculitis. These outcomes were compared between baseline, 1st week, 1st and 6th month, and 1st and 2nd year. Statistical analysis was performed with IBM SPSS Statistics v.23.Results:71 patients/100 affected eyes (29 men/42 women) with mean age of 40.0±11.3 years were studied. Underlying IMIDs were: spondyloarthritis (n=38), Behçet (10), psoriatic arthritis (8), Crohn disease (3), sarcoidosis (2), JIA (1), reactive arthritis (1), rheumatoid arthritis (1), relapsing polychondritis (1), TINU (1), pars planitis (1), Birdshot (1) and idiopathic uveitis (3). Uveitis pattern was anterior (n=55), posterior (6), panuveitis (6) and intermediate (4).Prior to CZP, patients had received: methotrexate (37), sulfasalazine (26), azathioprine (14), cyclosporine (10), leflunomide (3), mycophenolate mofetil (3) and cyclophosphamide (1). Previous BT was administered in 48 (67.6%) patients, with a mean of 1.4±1.3 drugs per patient as follows: ADA (n=56), IFX (27), golimumab (14), tocilizumab (5) and etanercept (3). Pregnancy was the reason for prescribing CZP in 19 patients. CZP was administered in monotherapy (n=39) or combined with conventional immunosuppressants (n=32).After a mean follow-up of 27.1±21.1 months, most of the ocular variables showed a rapid and significantly improvement (Table 1). A decrease in the median number [IQR] of flares of uveitis before and after CZP, (3 [1-4] vs. 0 [0-1], pConclusion:CZP seems to be effective and safe in patients with refractory uveitis due to IMID.References:[1]Martín-Varillas JL, et al. Ophthalmology 2018; 125:1444-1451. doi: 10.1016/j.ophtha.2018.02.020.[2]Atienza-Mateo B, et al. Arthritis Rheumatol 2019; 71:2081-2089. doi: 10.1002/art.41026.[3]Santos-Gómez M, et al. Clin Exp Rheumatol 2016; 34(6 Suppl 102):S34-S40. PMID: 27054359[4]Vegas-Revenga N, et al. Am J Ophthalmol 2019; 200:85-94. doi: 10.1016/j.ajo.2018.12.019[5]Calvo-Río V, et al. Clin Exp Rheumatol. 2014; 32 (4 Suppl 84):S54-7. PMID: 25005576Table 1.Baseline1stweek1stMonth6thMonth1styear2ndyearBCVA (mean±SD)0.68±0.270.72±0.27*0.79±0.25*0.84±0.24*0.85±0.25*0.87±0.22*Improvement in AC Cells, n (%)Patients with AC cells at baseline (n=48)-21 (43.7)30 (62.5)*41 (85.4)*48 (100)*48 (100)*Improvement in Vitritis, n (%)Patients with vitritis at baseline (n=13)-3 (23.1)8 (61.5)*11 (84.6)*13 (100)*13 (100)*OCT (µ) (mean±SD)292.5±47.7294±47.4286.7±41.9*274.7±38.7*272.8±38.9*266.31±36.2*Choroiditis; affected eyes, n, (%)3 (4.2)3 (4.2)2 (2.8)2 (2.8)1 (1.4)0 (0)Retinal Vasculitis; affected eyes, n, (%)2 (2.8)0 (0)1 (1.4)0 (0)0 (0)0 (0)*pDisclosure of Interests:None declared

BackgroundThere is significant unmet need in patients with ankylosing spondylitis (AS) who have inadequate response or intolerance to anti-tumour necrosis factor (TNF) treatment. Secukinumab, an anti-interleukin-17A monoclonal antibody, significantly improved signs and symptoms of AS in the MEASURE 2 study (NCT01649375).MethodsSubjects with active AS (N=219) received secukinumab (150 or 75 mg) or placebo at baseline, weeks 1, 2, 3 and 4, and every 4 weeks thereafter. Randomisation was stratified by prior anti-TNF use: anti-TNF-naive or inadequate response/intolerance to one anti-TNF (anti-TNF-IR). The primary endpoint was Assessment of SpondyloArthritis International Society criteria (ASAS) 20 at week 16.ResultsAt week 16, 68.2% of anti-TNF-naive subjects treated with secukinumab 150 mg achieved ASAS20 compared with 31.1% treated with placebo (pConclusionsSecukinumab 150 mg provided sustained improvements in signs and symptoms of AS in anti-TNF-naive and anti-TNF-IR subjects through 52 weeks of therapy.Trial registration numberNCT01649375.

Background:Interstitial Lung Disease (ILD) is an extra-articular complication of rheumatoid arthritis (RA) that is associated with increased morbidity and mortality. Conventional disease-modifying drugs (DMARDs) such as methotrexate (MTX) have been implicated in the development and exacerbation of a pre-existing ILD.Objectives:The aim of our study was to check the influence of combined MTX treatment in patients with RA-ILD treated with abatacept (ABA).Methods:National multicentre retrospective registry of 263 patients with RA-ILD treated with ABA. RA was diagnosed according to the ACR classification criteria of 1987 or by the EULAR/ACR criteria of 2010. ILD was diagnosed by high resolution computed tomography (HRCT). In this study we have done a subanalysis of the 46 patients treated with ABA in combination with MTX (ABA+MTX) vs. 217 patients treated with ABA in monotherapy or in combination with other synthetic DMARDs. Efficacy was evaluated according to the following parameters: a) Dyspnoea (MMRC) considering variations ≥ 1; b) Lung function test (LFT) considering variations ≥ 10% in FVC and a variation of DLCO ≥ 10%; c) Imaging test (HRCT) d) DAS28 score e) prednisone dose. Variables were collected at the beginning of the study and at months 3, 6, 12 and then every 12 months until a maximum of 60 months.Results:263 patients with ILD associated with RA were included in the study with mean age 64.64±10 years. RF or CCPA were positive in 235 (89.4%) and 233 (88.6%) cases, respectively, with a mean follow-up of 22.7±19.7 months. Baseline characteristics of both groups are shown in table 1, while data obtained during evolution of this complication are presented in Figure 1.Conclusion:Despite the baseline differences of both groups, the good evolution in the ABA+MTX subgroup suggests that this therapeutic strategy can be a safe combination for patients with RA-ILD.ABA with MTX (n=46)ABA w/t MTX (n=217)PSex (F/M)28/18122/950.625Age (years)65.11±10.216.2±9.80.202RF/CCPA + (%)91.3/91.389.8/90.10.810Smoking or past smoking (%)47.855.10.417Follow-up (months)22.73±18.0022.3±20.850.916DAS28 at baseline4.08±1.514.61±1.470.056DAS28 at last visit3.00±1.463.13±1.310.642Prednisone at baseline, median (IQR) (mg)5 (5-7.5)7.75 (5-15)0.008*Prednisone at the end of study, median (IQR) (mg)5 (1-5)5 (5-7.5)0.032*DLCO at baseline (%)66.85±19.0465.43±18.210.823DLCO at the end of study (%)66.05±20.9565.17±19.720.831FVC at baseline (%)90.06±17.7785.40±21.560.164FVC at the end of study (%)90.58±15,4584.21±21.490.038*Disclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, J. Loricera: None declared, Francisco Ortiz-Sanjuán: None declared, A. Juan-Mas: None declared, Carmen Carrasco-Cubero Speakers bureau: Janssen, MSD, AbbVie, Novartis, Bristol Myers Squibb, and Celgene, S, Rodriguéz-Muguruza: None declared, S. Rodrigez -Garcia: None declared, R. Castellanos-Moreira: None declared, RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer., CLARA AGUILERA CROS: None declared, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Sergi Ordoñez: None declared, Susana Romero-Yuste: None declared, C. Ojeda-Garcia: None declared, Manuel Moreno: None declared, Gemma Bonilla: None declared, I. Hernández-Rodriguez: None declared, Mireia Lopez Corbeto: None declared, José Luis Andréu Sánchez: None declared, Trinidad Pérez Sandoval: None declared, Alejandra López Robles: None declared, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Natalia Mena-Vázquez: None declared, C. Peralta-Ginés: None declared, ANA URRUTICOECHEA-ARANA: None declared, Luis Marcelino Arboleya Rodríguez: None declared, J. Narváez: None declared, DESEADA PALMA SANCHEZ: None declared, Olga Maiz-Alonso: None declared, J. Fernández-Leroy: None declared, I. Cabezas-Rodriguez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, A. Ruibal-Escribano: None declared, JR De Dios-Jiménez Aberásturi: None declared, Paloma Vela-Casasempere: None declared, C. González-Montagut Gómez: None declared, J M Blanco: None declared, Noelia Alvarez-Rivas: None declared, N. Del-Val: None declared, M. Rodíguez-Gómez: None declared, Eva Salgado-Pérez: None declared, Carlos Fernández-López: None declared, E.C. Cervantes Pérez: None declared, A. Devicente-DelMas: None declared, Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, Cristina Hidalgo: None declared, Sabela Fernández: None declared, Edilia García-Fernández: None declared, R. López-Sánchez: None declared, S. Castro: None declared, P. Morales-Garrido: None declared, Andrea García-Valle: None declared, Rosa Expósito: None declared, L. Exposito-Perez: None declared, Lorena Pérez Albaladejo: None declared, Ángel García-Aparicio: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD

Background:Interstitial Lung Disease (ILD) is a severe complication of Rheumatoid Arthritis (RA). Several conventional disease-modifying anti-rheumatic drugs (cDMARDs) and biologic (b) DMARDs may induce or impaired ILD-RA. Abatacept (ABA) may be useful in ILD-RA (1).Objectives:To assess the efficacy and safety of ABA in a large series of ILD-RA for a long-term follow-up.Methods:Multicenter open-level study of ILD-RA treated with at least 1 dose of ABA. ILD was diagnosed by high-resolution computed tomography (HRTC). We study these outcomes: a) 1-point change Modied Medical Research Council (MMRC); b) forced vital capacity (FVC) and/or DLCO improvement or decline ≥10%; c) change in HRCT, d) change in DAS28. e) Prednisone dose. Values were collected at 0, 3, 6, 12 and then every 12 months.Results:We studied 263 patients (150 women/113 men) (mean age;64.6±10 years), with ILD-RA. At ABA-onset they were smokers or exsmoker (53.8%), positive APCC (88.6%), median [IQR] duration of ILD of 12 [3-41.25] months, mean DLCO (65.7±18.3) and FVC (85.9±21.8).The ILD-pattern were usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%).ABA was prescribed at standard subcutaneous (125 mg/w) in 196 (74.5%) or intravenously (10 mg/kg/4 w) in 67 (25.5%); in monotherapy (n=111) or combined with cDMARDs (n=152); especially leflunomide (n=55), MTX (n=46), or antimarials (n=21).After a mean follow-up of 22.7±19.7 months most outcomes remain stable (Figure). Moreover, DAS28 improved from 4.5±1.5 to 3.1±1.3; prednisone dose reduced from a median 7.5 [5-10] to 5 mg [5-7.5] and retention rate was 76.4%. The main adverse effects were serious infections (n=28), neoplasia (n=3), serious infusion reaction (n=1) and myocardial infarction (n=1).Conclusion:ABA seems effective and relatively safe in ILD-RA.References:[1]Fernández-Díaz C et al. Semin Arthritis Rheum. 2018; 48:22-27Disclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, J. Loricera: None declared, Francisco Ortiz-Sanjuán: None declared, A. Juan-Mas: None declared, Carmen Carrasco-Cubero Speakers bureau: Janssen, MSD, AbbVie, Novartis, Bristol Myers Squibb, and Celgene, S, Rodriguéz-Muguruza: None declared, S. Rodrigez -Garcia: None declared, R. Castellanos-Moreira: None declared, RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer.CLARA AGUILERA CROS: None declared, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Sergi Ordoñez: None declared, Susana Romero-Yuste: None declared, C. Ojeda-Garcia: None declared, Manuel Moreno: None declared, Gemma Bonilla: None declared, I. Hernández-Rodriguez: None declared, Mireia Lopez Corbeto: None declared, José Luis Andréu Sánchez: None declared, Trinidad Pérez Sandoval: None declared, Alejandra López Robles: None declared, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Natalia Mena-Vázquez: None declared, C. Peralta-Ginés: None declared, ANA URRUTICOECHEA-ARANA: None declared, Luis Marcelino Arboleya Rodríguez: None declared, J. Narváez: None declared, DESEADA PALMA SANCHEZ: None declared, Olga Maiz-Alonso: None declared, J. Fernández-Leroy: None declared, I. Cabezas-Rodriguez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, A. Ruibal-Escribano: None declared, JR De Dios-Jiménez Aberásturi: None declared, Paloma Vela-Casasempere: None declared, C. González-Montagut Gómez: None declared, J M Blanco: None declared, Noelia Alvarez-Rivas: None declared, N. Del-Val: None declared, M. Rodíguez-Gómez: None declared, Eva Salgado-Pérez: None declared, Carlos Fernández-López: None declared, E.C. Cervantes Pérez: None declared, A. Devicente-DelMas: None declared, Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, Cristina Hidalgo: None declared, Sabela Fernández: None declared, Edilia García-Fernández: None declared, R. López-Sánchez: None declared, S. Castro: None declared, P. Morales-Garrido: None declared, Andrea García-Valle: None declared, Rosa Expósito: None declared, L. Exposito-Perez: None declared, Lorena Pérez Albaladejo: None declared, Ángel García-Aparicio: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:Interstitial Lung Disease (ILD) is a severe extraarticular manifestation of rheumatoid arthritis (RA). In this line, several radiological patterns of RA-ILD have been described: i) usual interstitial pneumonia (UIP), ii) nonspecific interstitial pneumonia (NSIP), iii) obliterating bronchiolitis, iv) organized pneumonia and mixed patterns. Abatacept (ABA) could be an effective and safe option for patients with RA-ILD, although the response in the different radiological patterns is not well defined.Objectives:Our aim was to assess the response to ABA in different radiological patterns of ILD.Methods:Observational retrospective multicenter study of RA-ILD treated with ABA. ILD was diagnosed by HRCT and classified by radiological patterns in 3 different subgroups of RA-ILD: a) UIP, b) NSIP and c) “other”. ABA was used sc. or iv. at standard dose. We assessed: a) Dyspnoea (MMRC scale; significant variation ≥1); b) Respiratory function tests (significant changes ≥10% in FVC and DLCO); c) HRCT imaging; d) DAS28 e)prednisone dose.Variables were collected at months 0, 3, 6, 12 months and subsequently every 12 months until a maximum of 60 months.Results:We included 263 patients: 106 UIP, 84 NSIP and 73 others (150 women / 113 men), mean age 64.64±10 years. Total patients positive for RF or CCPA were 235 (89.4%) and 233 (88.6%), respectively. In 26 out of 263 patients, the development of ILD was closely related to the administration of sDMARDs (MTX n = 11 and LFN n = 1) or bDMARDs (ETN n = 5, ADA n = 4, CZP n = 2 and IFX n = 3). Patient characteristics are shown in table 1. Figure 1 shows the evolution of the cases with available data after a mean follow-up of 22.7±19.7 months. Mean DLCO and FVC remained stable in the 3 groups without statistically significant changes, and all the groups showed a statistically significant reduction in DAS28 and prednisone dose.Conclusion:ABA could be a good choice of treatment in patients with RA-ILD independently of the radiological pattern of ILD.Disclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, J. Loricera: None declared, Francisco Ortiz-Sanjuán: None declared, A. Juan-Mas: None declared, Carmen Carrasco-Cubero Speakers bureau: Janssen, MSD, AbbVie, Novartis, Bristol Myers Squibb, and Celgene, S, Rodriguéz-Muguruza: None declared, S. Rodrigez -Garcia: None declared, R. Castellanos-Moreira: None declared, RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer., CLARA AGUILERA CROS: None declared, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Sergi Ordoñez: None declared, Susana Romero-Yuste: None declared, C. Ojeda-Garcia: None declared, Manuel Moreno: None declared, Gemma Bonilla: None declared, I. Hernández-Rodriguez: None declared, Mireia Lopez Corbeto: None declared, José Luis Andréu Sánchez: None declared, Trinidad Pérez Sandoval: None declared, Alejandra López Robles: None declared, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Natalia Mena-Vázquez: None declared, C. Peralta-Ginés: None declared, ANA URRUTICOECHEA-ARANA: None declared, Luis Marcelino Arboleya Rodríguez: None declared, J. Narváez: None declared, DESEADA PALMA SANCHEZ: None declared, Olga Maiz-Alonso: None declared, J. Fernández-Leroy: None declared, I. Cabezas-Rodriguez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, A. Ruibal-Escribano: None declared, JR De Dios-Jiménez Aberásturi: None declared, Paloma Vela-Casasempere: None declared, C. González-Montagut Gómez: None declared, J M Blanco: None declared, Noelia Alvarez-Rivas: None declared, N. Del-Val: None declared, M. Rodíguez-Gómez: None declared, Eva Salgado-Pérez: None declared, Carlos Fernández-López: None declared, E.C. Cervantes Pérez: None declared, A. Devicente-DelMas: None declared, Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, Cristina Hidalgo: None declared, Sabela Fernández: None declared, R. López-Sánchez: None declared, Edilia García-Fernández: None declared, S. Castro: None declared, P. Morales-Garrido: None declared, Andrea García-Valle: None declared, Rosa Expósito: None declared, L. Exposito-Perez: None declared, Lorena Pérez Albaladejo: None declared, Ángel García-Aparicio: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:Infections are the most common adverse event of Tocilizumab (TCZ) in Giant Cell Arteritis (GCA). In GiACTA study(1),serious infections were observed in 7% (9.6/100 patient-years) of patients who received TCZ weekly. Randomized clinical trials (RCTs) are conducted under highly standardized design excluding some real-world patients. Therefore, adverse events may be underestimated in RCTs. In our series of real-life, serious infections occurred in 11.9% (10.6/100 patient-years)(2).Objectives:In a wide series of GCA of clinical practice treated with TCZ, we assess the frequency, type and predisposing factors of serious infections.Methods:Multicenter study of 134 patients diagnosed with GCA, all of them refractory to conventional therapy, treated with TCZ. Serious infection was considered when a life-threatening infection, fatal, or requiring hospitalization occurred, intravenous antibiotics were required, or the infectious process led to persistent or significant disability.Results:16 of 134 (11.9%, 10.6/100 patient-years) patients developed serious infections during follow-up. The most frequent infections were pneumonia (n=4), urinary tract infection (n=4), and facial herpes zoster (n=2). At TCZ onset, serious infections were more frequent in older patients (74.3±9.6 vs 72.9±8.7 years), with a longer GCA evolution (20 [4.3-45.6] vs 13 [5-29.3] months), with visual manifestations (43.75% vs 17.8%) and a higher dose of prednisone at TCZ onset (30.4±15.5 vs 21.1±16.1 mg/day) (TABLE). Presence of comorbidities were similar in both groups. 13 of the 16 patients who had infections received a dose of prednisone greater than 15 mg/day (16.3/100 patient-years) compared to 3 patients under treatment with less than 15 mg/day of prednisone (4.2/100 patient-years).Conclusion:The age, GCA duration, ocular involvement and the dose of glucocorticoids, at TCZ onset, seem to be predisposing factors related to an increased risk of developing serious infections in GCA patients.References:[1]Stone JH, et al. N Engl J Med. 2017; 377:317-28.[2]Calderón-Goercke M et al. Semin Arthritis Rheum 2019 Aug;49(1): 126-135.TABLESERIOUS INFECTIONS(n=16)WITHOUT SERIOUS INFECTIONS(n=118)pBASAL FEATURES AT TCZ ONSETGENERAL FEATURES Age, years, mean± SD74.3±9.672.9±8.70.552 Sex, female/male n(%)13/388/300.760 Time from GCA diagnosis to TCZ onset (months), median [IQR]20[4.3-45.6]13[5-29.3]0.604COMORBIDITIES Hypertension, n(%)9(56)86(73)0.551 Diabetes, n(%)3(19)39(33)0.677 Chronic kidney disease, n(%)3(19)27(23)0.512CLINICAL FEATURES OF GCA PMR, n(%)9(56.25)64(54.2)0.879 Aortitis, n(%)5(31.25)53(45)0.301 Visual manifestations, n(%)7(43.75)21(17.8)0.017CORTICOSTEROIDS AT TCZ ONSET Prednisone dose mg/d, mean (SD)30.4±15.521.1±16.10.031Disclosure of Interests:Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, Elena Becerra-Fernández: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Águeda Prior-Español: None declared, E. Galindez: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Eva Salgado-Pérez: None declared, Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Susana Romero-Yuste: None declared, J. Narváez: None declared, Catalina Gomez-Arango: None declared, Eva Perez-Pampín: None declared, Rafael Melero: None declared, Francisca Sivera: None declared, Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Alejandro Olive: None declared, María Álvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernández-López: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Beatriz Arca: None declared, Roser Solans-Laqué: None declared, Arantxa Conesa: None declared, Carlos Vázquez: None declared, Jose Andrés Román-Ivorra: None declared, Pau Lluch: None declared, Paloma Vela-Casasempere: None declared, Carmen Torres-Martín: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Carmen Ordas-Calvo: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Nagore Fernández-Llanio: None declared, Antonio García: None declared, Carmen González-Vela: None declared, Javier García-Fernández: None declared, Patricia Vicente-Gómez: None declared, Ángel García-Manzanares: None declared, Norberto Ortego: None declared, Francisco Ortiz-Sanjuán: None declared, Montserrat Corteguera: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

To determine the ability of Coronary Artery Calcification Score (CACS) and carotid ultrasonography in detecting subclinical atherosclerosis in rheumatoid arthritis (RA).A set of 104 consecutive RA patients without history of cardiovascular (CV) events were studied to determine CACS, carotid intima-media thickness (cIMT) and plaques. Systematic Coronary Risk Evaluation (SCORE) modified according to the EULAR recommendations (mSCORE) was also assessed.The mean disease duration was 10.8 years, 72.1% had rheumatoid factor and/or anti-CCP positivity and 16.4% extra-articular manifestations. Nine were excluded because they had type 2 diabetes mellitus or chronic kidney disease. CV risk was categorised in the remaining 95 RA patients according to the mSCORE as follows: low (n=21), moderate (n=60) and high/very high risk (n=14). Most patients with low mSCORE (16/21; 76.2%) had normal CACS (zero), and none of them CACS100. However, a high number of patients with carotid plaques was disclosed in the groups with CACS 0 (23/40; 57.5%) or CACS 1-100 (29/38; 76.3%). 72 (75.8%) of the 95 patients fulfilled definitions for high/very high CV as they had an mSCORE ≥5% or mSCORE5% plus one of the following findings: severe carotid ultrasonography findings (cIMT0.9 mm and/or plaques) or CACS100. A CACS100 showed sensitivity similar to mSCORE (23.6% vs 19.4%). In contrast, the presence of severe carotid ultrasonography findings allowed identifying most patients who met definitions for high/very high CV risk (70/72; sensitivity 97.2% (95% CI 90.3 to 99.7)).Carotid ultrasonography is more sensitive than CACS for the detection of subclinical atherosclerosis in RA.

Objective To investigate the expression and function of the Toll-like receptor (TLR) family in peripheral blood mononuclear cells (PBMCs) of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Methods The authors analysed 70 patients with PMR, 20 with GCA, and 24 healthy controls (HC). TLR expression was assessed by flow cytometry. TLR function was assessed by stimulating PBMCs with specific ligands. Results A significantly increased expression of TLR7 in PBMCs of patients with active disease compared with HC was found. Despite increased expression of TLR7, circulating monocytes from patients showed a significantly lower in vitro response to TLR7 agonists. No amino acid substitutions predicted to be functionally damaging were found in TLR7. A normal response to specific TLR7 agonists in patients in complete remission eliminated a genetic defect. TLR expression and function were also affected to some degree in other diseases characterised by a strong acute phase response. Conclusion These data suggest activation of TLR7 during the active phase of PMR and GCA which resolves with complete disease remission. Whether this finding is the consequence of the marked inflammatory process in these disorders or activation by natural ligands remains to be explored.

Increased cardiovascular (CV) mortality due to accelerated atherosclerosis occurs in ankylosing spondylitis (AS) patients.1 ,2 Beneficial effects of antitumour necrosis factor (anti-TNF)-α agents on disease activity and endothelial cell activation were reported in AS.3 ,4 Dramatic reduction of insulin resistance (IR) and improvement of insulin sensitivity after infliximab administration were also described in non-diabetic AS patients.5 We aimed to assess, for the first time, whether infliximab administration in AS patients may alter levels of retinol-binding protein 4 (RBP-4), a protein released from adipocytes, considered as an emerging cardiometabolic risk factor, which correlates with IR in individuals with obesity, impaired glucose tolerance or type 2 diabetes, and in non-obese subjects with or without family history of type 2 diabetes.6–⇓8 RBP-4 serum levels were measured by ELISA (Phoenix Pharmaceuticals, EK-028-28) in 30 consecutive non-diabetic and mostly non-obese AS patients without history of CV events before and after an infliximab infusion. Local institutional committee approval and patients’ informed consent were obtained. Information on blood sample determinations in this cohort was previously reported.9 Infliximab was given as an intravenous infusion in saline solution over 120 min.5 Measurements were made in …

Objective:To characterise the circulating cytokine profile and the cellular source of circulating cytokines in polymyalgia rheumatica (PMR).Methods:The study included 34 patients with active untreated PMR and 17 age-matched healthy controls (HC). Circulating cytokines were measured by cytometric bead array and ELISA. Intracellular cytokines were assessed in CD3+ and CD14+ cells by flow cytometry. Cytokines in cell culture supernatants were also determined after polyclonal stimulation of patients’ peripheral blood mononuclear cells.Results:Circulating levels of interleukin-6 (IL6) were significantly higher in subjects with active PMR than in HC. Corticosteroid (CS) treatment was followed by a decrease in the level of IL6. Intracellular cytokine staining showed that circulating monocytes did not produce higher amounts of proinflammatory cytokines in patients with PMR than in HC. There was a discordance between serum levels and cytokine-producing monocyte and T cells, and it was not possible to demonstrate a Th1 bias in the peripheral compartment.Conclusions:Active PMR is characterised by increased serum levels of IL6, but not of other proinflammatory cytokines, that are rapidly suppressed by CS treatment. As circulating monocytes do not show increased production of proinflammatory cytokines, IL6 may be mainly produced in the inflamed tissue. A study of the circulating cytokine profile and its cellular source may provide a clue to new therapeutic options.

Recent studies have focused attention on the involvement of NLRP1 to confer susceptibility for extended autoimmune/inflammatory disorders, being considered a common risk factor in autoimmunity.1–3 NLRP1 provides a scaffold for the assembly of the inflammasome that activates caspases 1 and 5, required for processing and activation of the proinflammatory cytokines interleukin 1β (IL-1β), IL-18 and IL-33 and promoting inflammation.4 In this study, we examined for the first time whether NLRP1 is associated with giant cell arteritis (GCA), a chronic systemic vasculitis affecting large and medium-sized arteries derived from the aorta, in particular the cranial branches of the carotid artery. GCA is the most common vasculitis in the elderly in Western countries with a female predominance.5 To investigate the possible genetic association of NLRP1 with this disease, we genotyped a single-nucleotide polymorphism (rs8182352), which has been reported to confer risk to the development of autoimmune processes in previous studies,1 ,2 in a total of 3583 individuals, comprising a discovery set from Spain (574 patients diagnosed with biopsy-proven GCA and 2366 healthy controls) and a replication set of subjects from Italy (111 biopsy-proven GCA patients and 532 controls) using a predesigned TaqMan allele discrimination assay. All individuals were of …

Background Vogt-Koyanagi-Harada disease is a multisystem autoimmune disorder mediated by T-cells directed against antigens of tissues that contain melanin. Clinically it9s characterized by diffuse bilateral granulomatous panuveitis. Although conventional immunosuppresive therapy such as cyclosporine (CsA), azathioprine (AZA) or methotrexate (MTX) the disease can remain active and complicated by blindness. Objectives Our aim was to review the cases of VKH syndrome uveitis in a reference unit for the past five years especially those patients with anti-TNFα therapy. Methods We reviewed all the cases of posterior uveitis or panuveitis in a reference unit between January 2010 to December 2015. VKH syndrome was diagnosed by international standard criteria (1). The treatment was reviewed particularly those with anti-TNFa therapy refractory to conventional immunosuppresives. In addition we reviewed the literature of anti-TNF α therapy in a VKH uveitis syndrome Results 104 were assessed. 5 cases (4 wome /1 man) met criteria VKH syndrome, mean age was 45 years. In all cases the initial treatment was high doses of corticosteroids and conventional immunosuppressive therapy CyA (4 cases), AZA (2 Cases) CsA + AZA (2 cases). In two patients with failure to AZA + CsA, infliximab (IFX) was prescribed Weeks 0, 2 and 6 and each 8 weeks. In both cases (intorelancy and ineffectiveness to infliximab), “switch” to adalimumab 40 mg/sc biweekly achieving an adequate clinical response and remission of uveitis. In addition to the two cases in our series in the literature review we found 9 articles related to anti-TNF α therapy in VKH syndrome (Table). We found 9 series with 25 patients (14 with ADA/11 IFX). In most of them remission of intraocular inflammation was observed, 13 patients with ADA (92.8%)/10 IFX (90.9%). There are no published cases of “Switching” between anti-TNF agents in VKH. Conclusions In VKH syndrome uveitis refractory to conventional immunosuppressive, anti-TNF therapy may be a treatment option. In cases of inadequate response to the first anti-TNFa “switching” to another anti-TNFa is an option, however, these preliminary data should be tested in randomized prospective studies with larger numbers of patients. References Autoimmunity reviews. 2013; 12: 1033–1038. Rest of references in the table (2–10), Disclosure of Interest None declared

Background Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease with heterogeneous clinical manifestations. Recent studies have suggested the existence of a genetic basis for the diverse SLE clinical phenotypes. Also, there is increasing evidence indicating that a substantial part of the genetic variation associated with complex diseases is explained by small-effect genes from common genetic pathways. Objectives The objective of the present study was to identify new genetic variation associated with SLE phenotypes using a genome-wide association study at the pathway level. Methods A total of 598,258 SNPs were genotyped in a discovery cohort of n=482 SLE patients of southern European ancestry using the Illumina platform Quad610. After quality control analysis, including ancestry estimation using principal-component analysis, genome-wide pathway analysis was performed. A total of 14 clinically relevant SLE phenotypes were tested for association with n>700 reference genetic pathways. Significantly associated pathways (corrected P-value in silico analysis on cell types of relevance in SLE pathogenesis. Results In the discovery stage, two genetic pathways were significantly associated with the presence of oral ulcers and antinuclear antibodies in SLE ( P FDR VEGF ) genetic pathway ( P =1.3e-2). Analyzing the transcriptional effect of the topical immunotherapies used for the treatment of oral ulcers in SLE, we found a significant differential expression of VEGF pathway genes ( P Conclusions In this work we have performed the first genome-wide association study for clinically relevant SLE phenotype using a pathway-based approach. With this new approach, we have identified and validated the association of VEGF genetic pathway with oral ulcers in SLE. These findings represent an important step towards the characterization of the genetic basis of phenotype heterogeneity in SLE. Disclosure of Interest None declared

Objectives To determine if the use of carotid ultrasonography (US) may improve the cardiovascular (CV) risk stratification in patients with ankylosing spondylitis (AS). Methods A set of 127 consecutive patients without history of CV events, diabetes mellitus or chronic kidney disease that fulfilled definitions for AS according to the 1984 modified New York criteria were recruited to assess carotid intima-media thickness and presence of plaques. CV risk was calculated according to the systematic coronary risk evaluation (SCORE), the Framingham Risk Score (FRS) and the Reynolds Risk Score (RRS). Results Men outnumbered women (61.4%). The mean±SD age at the time of the study was 44.5±11.6 years. The median (interquartile range) delay to the diagnosis was 5 (1–12) years. HLA-B-27 was positive in 77.2%, and syndesmophytes were present in 38.9%. Carotid plaques were found in 43 (33.9%). Regardless of the algorithm used for CV risk stratification, more than 50% of the patients classified as having moderate CV risk had carotid plaques. Moreover, 20.8%, 24.6% and 53.3% of AS that fulfilled the category of low CV risk according to the total cholesterol (TC)-SCORE, FRS and RRS, respectively had carotid plaques. A model that included patients with a chart TC-SCORE ≥5% or SCORE-TC ≥1% 3 mg/L at diagnosis plus syndesmophites and carotid plaques or TC-SCORE 3 mg/L at diagnosis plus extraarticular manifestations plus carotid plaques yielded the highest sensitivity (93.0%) for high/very high CV risk in these patients. The presence of syndesmophytes was associated with increased risk of carotid plaques in AS that fulfilled definitions for low CV risk according to the TC-SCORE (OR 8.75 [95% CI 2.11 - 36.40]; p=0.002). Conclusions Our results support the use of carotid US in the assessment of CV risk in patients with AS. Disclosure of Interest None declared

Several pieces of evidence indicate that rheumatoid arthritis (RA) is a proatherogenic disease associated with increased cardiovascular (CV) death rate.1 The mechanisms leading to that are complex, including traditional CV risk factors and also the presence of a chronic inflammatory state.1 Dyslipidemia with reduction in total cholesterol and its fractions and qualitative impairment in the high density lipoprotein (HDL)-cholesterol has been observed in RA patients with active disease.2 Chronic inflammation promotes oxidative changes that alter HDL structure and reduce apolipoprotein-A-I in patients with active RA. Decreased levels of the antioxidant HDL-associated enzyme paraoxonase (PON1) have been observed in these patients.3 Improvement of inflammation, as shown in patients undergoing biologic therapy, is associated with increases of PON1 activities.4 RA is a polygenic disease. Previous studies have emphasised the implication of a genetic component in the risk of CV disease in RA.5 ,6 A functional, genetic T/C amino acid variant found within the PON1 gene (rs662) confers an amino acid change (Q192R) influential in determining PON1 activity values. …

Background Systemic Lupus Erithematosus (SLE) is a complex disease of unknown etiology, involving both genetic and environmental factors. Objectives The aim of this study was to analyze the more relevant epidemiological characteristics in a large cohort of patients with SLE and controls in the Spanish population. Methods A cross-sectional, comparative, multicenter study of patients with SLE and hypernormal healthy subjects for IMID diseases was performed. All patients were recruited through the Immune-Mediated Inflammatory Diseases Consortium (IMIDC).The IMIDC is a network of Spanish biomedical researchers focused in the study of the molecular basis of immune-mediated inflammatory diseases. All patients included in the present study were selected from the outpatient clinics of 13 Rheumatology Departments at different Spanish University Hospitals. An epidemiological questionnaire developed by experts at DNA National Bank was applied to obtain all data Results 1,070 SLE patients and 1,558 healthy subjects were included. 93% of SLE patients and 40% of controls were female. The mean age of SLE patients and controls was 45±13 years and 49±7 years respectively. In the univariate analysis, we observed that the height and weight of the control subjects was significantly higher than in patients with SLE. The level of statistical significance was decreased by introducing gender and age as covariates. Both SLE patients (55%) and control subjects (68%) mostly had secondary or higher education. The physical exercise was significantly more frequent in controls. The gender and age affect the assessment of physical activity performed by both groups of patients. Regarding employment status, most patients with SLE (35%) were housewives whereas in the control group were external employers (44%). Both SLE patients (36%) and controls (52%) most frequently use their private cars. The average consumption of tobacco, alcohol was higher in the control group but the significance level decreased in multivariate analysis, confirming the influence of gender and age on these variables. We observed a statistically significant diference on the average consumption of coffee and frequency of smoking after adjusting by confounding factors. No statistically significant differences were observed in the average number of children when comparing both groups. Conclusions In this large comparative study we describe for the first time the general epidemiological characteristics in patients with SLE and healthy subjects representative of the Spanish population. SLE patients are younger, have lower consumption of coffe/tea and smoke more often than healthy controls. The influence of gender confirms the significance level of variables such as physical activity, alcohol intake, weight and height. Disclosure of Interest None declared

Background Hypersensitivity vasculitis (HV) and Henoch-Schonlein purpura (HSP) are the most common entities included within the category of cutaneous vasculitis (CV). Palpable purpura and histological changes characterized by the presence of leukocytoclastic vasculitis are common in both conditions. Because of that, considerable overlap between them is often seen. It is especially true when the CV occurs in adults. Objectives Our aim was to assess the main clinical differences between HV and HSP in a wide and unselected series of adults with CV from a defined population. Methods We reviewed the clinical records of 297 consecutive adults (age>20years) seen at a single center between January 1975 and December 2012 that were classified as having HSP or HV according to the criteria proposed by Michel et al.1. Results Based on the inclusion criteria 102 adult patients (71 men/31 women) were classified as HSP and 195 (104 men/91 women) as HV. The mean age was similar in both groups (55.8±16.5 years in HSP and 56.8±18.3 years in HV). Precipitating events, usually an upper respiratory tract infection and/or drug intake, were more frequently observed in HV. Both at the beginning of the disease and when the CV was established clinical manifestations were more frequent in patients with HSP than in those with HV. It was the case for gastrointestinal (57.4% vs. 6.8%; p

Background The severity of clinical features and the outcome in the different series of patients with Henoch-Schonlein Purpura (HSP) shows great variability, probably due to selection-bias. Objectives Our aim was to establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center. Methods For this purpose, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed by Michel et al. 1 Results From this series of 417 patients, 240 were men and 177 women with a median age at the time of disease diagnosis of 7.5 years (interquartile range-IQR: 5.3-20.1). Three-quarters of them were children or young people 20 years old and younger (n=315) and a quarter (n=102) were adults. The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%) gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all the cases, mainly purpuric skin lesion, was the most common manifestations when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%).The main laboratory data were leukocytosis (36.7%), anemia (8.9%) and increased of serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal anti-inflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 (IQR: 2-38) months, complete recovery was observed in most cases (n=346; 83.2%) while persistent, usually mild, nephropathy was observed in 32 (7.7%) cases. Relapses were observed in almost a third of patients (n=133; 31.9%). Conclusions In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is favorable in most cases depending mostly on renal involvement. References Michel BA, Hunder GG, Bloch DA, Calabrese LH. Hypersensiviti vasculitis and Henoch-Schonlein purpura: a comparison between the two disorders. J Rheumatol. 1992; 19:721-728. Acknowledgements This study was supported by a grant from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4358

Background In 1990 The American College of Rheumatology (ACR) established criteria for the classification of vasculitis. Cutaneous vasculitis (CV) comprises a wide and heterogeneous group of entities. Objectives Our aim was to revise the usefulness of ACR-1990 criteria in classifying patients with CV. Methods Retrospective study of a wide and unselected series of patients with CV from a single university hospital from January 1976 to January 2012. Patients were classified according to the 1990 ACR methodology and criteria. Results 773 Patients (351 women/422 men) with a mean age of 34.1±27.4 years were diagnosed as having CV. Applying the 1990 ACR criteria patients were classified as secondary to connective tissue diseases (n=35), major infections (n=27), malignancies (n=16), mixed essential cryoglobulinemia (n=13), Wegener Granulomatosis (n=3), Churg-Strauss syndrome (n=3) and Polyarteritis nodosa (n=3). The remaining 673 patients were classified as Hipersensitivity vasculitis (n=247; 36.6%) or Henoch Schonlein Purpura (n=414; 61.4%). Disappointingly, 127 (18.8%) met criteria for both entities and 12 out of 673 cases did not meet criteria for HV nor HSP and were not classified. Conclusions The ACR-1990 criteria for vasculitis do not properly classify patients with CV. Acknowledgements This study was supported by a grant from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3111

Background Treatment with TCZ in combination with MTX or as monotherapy in MTX-naive patients (pts) with early RA previously demonstrated improvements in signs and symptoms and in inhibition of structural joint damage in all treatment groups at 52 wks. 1 Here, the PRO findings from the primary analysis at wk 52 of the 2-year, double-blind, placebo-controlled trial FUNCTION (WA19926) are reported, representing the effect of TCZ and/or MTX on health and functionality from the pt perspective. Objectives To assess the effect of TCZ+MTX and TCZ monotherapy vs MTX on PROs in MTX-naive pts with early RA. Methods Pts were randomized (1:1:1:1) to receive TCZ 8 mg/kg (TCZ8) + MTX, TCZ8 monotherapy, TCZ 4 mg/kg (TCZ4) + MTX, or MTX for 104 wks. Inclusion criteria included RA for ≤2 y, DAS28-ESR >3.2, MTX-naive, elevated ESR or CRP, and presence of RF or anti-CCP antibodies or radiographic erosion(s). PRO endpoints included HAQ-DI (analyzed as continuous and categorical variables), SF-36 (v2; standard 4-wk recall) Physical and Mental Component Scores (PCS, MCS), FACIT-Fatigue scores, and the ACR components Patient Global Assessment (PGA) and the Pain 100-mm Visual Analogue Scale (VAS) scores. All endpoints were analyzed as change from baseline (BL). No imputation was used for missing data. Statistical analysis of secondary endpoints followed a hierarchical chain of testing to control for type 1 error. Exploratory endpoints were not adjusted for multiplicity. 52-wk data are reported here. Results The ITT population included 1157 pts (TCZ8+MTX, n=290; TCZ8 monotherapy, n=292; TCZ4+MTX, n=288; MTX, n=287). BL characteristics were similar in all treatment groups. TCZ8+MTX demonstrated statistically significantly greater improvement in HAQ-DI scores from BL to wks 24 and 52 than were seen in the MTX group ( p =0.0011 and 0.0024, respectively; secondary endpoints, Table). Percentages of pts with the minimal clinically important difference of ≥0.22 in HAQ-DI at wk 52 were numerically higher for TCZ8+MTX than for MTX. Mean improvements in FACIT-fatigue, SF-36 PCS, SF-36 MCS, Pain VAS, and PGA VAS scores at wk 24 and wk 52 were larger for TCZ8+MTX vs MTX. Clinically relevant improvements of ≥5 for FACIT-Fatigue, >5.42 for SF-36 PCS, and >6.33 for SF-36 MCS were reached by wk 24 with TCZ8+MTX and were maintained through wk 52. Numerically higher improvements were also observed across all endpoints for TCZ4+MTX vs MTX. All PRO responses for TCZ8 monotherapy were largely similar to those seen for MTX. Conclusions These results show that in MTX-naive pts with early RA, all treatment groups showed improvement across different PROs of pain, fatigue, physical function, and quality of life. The TCZ combination therapy groups showed consistently greater numerical improvements compared to MTX alone. References Ann Rheum Dis 2013;72(Suppl 3):63. Disclosure of Interest G. Burmester Grant/research support: Abbott, BMS, Pfizer, Roche, UCB, Consultant for: Abbott, BMS, Medimmune, MSD, Pfizer, Roche, UCB, Speakers bureau: Abbott, BMS, MSD, Pfizer, Roche, UCB, R. Blanco Speakers bureau: Roche, MSD, AbbVie, Pfizer, M. Keiserman Grant/research support: Roche, BMS, Novartis, HGS, Pfizer, Consultant for: Amgen, Pfizer, Janssen, BMS, Speakers bureau: Abbott, Pfizer, Janssen, BMS, W. Rigby Consultant for: Roche, R. van Vollenhoven Grant/research support: AbbVie, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, Pfizer, Roche, UCB, Vertex, S. Dimonaco Employee of: Roche, S. Grzeschik Shareholder of: Roche, Employee of: Roche, N. Mitchell Shareholder of: Roche, Employee of: Roche DOI 10.1136/annrheumdis-2014-eular.2178

Methotrexate (MTX) is a folate antagonist with well known side effects, which mainly include haematological and hepatic adverse events, and less frequently lung or bone toxicities. The use of MTX in high doses has been associated with an osteopathy, which is characterised by severe bone pain, osteoporosis, and insufficiency fractures of the legs.1 We present two patients with rheumatoid arthritis (RA) who developed medial tibial stress syndrome (MTSS) while taking low dose MTX. The first patient, a 69 year old woman, had a history of RA diagnosed in 2001.2 After 1 year’s treatment with MTX (10 mg/week), she reported a 1 month history of severe pain in the medial part of the left tibia. The pain had an acute onset, prevented her from walking, and was relieved by …

Background Most Henoch-Schonlein Purpura (HSP) studies came from selected series and used different classification criteria Objectives Our aim was to assess the epidemiological, clinical features, treatment and prognosis in an unselected and well-defined seriesof HSP. Methods Retrospective study of a wide series of patients from two hospitals diagnosed as having HSP. Patients with vasculitis secondary to connective-tissue diseases, malignancies, severe infections, primary systemic necrotizing vasculitides, and those with other well-defined clinical conditions such as hipersensitivity vasculitis and essential myxed cryoglobulinemia were excluded from this analysis. Patients were classified as having HSP according to the criteria proposed by Michel et al [1]. Results According to the above mentioned criteria 340 patients (194 men/146 women), with a mean ±SD age of 18.7±22.6 years (range; 1 to 87) were classified as having HSP. Most of the patients (256) were young people (subset established if the disease occurred in individuals younger than 20 years) (6.9±3.1 years) and 84 were adults (54.6±17.5 years). Precipitating events were found in 41.2% of patients. A history of drug intake before the onset of vasculitis was found in 19.7% and a previous upper respiratory tract infection in 35.3%. At disease onset, the most common manifestations were skin lesions (62%), abdominal pain (19.5%), joint symptoms (11%) and fever (8.8%). When the HSP disease was diagnosed the most frequent manifestations were cutaneous (99.7%), gastrointestinal (65.6%), joint (63%), and renal involvement (41.5%). The main laboratory data were elevated ESR (31.9%), leukocytosis (32.6%), anemia (8.5%), positive rheumatoid factor (6 of 139 cases tested), positive ANA (17 of 148), C3 and/or C4 decreased (14 of 285), negative cryoglobulins (60 of 78) and negative ANCAs (35 of 35). The more frequent treatments were: NSADs (11.2%), corticosteroids (33.5%), and cytotoxic agents (5.3%) (azathioprine in 6 cases, cyclophosphamide in 6 and methotrexate in 1). After a mean follow-up of 32.9±51.2 (median, 12) months, relapses were observed in 28.5% of patients, complete recovery in 84.1%, persisted mild renal insufficiency in 4 cases and mild hematuria in 26 cases. Conclusions HSP as defined by the criteria proposed by Michel et al, represents a relatively benign syndrome that affects predominantly to young population. References Michel BA, Hunder GG, Bloch DA, Calabrese LH. Hypersensitivity vasculitis and Henoch-Schonlein purpura: a comparison between the 2 disorders. J Rheumatol. 1992 May;19(5):721-8. Disclosure of Interest None Declared

Background The prognosis of Henoch-Schonlein Purpura (HSP) is mainly related to renal involvement. Data on nephropathy in HSP are generally the result of analysis of selected populations seen in Nephrology Services. Objectives In this report we assessed the frequency and outcome of nephritis in a wide and unselected series of HSP patients. Methods Study of 142 consecutive patients classified as HSP according to the criteria proposed by Michel et al (J Rheumatol 1992; 19:721) since January 1977 to May 2012. All of them had renal involvement. Nephropathy was categorized as mild or severe. Mild nephropathy encompassed those patients with microhematuria (≥ 5 red cell/hpf) and/or proteinuria that did not reach a nephrotic syndrome range. A patient was defined as having severe nephropathy if he/she had: a) nephrotic syndrome (i.e., plasma albumin levels ≤ 25 gr/liter and either 1 gm of proteinuria/day/m 2 of body surface area in children, or > 3.5 gr of proteinuria daily in adults), with or without edema; or b) acute nephritic syndrome (i.e., hematuria with at least 2 of the following abnormalities: hypertension, increased plasma urea or creatinine levels, and oliguria). Renal insufficiency was considered if the plasma creatinine was >125% of the upper limit of normal. Results We assessed 142 HSP patients with nephritis (HSPN). At disease onset 27.4% of patients had renal involvement. During the clinical course, all of them had palpable purpura. Gastrointestinal (GI) involvement was seen in a 62% of patients. The main GI symptom was the typical colicky abdominal pain. Nausea and/or vomiting were seen in a 17.8% and melena/rectorrhagia in 32.7%. Stool guaiac test was positive in 56.8% of HSPN patients. Joint manifestations (arthralgia and/or arthritis) occurred in 61.3%. However, arthritis was only observed in 38%. Regarding nephritis, most patients had mild nephropathy. Nephrotic syndrome was found in a 12.5%, nephritic syndrome in a 6.8% and renal insufficiency in 25% of the patients. The median (IQR) amount of proteinuria (gr/24 h) was 1 (0.5-2.2) and serum creatinine (mg/dl) was 1.2 (1-2.4). Laboratory data showed leukocytosis in 22.5% and anemia in 12.7%. The mean±SD ESR was 47.1±30.2 mm/1 st hour. Serum IgA levels were increased in 60% (15 of 25 tested) of patients. Corticosteroids were given to 79.6% of HSPN patients and cytotoxic drugs to 19%. After a median (IQR) follow-up of 120.8 (110-132) months complete recovery was observed in 69.7%, persistent, usually mild, hematuria in 14.8% and chronic renal insufficiency in 4.9%. During the acute phase and throughout the complete follow-up dialysis was only required in 2.9% (4/142) of patients but none of them needed kidney transplant. The disease relapsed in 38.6% of HSPN patients. Conclusions Although renal involvement is the main prognostic factor in patients with HSP, in most cases the renal outcome is benign. Acknowledgements This study was supported by grants from “Fondo de Investigaciones Sanitarias”PI12/00193 (Spain). This work was also partially supported by RETICS Program, RD08/0075 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest None Declared

Background Henoch-Schonlein Purpura Nephritis (HSPN) and IgA Nephropathy (IgAN) have been traditionally considered related diseases Objectives To establish the possible differences and similarities between both entities. Methods Study of an unselected population of 141 patients with HSPN and 55 with IgAN from a teaching hospital. HSP was diagnosed according to the criteria proposed by Michel et al (J Rheumatol 1992). IgAN was diagnosed according to renal biopsy in 49 patients, in the remaining 6 cases biopsy was not performed due to typical clinical features. The statistical analysis was performed with the STATISTICA software (Statsoft Inc.). Continuous variables (normally and not normally distributed) were compared with the 2-tailed Student’s t-test or the Mann-Whitney U test, respectively. The chi-square test was used for the dichotomous variables. Results The mean age at onset was of 28.7±26.6 years (range; 2-84) in HSPN and 35.5±13.2 (range; 12-68) in IgAN (p=NS). Most patients in both conditions were male; 56.7% in HSPN and 63.6% in IgAN (p=NS). Precipitating events were found in 58 (41.2%) of patients with HSPN and 5 (27.3%) cases with IgAN (p= NS). The most frequent precipitating events in HSPN and IgAN were respectively drug intake (22% vs 22.5%; p NS) and an upper respiratory tract infection (34.5% vs 19.5%; p=NS). Extra-renal manifestations were more common in HSPN [skin (97.1% vs 18.6%; p

Background Cutaneous vasculitis (CV) can be a clinical manifestation of a severe infection. In such cases a delayed diagnosis or the use of immunosuppressive therapy may impair the prognosis. Objectives Our objective was to determine the frequency, subtypes of major infections and clinical characteristics of CV associated to severe infections. Methods Study of a large series of 817 unselected patients with CV seen in the same hospital. A CV was considered as secondary to infection when it was associated to a severe infection and antibiotics were needed for the resolution of the vasculitis. The diagnosis of CV required histological confirmation. Results In 27 (22 men/5 women) (mean age±SD; 52.5±17.6 years) of 817 patients (3.3%) the CV was associated to a major underlying infection: pneumonia (8 cases), endocarditis (6 cases), meningitis (4 cases), abdominal infection (3 cases), septic arthritis (2 cases), septicemia (2 cases), septic bursitis (1 case), and 1 urinary tract infection (1 case). In all cases, the vasculitic skin lesions were observed at the beginning of the clinical syndrome. The types of skin lesions were palpable purpura (26 patients) and erythematous lesions (1 case). The most common location was the lower limbs. The mean duration of skin lesions was 15±6.9 days. In addition to the specific clinical manifestation of each infection, other clinical manifestations were fever (21 patients) and constitutional syndrome (5 patients). There was not severe visceral vasculitic involvement in any case. Laboratory findings showed, leukocytosis (27 patients), elevated ESR (18 patients), anemia (16 cases), mild hematuria (8 cases), positive rheumatoid factor (6 patients), positive ANA (5 patients), decreased C3 (2 patients), and circulating cryoglobulins (3 cases). None of the 27 patients developed a connective tissue disease in the follow-up. All the patients were treated with antibiotics, and 7 required the use of low-dose corticosteroids for the resolution of the skin lesions. There was a significant delay in the diagnosis of 2 patients with endocarditis of 32 and 45 days, respectively. Two patients died due to complications of the infection, the remaining, recovered completely. Conclusions Although uncommon, CV may be a clinical manifestation of a serious infection. In this case it may be a red flag that may help the clinician to set up an early diagnosis and treatment of a severe infection. Acknowledgements This study was supported by grants from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Program, RD08/0075 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest None Declared

Background Non infectious uveitis (NIU) is frequently associated to systemic auto-immune diseases, ranging from 2% (inflammatory intestinal disease) to 40% (ankylosing spondylitis), while up to 50% of NIU are idiopathic. There is limited data on NIU burden of disease and its associated costs in Spain. Objectives The purpose of this study was to quantify the yearly costs associated to the management of NIU in Spain. Methods A systematic literature search tried to find epidemiological data and direct costs of NIU management in Spain. Information gaps were secondarily identified and filled using expert panel consensus: questionnaire consensus development on resource use items to be responded; experts’ individualized response collection; and experts’ consensus agreement on relevant resources whose costs should be calculated. Five experts, two ophthalmologists and three rheumatologists from multi-disciplinary uveitis units at tertiary hospitals, participated. All cost calculations were based on 2011 Spanish National Health System rates for procedures and drug approved prices Results From the literature search it was found that there were 9398 incident NIU cases in 2011 in Spain of which 55% were female, and 70% aged between 16 and 65 years. Acute Anterior Uveitis (AAU) showed the highest incidence (55%) followed by Posterior Uveitis (PU) and Panuveitis (PnU) (15% each), and Adult Chronic Anterior Uveitis (ACAU), Pediatric Chronic Anterior Uveitis (PCAU) and Intermediate Uveitis (IU) (5% each). Table 1 shows total associated costs per type of resource used, according to the type of uveitis. Initial drug treatment was associated to the highest cost and included topical cyclopegics, midriatics and steroids, systemic steroids, sulfasalazine, antimetabolites, T-cell inhibitors and TNF-alpha inhibitors. The second highest cost resource was surgical procedures, including cataract, glaucoma treatment, iridotomy and vitrectomy. It also shows total associated costs per patient and per type of NIU. PnU, PU, and AAU management were associated to the highest associated costs. Conclusions Clinical management of incident NIU in Spain is associated to high yearly costs of resources, mainly originated from initial drug treatment, surgical treatment of complications and diagnostic visits. Prevention of NIU could potentially originate savings to the National Health System Disclosure of Interest None Declared

Objectives To assess the efficacy of Infliximab (IFX) and adalimumab (ADA) in refractory uveitis of Behcet’s syndrome. Methods Study of 63 patients followed in the Uveitis Clinic of 24 hospitals. All of them were refractory to conventional therapy with systemic steroids and ≥1 immunosuppressive drug. Efficacy was evaluated according to SUN criteria, and macular thickness by optical coherence tomography (OCT). Outcomes and comparisons were made at week 1, week 2, month 1, month 6 and at 1 and 2 years. Statistical analyses were performed using the STATISTICA (Statsoft). Results were expressed: mean±1SD (normally distributed variables) or median [25th-75th interquartile range-IQR] (not normally). Continuous variables were compared with the Wilcoxon test. Results We studied 63 patients/110 affected eyes (36M, 27W), mean age 38.9±9.0 years. Prior to anti-TNF, patients had received ivMprednisolone (n=20), cyclosporine (CyA) (n=53), methotrexate (MTX) (n=31) and azathioprine (AZA) (n=30). IFX was the anti-TNF more commonly used (64%). The remaining patients (36%) were treated with ADA. 14 patients (22%) required switching (12 from IFX→ADA; 2 ADA→IFX). Dosage: IFX 5 mg/kg/iv every 4-8 weeks or ADA 40 mgsc/2weeks. The median[IQR] follow-up from the onset of anti-TNF was 36 [20-60] months. Significant improvement of Visual acuity (VA), Tyndall and vitritis was observed soon (week 1). At 2 years,VA improved from 0.5±0.3 at basal to 0.7±0.3 (p Conclusions Monoclonal anti-TNF therapy is effective and relatively safe in uveitis of Behcet’s syndrome refractory to conventional therapy. Disclosure of Interest None Declared