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Background The frequency and characteristics of patients with Palindromic Rheumatism (PR) (transient acute attacks of articular inflammation) prior to early rheumatoid arthritis (ERA) are unknown. Objectives To compare ERA patients who did versus did not report a history of transient episodes of joint inflammation preceding RA diagnosis. Methods Study participants were patients with ERA or suspected RA (symptoms Results 154 ERA patients were included; 66% were female and mean (sd) age was 54 (15) years. 54% had previous joint pain and swelling prior to their current episode; 42% endorsed prior episodic joint pain and swelling, approximately half of whom (20% of total, N=31) reported transient joint symptoms for over six months. Patients reporting previous palindromic symptoms were more often female, seropositive, had more comorbidities, and lower swollen joints and baseline CDAI (p Conclusion Half of ERA patients self-reported transient episodes of inflammatory arthritis prior to being diagnosed with RA. They are more likely female, seropositive, with higher income and lower disease activity. Acknowledgement The CATCH study was designed and implemented by the investigators and financially supported through unrestricted research grants from: Amgen and Pfizer Canada - Founding sponsors since January 2007; AbbVie Corporation since 2011; Medexus Inc. since 2013; Eli Lilly Canada since 2016 and Merck Canada since 2017. Previously funded by Hoffmann-LaRoche and Janssen Biotech from 2011-2016,UCB Canada and Bristol-Myers Squibb Canada from 2011-2018, and Sanofi Genzyme from 2016-2017. Disclosure of Interests Leah Ellingwood: None declared, Orit Schieir: None declared, Marie-France Valois: None declared, Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie, Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Carol Hitchon: None declared, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Glen Hazlewood: None declared, Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Diane Tin: None declared, Carter Thorne Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Janet Pope Consultant for: Eli Lilly and Company

Background Immune checkpoint inhibitors (CI) have revolutionized cancer management, but can also cause immune-related adverse events. Five percent of CI-treated patients develop inflammatory arthritis, but it is poorly defined phenotypically and immunologically. Objectives To characterize phenotypes of CI-associated arthritis, and compare cytokine levels in these patients to rheumatoid arthritis (RA) and osteoarthritis (OA) controls. Methods Patients referred for CI-associated arthralgia or arthritis were prospectively enrolled in an institutional registry. Serum was collected when patients underwent phlebotomy for a clinical indication. We used a Luminex Human Magnetic Assay to measure levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12, IL-17, IL-22, TNF, IFN-γ, PD-L1, CCL2, CXCL2, CXCL13, OSM, CCL20, GM-CSF, CXCL-11 in CI-treated patients, and in stored serum from 7 RA patients (matched for medication, age, sex, CDAI) and 4 OA patients (age, sex matched). All comparisons were planned a priori. Results Thirty-six patients were enrolled 5/1/18-1/25/19. Median [IQR] age was 67[58-78], 18(50%) were female, 14(39%) were smokers and 13(36%) had melanoma. Twenty-two (61%) were on anti-PD1 or PD-L1 monotherapy, and the remainder were on combination CI. Phenotypes included 1. Small joint involvement in 17(47%), 2. Exclusively large joint involvement in 6(17%), 3. Arthralgia without arthritis in 9(25%), and 4. Polymyalgia rheumatica in 4(11%). In all, 7(19%) had concomitant tenosynovitis or enthesitis, mostly accompanying large joint arthritis or arthralgia (6/7). Median CDAI at entry was 11[7-23] and median ESR 29[18-44]. The majority (58%) of patients with the small joint phenotype were RF and/or CCP positive and one had erosive disease, compared to none with the large joint phenotype. ANA positivity was common (74%) and did not vary across phenotypes. Median time of symptom onset was 4[0.8-12] months after CI initiation. Median follow up was 7[3-22] months but only 5(14%) had resolution of arthritis off medication during that period. 22(61%) required CI discontinuation, 5(14%) due to arthritis. 29(81%) required steroids including 15(42%) who required >20mg prednisone. 19(53%) required a synthetic DMARD and 5(14%) required a biologic DMARD. Of 33 patients with known cancer status, 15(45%) had a complete response, 5(15%) a partial response, 5(15%) “stable” disease, 6(18%) progression, and 2(6%) died. Cytokines were measured in 22 patients, who were similar to the cohort as a whole except for more CCP positivity (p=0.02). CI patients with the small joint phenotype had higher levels of IL-6 than RA controls (p=0.04) (Figure 1) and IL-6 levels trended higher in the small joint vs. exclusively large joint phenotype (Figure 2). The B cell chemoattractant CXCL13, a factor produced by T peripheral helper cells in RA synovium1, trended higher in the serum of CI patients (Figure 3). Other cytokine levels did not differ significantly in patients with the small joint vs. exclusively large joint phenotype, or in CI-arthritis patients vs. controls. Conclusion Half of patients with CI-arthritis present with an RA-like phenotype with small joint involvement and frequent seropositivity, and have elevated levels of IL-6 compared to RA patients. This small joint phenotype may represent an accelerated form of RA. References [1] Rao DA, et al. Nature 2017: 542(7639):110-114 Disclosure of Interests Karmela Kim Chan Grant/research support from: Roche: sponsored research agreement on stromal cells, Consultant for: GSK: consultant. (I am part of their immunology network, a group of about 8 immunologists who advise them regularly and broadly in the areas of inflammation and infection)., Gregory Vitone: None declared, Sara Shanaj: None declared, Aidan Tirpack: None declared, Jackie Finik: None declared, Laura Donlin: None declared, Deepak Rao Grant/research support from: Merck - Sponsored research project funding support, Consultant for: Janssen - Consultant Scipher Medicine - Consultant Amgen - Scientific advisory board Patent submitted on Tph cells, Caroline Benson: None declared, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Dana Orange Consultant for: Astra Zeneca and Pfizer., Michael Brenner Grant/research support from: Roche: sponsored research agreement on stromal cells (but has nothing to do with checkpoint related disease), Consultant for: GSK: consultant. (I am part of their immunology network, a group of about 8 immunologists who advise them regularly and broadly in the areas of inflammation and infection)., Susan Goodman Grant/research support from: Novartis: research support, Consultant for: Novartis, UCB, Pfizer: consulting, Anne Bass: None declared

Background Rheumatoid arthritis (RA) treatment emphasizes aggressive titration of disease-modifying antirheumatic drugs (DMARDs) with the goal of achieving disease remission. This often includes the use of multiple DMARDs in combination, which can have a significant impact on patients’ lives and add costs to the healthcare system. Objectives To describe the patterns of sustained remission and subsequent treatment reduction in usual clinical practice for patients with early RA. Methods Patients (age >18) enrolled in the Canadian early ArThritis CoHort (CATCH) between January 2007 to March 2017 were analyzed. CATCH is a prospective, observational study of patients with early inflammatory arthritis (symptoms 2.6) and those treated with at least one DMARD or biologic agent within the first three months of study enrolment. We defined sustained remission as achieving a DAS28 Results Eight hundred and thirty-seven (40%) of the 2,097 eligible patients achieved sustained remission during the study period. Of these, 60% did so within the first 18 months and 92% within the first four years (Figure 1). The mean (SD) baseline DAS28 was 5.1 (1.3), and HAQ-DI was 1.0 (0.7). At the time of remission, 80% were prescribed methotrexate (55% subcutaneously), 71% were prescribed combination therapy with other conventional synthetic DMARDs, and 13% were prescribed a biologic agent. In the year after attaining sustained remission, 327 (39%) patients reduced treatment in the following pattern (patients may have had more than one change): 250 patients (30%) reduced or stopped methotrexate, 196 patients (23%) reduced or stopped non-methotrexate DMARDs, and 34 patients (4%) reduced or stopped biologic agents. Of those that reduced or stopped a biologic, only one was due to side effects. For the 250 patients who reduced or stopped methotrexate, 25 were for a side effect. Conclusion Achieving sustained remission occurred in 40% of early RA patients in usual clinical practice. Treatment reductions following sustained remission occurred in over a third of patients over the next 12 months, and consisted mainly of adjustment in non-biologic DMARDs. Disclosure of Interests Maria Powell: None declared, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Orit Schieir: None declared, Janet Pope Consultant for: Eli Lilly and Company, Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie, Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, CArol Hitchon Grant/research support from: Pfizer, UCB (unrelated studies), Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Carter Thorne Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Diane Tin: None declared, Marie-France Valois: None declared, Glen Hazlewood : None declared

Background Introduction of multiple biologic DMARDs, targeted synthetic DMARDs and biosimilars has led to a paradigm shift in the management of patients (pts) with RA. There are, however, limited head-to-head studies comparing these agents to guide evidence-based treatment decisions. Abatacept versus adaliMumab comParison in bioLogic-naivE RA subjects with background MTX (AMPLE) was the first head-to-head randomised controlled trial to evaluate the efficacy of abatacept (ABA) and adalimumab. However, there are limited data replicating AMPLE findings in real-world settings. Objectives To compare effectiveness of ABA versus TNF inhibitors (TNFis) in pts with RA by line of therapy (LOT) and by LOT stratified by anti-citrullinated protein antibody (ACPA) status using data from real-world clinical practice. Methods Data from two independent RA registries comprising pts treated by physicians in routine care were used for the analysis. An RA disease-specific registry provided data on pts treated with TNFis; the other was a product-specific RA registry and provided data on pts treated with ABA.1,2 The disease-specific registry was a US-based single-centre registry; the product-specific registry was a multi-centre, 12-country registry excluding the US. Frequency matching on age (in years [yrs]; ±4 yrs’ window), RA disease duration (in yrs; ±4 yrs) and baseline CDAI category (remission [≤2.8], low activity [≤10], medium activity [≤22], high activity [>22]) between TNFi and ABA pts was done for biologic-naive and -experienced pts. Descriptive statistics were used to summarise baseline demographics, disease activity measures and serostatus for both treatment groups by LOT. Disease activity in the follow-up period was measured at the 12-month mark (±6 months). Change in disease activity after 12 months was evaluated for TNFi and ABA pts by LOT, and statistical comparison using Kruskal–Wallis test was performed. The analysis was repeated for pts stratified by ACPA status. Results Data for 105 first-line and 91 second- or further-line (subsequent-line) matched pairs of TNFi and ABA pts were included in the analysis (68 first-line and 60 subsequent-line matched pairs of TNFi and ABA pts, respectively, in ACPA+ cohort; 31 first-line and 21 subsequent-line matched pairs of TNFi and ABA pts, respectively, in ACPA– cohort; Table 1). In the biologic-experienced pts, ABA (vs TNFi) had a higher reduction in CDAI score (10.2 vs 5.2, p=0.035; Table 2). In the biologic-experienced ACPA+ pts, ABA (vs TNFi) had higher reduction in disease activity (CDAI: 13.3 vs 6.2, p=0.023; Table 2; SDAI: 13.9 vs 7.0, p=0.046). No difference in disease activity was observed between the two groups among the ACPA– pts. Conclusion Real-world RA registry data further confirm findings from the AMPLE study that the overall efficacy of ABA is similar to TNFi agents in biologic-naive pts with RA. Efficacy of ABA (vs TNFis) in biologic-experienced pts is greater, and greater reductions in joint disease activity in ACPA+ ABA (vs TNFis) pts were observed. References [1] Brigham and Women’s Hospital. BRASS. https://www.brassstudy.org/. Accessed September 12, 2018. [2] Alten R, et al. RMD Open2017;3:e000538. Disclosure of Interests Evo Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Yedid Elbez Employee of: Employee of Excelya which received funding from Bristol-Myers Squibb as contract research organization., Aarti Rao Consultant for: Bristol-Myers Squibb, Yogesh Saini Consultant for: Bristol-Myers Squibb, Christine Iannaccone: None declared, Michael E. Weinblatt Shareholder of: Stock option: CanFite, Lycera, Scipher, Inmedix, Grant/research support from: Crescendo Bioscience, Bristol Myers Squibb, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, CanFite, Corrona, Crescendo, GlaxoSmithKline, Gilead, Horizon, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Scipher, Set Point, Nancy Shadick Grant/research support from: Bristol-Myers Squibb, Sanofi/Regeneron, Crescendo Biosciences, Mallinckrodt, Amgen, Consultant for: Consulting work for Bristol-Myers Squibb for under $10,000.

Background Metabolic syndrome (MetS) is common amongst gout patients. The MetS is diagnosed when a patient has at least 3 of the following 5 conditions of hyperglycemia, hypertension, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol or abdominal obesity. Little is known about the relationship between the cumulative effects of all five metabolic syndrome conditions and the risk of mortality among adult patients with gout. Metabolic Syndrome Severity Score (MetSSS) is a new clinical prediction score that employs available components (sex, age, race, systolic blood pressure, waistline circumference, high-density lipoprotein, triglycerides and fasting blood glucose). MetSSS is a validated summary score that accounts for the combined effects of all 5 metabolic features. MetSSS allows examination of associations between MetS severity and the risk of mortality. Objectives: to use the MetSSS to examine the overall associations between MetS severity and the risk of mortality related to all-causes, cardiovascular disease and diabetes amongst United States (US) gout patients. Methods Mortality-linked data for 12,101 adults aged 18 to 90 years who participated in the Third National Health and Nutrition Examination Survey (NHANES) III (1988-1994) was analyzed. Data from NHANES III were linked to national mortality records for all participants up to time of death or end of study (i.e. 23 years following initial recruitment). All 5 metabolic features were used to calculate gender-race/ethnicity specific MetSSS Z-scores in gout patients. The Z-score is the number of standard deviations from the mean a data point is and allows a continuous representation of all MetS conditions while accounting for gender-race/ethnicity disparities. Results A total of 3,381 deaths were observed, of whom 215 had gout. The prevalence of gout amongst adults was 2.59% (95% CI; 2.13%-3.05%). Moderate to high MetS severity was significantly prevalent among gout patients (47.33% vs. 21.16% no gout; P-value In a disease-specific survival model, a one-unit increase in MetSSS score was associated with a aHR 1.62 (95% CI; 1.21, 2.15) increase in heart disease related mortality among gout patients. Amongst those with gout, a one-unit increase in MetSSS score was associated with increased risks of diabetes- and hypertension- related mortalities aHR 2.53 (95% CI; 1.43, 4.62), aHR 1.73 (95% CI; 1.07, 2.79), respectively. Conclusion The Z score calculation in our study allowed a quantification of increased diabetes- and hypertension- related mortalities, all- cause and cardiovascular mortality in patients with gout. Use of the MetSSS can provide an opportunity to identify patients at highest risk influencing patients to change their lifestyle and better comply with treatment. References [1] Wiley JF, Carrington MJ. A metabolic syndrome severity score: A tool to quantify cardio-metabolic risk factors. Prev Med2016;88:189-195. [2] Thottam GE, Krasnokutsky S, Pillinger MH. Gout and metabolic syndrome: a tangled web. Curr Rheumatol Rep2017;19:60. Disclosure of Interests Naomi Schlesinger Grant/research support from: Pfizer, Consultant for: YesNovartis, Horizon Pharma, Proteo Thera, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Mohamed Elsaid: None declared, Vinod Rustgi Grant/research support from: Genfit, Consultant for: yes Allergan, Zydus, Abbvie

Background Concerns about vaccination with the seasonal flu vaccine associating with increased risk of autoimmune rheumatic disease (AIRD) activity, and anecdotal reports of the seasonal flu vaccine triggering diseases such as vasculitis are barriers to flu vaccination in this population1-2. This is despite reports of stable disease activity following flu vaccination provided disease modifying anti-rheumatic drug therapy is continued in the peri-vaccination period3. Previous studies generally include patients with stable disease activity, and as far as we are aware, a real world study evaluating the association between inactivated influenza vaccine (IIV) administration and AIRD activity has not been conducted. Objectives To examine the association between IIV administration and primary care consultation for joint pain, fatigue, rheumatoid arthritis (RA) flare, corticosteroid prescription, and incident vasculitis in people with AIRDs. Methods We undertook within-person comparisons using self-controlled case-series (SCCS). AIRD cases who received IIV and had an outcome of interest in the same influenza cycle, between 1st September of one year and 31st August of the next year, between 2006 and 2016 were ascertained within the Clinical Practice Research Datalink. The influenza cycle (1st September of one year to 31st December of the next year) was partitioned into five exposure periods (1-15 days pre-vaccination, and 0-14, 15-30, 31-60, and 61-90 days post-vaccination), with the remaining time period classified as non-exposed. Incidence rate ratios (IRRs) and 95% confidence intervals (CI) were calculated to compare the frequency of outcomes in different periods. Results Data for 14,928 AIRD cases (69% women, 80% with RA) were included. There was no association between IIV administration and primary-care consultation for RA flare, corticosteroid prescription, and vasculitis (Table 1). Vaccination associated with reduced primary-care consultation for joint pain in the 90-day post-vaccination period (IRR (95%CI) 0.91(0.87-0.94)), and fatigue (IRR (95%CI) 0.40(0.22-0.71)) in the 61-90 days post vaccination (Table 1). Conclusion The administration of IIV was not associated with flare of the underlying AIRD and its association with reduced disease activity warrants further investigation. Nevertheless, these data add to the accumulating evidence to support seasonal influenza vaccination in people with AIRDs. References [1] Loubet P, et al. Vaccine. 2015; 33(31):3703-8. [2] Birck R, et al. Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases. 2009; 15(6):289-91. [3] Park JK, et al. Annals of the Rheumatic Diseases. 2018; 77(6):898-904. Disclosure of Interests Georgina Nakafero: None declared, Matthew Grainge : None declared, Puja Myles Grant/research support from: In my previous role I have worked on a project that was funded via an unrestricted educational grant from Roche. See details including contract: https://www.nottingham.ac.uk/research/groups/healthprotection/projects/pride.aspx, Christian Mallen: None declared, Weiya Zhang Consultant for: Grunenthal for advice on gout management, Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant for: Advisory boards on gout for Grunenthal and Mallinckrodt, Jonathan Nguyen-van-tam Grant/research support from: From F. Hoffmann-La Roche. See details: https://www.nottingham.ac.uk/research/groups/healthprotection/projects/pride.aspx, Consultant for: Ad hoc paid consultancy and lecturing for several influenza vaccine manufacturers (Sanofi-Pasteur MSD, Sanofi-Pasteur, GlaxoSmithKline plc (GSK), Baxter AG, Solvay, Novartis) and manufacturers of neuraminidase inhibitors (F. Hoffmann-La Roche: oseltamivir (Tamiflu®) and GSK: zanamivir (Relenza®))., Employee of: A former employee of both SmithKline Beecham plc (now part of GSK), Roche Products Ltd. (UK), and Sanofi-Pasteur MSD, all prior to 2005), Speakers bureau: Ad hoc paid consultancy and lecturing for several influenza vaccine manufacturers (Sanofi-Pasteur MSD, Sanofi-Pasteur, GlaxoSmithKline plc (GSK), Baxter AG, Solvay, Novartis) and manufacturers of neuraminidase inhibitors (F. Hoffmann-La Roche: oseltamivir (Tamiflu®) and GSK: zanamivir (Relenza®))., Abhishek Abhishek Grant/research support from: AstraZeneca and OxfordImmunotech, Grant/research support from: AstraZeneca and Oxford Immunotech, Speakers bureau: Menarini pharmaceuticals, Speakers bureau: Menarini pharmaceuticals

Background Since the introduction of anti-TNF biosimilars in routine clinical practice, there has been a drive to implement the switch program for all biosimilars at the point of availability. Rituximab biosimilar was granted marketing authorisation by the EMA in February 2017. Our Trust was one of the first centres to embrace a CQUIN which required adoption of biosimilar within three months for new patients and one year for switchers. This could help deliver significant savings to the NHS whilst achieving similar clinical outcomes. Objectives We report our early experience of introducing rituximab biosimilar in people with RA. Methods A list of all patients prescribed rituximab was extracted through our database. A ‘switch’ letter was drafted and sent to all patients including Truxima information sheet. Patients were given the opportunity to contact nurse helpline for information or if disease control worsened/adverse effects developed. We reviewed all relevant records and collected data on any adverse events and disease outcome on either side of the switch. Patients were reviewed as originally planned by their respective clinicians. Results 44 patients with RA on 2 g dose six-monthly were identified established on rituximab. Four had stopped treatment prior to switching. All 40 agreed to switch to Truxima that was completed by February 2018. Mean age of switchers was 58.6 (range 26-80 years). Eight were men and remaining 32 (80%) were women. Fourteen (35%) were Asian, one Afro-Caribbean and the rest (62%) were White Caucasian. DAS28 scores were available for all participants. Prior to the switch median DAS28 was 3.0 (range 0.6-5.1). Following the switch it was 2.95 (range 1.5-5.7). Amongst these, eight (20%) reported adverse effects. Four had serum sickness reaction within the first week of the second dose with loss of efficacy. One required admission to ED ( Adverse events related to Rituximab biosimilar switch Conclusion Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab and etanercept. All were happy to switch after receiving a letter and having the opportunity to contact if necessary. Substantial annual cost savings of nearly £140,000 were achieved once the switch process completed. At group level there were no major differences in disease outcomes. However, 10% had severe serum sickness reaction with loss of efficacy and loss of confidence in the drug. One patient developed military TB despite having one previous originator cycle with no issues. We support the routine switching from originator to biosimilar rituximab however close monitoring is required certainly in the first few weeks of dose administration. Disclosure of Interests: Muhammad Khurram Nisar Grant/research support from: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Novartis, Celgene, Mallinckrodt, UCB and Lilly, Consultant for: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Novartis, Celgene, Mallinckrodt, UCB and Lilly, Speakers bureau: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Novartis, Celgene, Mallinckrodt, UCB and Lilly

Background RA-associated interstitial lung disease (RA-ILD) is an extra-articular manifestation of RA and is one of the leading causes of death in patients (pts) with RA.1 Previous studies have indicated that clinical factors such as age, sex, smoking and autoantibody positivity are strongly associated with RA-ILD.2 There is also evidence of active RA being related to increased risk for clinically apparent ILD.3 However, there are limited data on how pts with RA-ILD are managed for their joint conditions and joint outcomes. Objectives To evaluate RA treatment patterns in pts with subclinical and clinical RA-ILD compared with pts with RA without ILD, and to assess joint disease activity at baseline and change in disease activity by treatment in all cohorts. Methods Data from adult pts with RA enrolled in a longitudinal sequential RA registry were analysed. Pts in the registry were evaluated annually by a rheumatologist for disease activity and treatment, and semi-annually on multiple clinical patient-reported outcomes (PROs) and resource utilisation parameters. Pts with chest computed tomography (CT) scans performed to evaluate clinical indications for ILD and with blood samples were included in this analysis. Pts with chest CT scans that were indeterminate for ILD were excluded from the study. Pts were then divided into two mutually exclusive groups: non-ILD RA pts and RA-ILD pts. RA-ILD pts were further divided into subclinical and clinically evident ILD. Date of chest CT scan was considered the index date. The two cohorts were compared using descriptive statistics to summarise baseline differences in demographics, disease activity measures, serostatus and treatments. Kruskal–Wallis test for continuous variables and chi-square test for categorical variables were performed, with two-sided significance level of 0.05. Multivariable linear regression was used to evaluate change from baseline to 12 months in joint disease activity for pts with available data at baseline and follow-up. Results 75 pts with chest CT scans were included in the analysis. Of these, 38.7% (n=29) were non-ILD RA and 61.3% (n=46) had some manifestation of RA-ILD. Of the RA-ILD cohort, 63.0% (n=29) and 37.0% (n=17) were classified as subclinical and clinically evident RA-ILD, respectively. At the time of chest CT scan, RA-ILD (vs non-ILD RA) pts were older with longer disease duration, a greater proportion were male and had higher anti-citrullinated protein antibody and RF titres (Table 1). In terms of RA treatments, a significantly greater proportion of RA-ILD (vs non-ILD RA) pts were on corticosteroids (CS; 47.8% vs 20.7%) and a significantly greater proportion of clinically evident RA-ILD (vs non-ILD RA) were on non-TNF inhibitor (TNFi) biologics. RA-ILD (vs non-ILD RA) pts had numerically higher joint disease activity and modified HAQ score at baseline (Table 1). However, the change in joint disease activity and PROs in RA-ILD pts was numerically greater vs non-ILD RA pts. In a multivariable analysis, RA-ILD status did not impact change in joint disease activity, but baseline joint disease activity was significantly associated with reduction in joint disease activity at 12 months (Table 2). Conclusion RA-ILD pts compared with non-ILD RA pts in clinical practice are more likely to be managed with CS therapy and non-TNFi bDMARDs. The improvement in joint disease activity was similar between RA-ILD and non-ILD RA pts. The analysis was limited by small sample size; further studies with larger pt numbers are required to confirm the findings. References [1] Doyle JT, et al. Am J Respir Crit Care Med2015;191:1403–12. [2] Sparks JA, et al. Arthritis Care Res (Hoboken)2016;68:753–62. [3] Sparks JA, et al. Arthritis Rheumatol2018; 70(suppl 10):abstract 884. Disclosure of Interests Evo Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Tracy Doyle Grant/research support from: Receive research support from Bristol-Myers Squibb and I’m involved in a clinical trial funded by Genentech., Jeffrey Sparks Grant/research support from: Bristol-Myers Squibb, Amgen, Consultant for: Optum, Aarti Rao Consultant for: Bristol-Myers Squibb, Yogesh Saini Consultant for: Bristol-Myers Squibb, Christine Iannaccone: None declared, Michael E. Weinblatt Shareholder of: Stock option: CanFite, Lycera, Scipher, Inmedix, Grant/research support from: Crescendo Bioscience, Bristol Myers Squibb, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, CanFite, Corrona, Crescendo, GlaxoSmithKline, Gilead, Horizon, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Scipher, Set Point, Nancy Shadick Grant/research support from: Bristol-Myers Squibb, Sanofi/Regeneron, Crescendo Biosciences, Mallinckrodt, Amgen, Consultant for: Consulting work for Bristol-Myers Squibb for under $10,000.

Background Fatigue is common in early RA(ERA) and though some patients experience improvement in fatigue when disease is well controlled, others experience persistent fatigue associated with work disability, poor QOL, and depression. Objectives To compare patterns and predictors of improved vs. persistent fatigue in the first year of ERA. Methods Data were from ERA patients (symptoms Results The 1002 pts were mostly white (81%), female (71%), with a mean (SD) age of 54 (15); 32% were obese. 70% had high fatigue at baseline; these patients were more obese, had OA/backpain, poor sleep, depression, major stress, and higher disease activity (Table 1). Among those with initial high fatigue, 30% had persistent fatigue at 12 months and was associated with obesity, comorbidities, FM, longer symptom duration, and slightly lower baseline fatigue. Predictors of improved fatigue in multivariable models were BMI Conclusion Fatigue is common in ERA and associated with active disease, worse pain and disability, obesity, depression, major stressors, poor sleep and OA/backpain. In high fatigue pts, those who are not obese, have higher pain, and take ≥20 mg MTX are more likely to improve over the first year. Optimizing weight, sleep, physical and emotional health and MTX use may improve persistent fatigue beyond control of RA inflammation. Disclosure of Interests Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie, Orit Schieir: None declared, Marie-France Valois: None declared, CArol Hitchon Grant/research support from: Pfizer, UCB (unrelated studies), Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Glen Hazlewood: None declared, Carter Thorne Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Janet Pope Consultant for: Eli Lilly and Company, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Diane Tin: None declared, Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron

Background: Pain is an important issue for people with osteoarthritis (OA). Topical non-steroidal anti-inflammatory drugs (tNSAIDs) and capsaicin are recommended treatments, but reduce OA pain by different mechanisms. Objectives: To [1] determine the relative efficacy of tNSAIDs and capsaicin in OA and [2] identify predictors of response that may allow tailoring of topical therapy to the individual. Methods: Systematic literature searches were conducted up to 16/11/2015 for randomised controlled trials (RCTs) of tNSAIDs or capsaicin in OA. Placebo-controlled RCTs were pooled in conventional meta-analyses (CMA) for specific (difference between treatment and placebo) and overall (pain reduction in treatment arm) treatment effects. Bayesian network meta-analysis (NMA) compared treatments via placebo. RCT data custodians were contacted and an individual patient data meta-analysis (IPDMA) examined for predictors of response. A pilot n-of-1 trial series (PNTS) examined treatment effects, patient preferences, and predictors of response. Participants with painful radiographic knee OA were allocated to three treatment cycles, each comprising four weeks treatment with 5% ibuprofen gel and 0.025% capsaicin cream in a random order. Effect sizes (ES) are Hedges’ g and 95% confidence interval (CI) or credible interval (CrI). Predictors of response were identified in regression modelling for treatment-by-covariate interactions (specific effect) or covariate associations (overall effect). 9 and 25 predictors were examined in IPDMA and PNTS, respectively. Results: Of 63 tNSAID and 10 capsaicin RCTs identified, CMA and NMA analysed 21 tNSAID (n=6191) and five capsaicin (n=415) RCTs. The quality of evidence was moderate for tNSAIDs and very low for capsaicin. Overall treatment effects were large and likely clinically significant (tNSAIDs ES 1.23, 95%CI 1.06-1.41; capsaicin ES 1.05, 95%CI 0.52-1.57). tNSAIDs (all drugs/doses grouped) were superior to placebo (ES 0.31, 95%CI 0.20-0.41), but capsaicin was only effective at 0.025% concentration (ES 0.41, 95%CI 0.17-0.64; ES of all capsaicin RCTs 0.28, 95%CI -0.04-0.60). On average, tNSAIDs and capsaicin were equally effective (ES 0.04, 95%CrI -0.29-0.37). IPD were provided for 15 (n=3889) tNSAID RCTs, including 11 (n=3140) placebo-controlled RCTs. No IPD were obtained for capsaicin. A significant but small interaction was observed between sex and tNSAID use for pain relief, with women reporting greater effect (11 RCTs, n=2939, p=0.023). 22 participants enrolled in the PNTS and completed 104 treatment periods. Clinically important pain relief (≥1 on 0-10 numeric rating scale) was achieved in 64% of periods, with no difference in efficacy between treatments overall (p=0.271). Individual responses to treatment varied, with c.60% of people preferring one treatment over the other, but without clear predictors for the preference. Conclusion: tNSAIDs and capsaicin may relieve OA pain, but treatment effects from group comparisons do not directly translate to treatment outcomes at an individual level. No baseline characteristics robustly determine which treatment is more likely to benefit an individual. Patients may benefit from trying both treatments to determine which is better for them. Acknowledgement: M Underwood (Warwick University), A Suter (Bioforce AG/A.Vogel Produkte), GR Mautone (IBSA Institut Biochimique SA), and GSK for sharing IPD; D Burke for statistical advice; and D McWilliams for trial randomisation Disclosure of Interests: Monica Persson: None declared, Joanne Stocks Grant/research support from: Co-I on research grant from Pfizer/Eli Lilly, Aliya Sarmanova: None declared, Gwen Fernandes: None declared, Gyula Varadi Employee of: Inpellis, Inc. (previous); BioPhysics Pharma, Inc (current), Mohammad Hashem Hashempur: None declared, Robbert van Haselen Consultant for: Consultancy services for homeopathic pharmaceutical companies, David Walsh Consultant for: Pfizer, GlaxoSmithKline. Consultancies on arthritis pain, Speakers bureau: Pfizer Ltd for a talk at OARSI 2018, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant for: Advisory Boards on Grunenthal and Mallinckrodt, Weiya Zhang Consultant for: Grunenthal for advice on gout management, Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium

Background: Melanocortin receptor agonists, such as αMSH have been shown to reduce inflammation in preclinical models, suppressing the production of proinflammatory cytokines. Natural and synthetic ACTH analogues remain linked to the induction of corticosteroids as their primary mechanism of action, leading to the anti-inflammatory and immunosuppressive responses. Repository Corticotropin Injection (RCI) is a complex mixture containing purified porcine pituitary ACTH-analogue, and is an FDA-approved treatment for several inflammatory diseases. RCI has been shown to be effective in steroid-refractory autoimmune disease. Objectives: We hypothesize that Acthar has an immune regulatory response distinct from synthetic ACTH and steroids. These studies sought to explore the differences between RCI and synthetic ACTH on corticosterone levels in rats and cytokine production in a murine T cell activation model. Methods: RCI (10, 40, or 400 IU/kg) or ACTH (0.6, 1.2, or 2.4 mg/kg) was administered to Sprague Dawely rats, plasma samples collected and analyzed for corticosterone. To determine the effect on T cell cytokine production, Balb/C mice were treated with RCI (10, 40, and 400 U/kg), ACTH (0.6, 1.2, or 2.4 mg/kg) or prednisolone 1 hour prior to the administration of an anti-CD3. Two hours after antibody administration, plasma cytokines were measured using Meso Scale multiplex ELISA. Results: RCI and ACTH peak corticosterone and area under the curve (AUC) were evaluated. RCI-induced corticosterone rapidly peaked between 2 -8 hrs. and was dependent on the dose. ACTH displays a delay in the peak time (8-24 hours) and was not dose dependent. When compared to the high dose ACTH, RCI reduced the AUC by 50.0 ± 2.6%, 45.5 ± 5.6% and 27.3 ± 12.5% respectively for 10, 40, and 400 IU/kg. However, there was no significant reduction between any of the ACTH doses tested. To further explore functional differences between RCI and ACTH, we examined the effects on T cell activation. In vivo T cell activation with the anti-CD3 antibody (clone, 145-2C11) increased several cytokines, including IL-2, IL-6, IL-10, and IFNγ. Treatment with RCI, ACTH, or prednisolone significantly reduced the production of IL-2, IL-4, IFNγ, and TNFα. Interestingly, RCI showed an inverse dose-response on the production of IL-6 and IL-10. RCI inhibited the production of IL-6 at 74.7 ± 4.4% and 67.9 ± 8.5% and IL-10 at 39.1 ± 7.1% and 26.7 ± 9.3% for 10 and 40 IU/kg, respectively, whereas 400 IU/kg had no effect. ACTH inhibited the production of IL-6 at a similar level for all doses tested and had no effect on IL-10 production, whereas treatment with prednisolone inhibited all cytokines. Conclusion: These data show that RCI has a reduced steroidal response compare to synthetic ACTH. RCI has a direct and distinct immunomodulatory response on T cells unique from both synthetic ACTH and steroids. These characteristic effects suggest a mechanism of action for RCI that is steroid-independent and may help explain its benefit in steroid refractory syndromes. Disclosure of Interests: Dale Wright Shareholder of: Mallinckrodt Pharmaceuticals, Employee of: Mallinckrodt Pharmaceuticals, Ben Zweifel Shareholder of: Mallinckrodt Pharmaceuticals, Employee of: Mallinckrodt Pharmaceuticals, Prabha Sharma Shareholder of: Mallinckrodt Pharmaceuticals, Employee of: Mallinckrodt Pharmaceuticals, Karen Galen Shareholder of: Mallinckrodt Pharmaceuticals, Employee of: Mallinckrodt Pharmaceuticals, Rick Fitch Shareholder of: Mallinckrodt Pharmaceuticals, Employee of: Mallinckrodt Pharmaceuticals

Background Globally various incentive schemes have been employed in primary care to improve early diagnosis and management of several rheumatic conditions. In the UK, the Primary Care Quality and Outcomes Framework (QOF) rewards general practices for the provision of ‘quality care’ and helps to fund further improvements in the delivery of clinical care. Currently, there is one quality indicator in place for secondary prevention of osteoporosis. In order to help establish an integrated care pathway encompassing the whole patient journey between primary and secondary care, we undertook a detailed survey of two GP practices. Objectives The aims of the exercise were to identify the utility of quality indicator and any gaps in the model of care for the high-risk osteoporosis patients. Methods An independent service evaluation tool was employed to interrogate the IT system used in the GP surgeries. All patients over the age of 65 were extracted from the database and FRAX analysis was undertaken. Those with medium to high FRAX score (i.e. ten-year risk of >20% for major osteoporotic fracture and/or >5% for hip fracture) were captured to explore whether they were offered further evaluation and bone-sparing therapy as necessary. Results Of 18,248 patients registered in the multi-cultural urban practices, 6796 were >65 years old. 793 had pre-defined moderate-high FRAX score. 300 (37%) had a confirmed diagnosis of osteoporosis. Median age was 78 (range 65-103 years). 249 (83%) were women. 88.5% were White and remaining of other ethnicities. 20/300 (6.6%) had been coded to have ever sustained a fragility fracture. 178 (59.3%) were prescribed bone-sparing therapy with five people taking it for over five years. 91% were prescribed oral therapy (78% alendronic acid, 10% risedronic acid and 3% others) and remaining had parenteral therapies. Of the 27 patients not receiving any treatment, 11 (30%) were incorrectly coded. The remainder’s reasons for lack of treatment include intolerance, poor adherence and comorbidities. Conclusion This study highlights the inadequacy of quality indicators in the overall management of osteoporosis burden in primary care. It relies heavily on active identification process for high-risk individuals and correct coding of fragility fracture. However the vast majority of patients with moderate-high risk, based on case finding strategy advised by international bodies e.g. FRAX, remain hidden. Less than 10% of patients with confirmed osteoporosis fulfil the quality outcome in this survey. The QOF hence fails to reflect the nature of disease burden in the primary care thereby risking the management strategies skewed towards too small a cohort and missing the big picture. It is clear that quality indicators for osteoporosis need to be aligned to risk stratification model. This will allow better identification of at-risk individuals and improved care pathway for patients requiring bone active therapies. Disclosure of Interests Sultana Parvin: None declared, Manraj Barhey: None declared, Talib Abubacker: None declared, Muhammad Khurram Nisar Grant/research support from: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Novartis, Celgene, Mallinckrodt, UCB and Lilly, Consultant for: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Novartis, Celgene, Mallinckrodt, UCB and Lilly, Speakers bureau: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Novartis, Celgene, Mallinckrodt, UCB and Lilly

Background: RA patients may cancel scheduled visits with their rheumatologist. In clinical practice, a validated patient-reported disease activity measure that tracks well with traditional clinical indices could address an important gap by providing real-time information on RA disease activity when a visit to the rheumatologist is not possible. Objectives: To assess concordance between the 5-item patient-reported Rheumatoid Arthritis Flare Questionnaire (RA-FQ) (1,2) and the Clinical Disease Activity Index (CDAI) in patients with early RA (ERA) treated in rheumatology clinics in 2 countries with different health systems. Methods: Data were analyzed from patients enrolled in the Canadian early ArThritis CoHort (CATCH) between Nov 2011 and March 2017 and in the Consortium of early ArThritis Cohorts- USA (CATCH-US) from Dec 2014 to Dec 2018. Both observational studies had a similar design; enrolled patients diagnosed with EIA ( Results: The study included 818 Canadian and 75 American early RA patients. Age, male sex, and disease activity was higher in the Canadian cohort, while post-secondary education was higher in the US cohort (Table1). RA-FQ and CDAI scores tracked closely with one another over time in both cohorts (Canada ICC: 0.76; US ICC: 0.80) Conclusion: There was high concordance between the RA-FQ and CDAI measures over the 1st year of follow up in 2 early RA samples recruited in 2 countries. The RA-FQ may help patients and clinicians track patient disease activity between clinic visits. References: [1] Bykerk VP et al. RMD Open, 2016 [2] Bartlett SJ et al. J Rheumatol. 2017 Acknowledgement: CATCH: Amgen & pfizer-founding sponsors 2007+; abbvie 2011+; medexus 2013+; eli lilly 2016+, merck canada 2017+, hoffmann-laroche & janssen biotect 2011-2016, ucb & bms 2011-2018, sanofi-genzyme 2016-2017. catch-us: bms, ucb, genentech; cedar hill foundation Disclosure of Interests: Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Orit Schieir: None declared, Marie-France Valois: None declared, Glen Hazlewood : None declared, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, CArol Hitchon Grant/research support from: Pfizer, UCB (unrelated studies), Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Carter Thorne Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Diane Tin: None declared, Caroline Benson: None declared, Janet Pope Consultant for: Eli Lilly and Company, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie

Background Mechanistic differences between biologics are poorly understood. HLA-DRB1 alleles containing the shared epitope (SE), which are strongly associated with RA, are present in 85% of anti-cyclic citrullinated protein 2 (anti-CCP2) + patients (pts) with RA (Jiang et al. Arthritis Rheumatol 2015). In a prior retrospective exploratory analysis, abatacept (ABA) was more effective in SE+ vs SE- pts (Oryoji et al. Ann Rheum Dis 2017). Head-to-head (H2H) comparisons with other agents are lacking. Objectives This H2H, single-blinded trial (NCT02557100) in biologic-naive pts with early, active RA prospectively explored the relationship between HLA-DRB1 SE and the clinical efficacy of ABA or adalimumab (ADA). Methods Adults with early (=12 mths from symptom onset), moderate-to-severe RA (ACR/EULAR 2010 criteria) seropositive for anti-CCP2 (>3x ULN) and RF, were randomised 1:1 to SC ABA 125mg wkly or SC ADA 40mg every 2 wks (both with stable, oral MTX wkly) for 24 wks. Pts were grouped by SE status (+/-) based on HLA-DRB1 genotype (-: no SE allele; +: =1 SE allele). Safety was analysed throughout the trial and up to 8 wks post last study drug dose. Clinical efficacy was assessed at Wk24 to determine the proportion of ACR20/50/70 responders in ABA vs ADA arms, and the adjusted mean changes from baseline in DAS28 (CRP), SDAI and CDAI. Treatment (tmt) differences between ABA and ADA in SE+ and SE– pts were assessed for ACR20/50/70 responders and DAS28 (CRP) remission at Wk24. Results 80 pts were treated: 40 ABA (9 SE-, 30 SE+, 1 SE unknown) and 40 ADA (9 SE-, 31 SE+). Baseline characteristics were balanced. Mean (SD) age, disease duration and DAS28 (CRP) were 46.0 (14.4) years, 5.5 (2.6) mths and 5.2 (1.1), respectively; 75% were female. No new safety signals were identified. In each arm, related AEs (ABA: 12 [30%]; ADA: 11 [27.5%]) and related serious AEs (ABA: 0; ADA: 1 [2.5%]) were similar. Numerically higher efficacy responses were seen with ABA vs ADA at Wk24 (Table 1). Similar results were observed for DAS28 (CRP), SDAI and CDAI. In SE+ pts, numerically higher efficacy responses were seen with ABA vs ADA at Wk24; 95% CI for estimated tmt differences for ACR20/50/70 responses and DAS28 (CRP) remission did not cross 0 (Figure 1). Conclusion In this seropositive early RA population, numerically higher efficacy responses were seen with abatacept vs adalimumab after 24wks of tmt, with more pronounced tmt differences in SE+ pts. Results are consistent with a previous study in which greater efficacy was seen with abatacept, but not TNF inhibitors, in anti-CCP2+ vs anti-CCP2- pts with RA (Harrold et al. J Rheumatol 2018). Acknowledgement Marianne Peluso (protocol manager); medical writing: Lola Parfitt (Caudex; funding: BMS) Disclosure of Interests William Rigby Consultant for: AbbVie, BMS, Genentech and Pfizer, Jane Buckner Grant/research support from: Janssen, Bristol-Myers Squibb (current); Novo Nordisk, Pfizer, Eli Lilly (past), Consultant for: Bristol-Myers Squibb, Eli Lilly, Lou Bridges: None declared, Marleen Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sheng Gao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Martin Polinsky Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Alyssa Johnsen Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Neelanjana Ray Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron

Background: While treat-to-target strategies can dramatically reduce RA inflammation, persistent fatigue is present in up to half of RA patients, and is an important unmet need. Proposed underlying causes include RA disease, cognitive/emotional/behavioral (CEB), and personal (health) factors. Objectives: To identify risk factors for persistent fatigue at 12-months in men and women with ERA on immunomodulatory therapies. Methods: Data were from patients enrolled in the Canadian Early Arthritis Cohort (CATCH) between 01-2007 and 03-2017 who met 1987 or 2010 ACR/EULAR RA criteria, had active disease treated with DMARDS, and had complete data on DAS28, BMI, and fatigue severity (0-10) over 12-months. Persistent fatigue, was defined as fatigue >4 at baseline with Results: Patients were mostly white (81%), female (71%), with a mean (SD) age of 54 (15), symptom duration of 6 (3) months, and BMI of 28.0 (6.1); 32% were obese (BMI≥30). Women were generally younger, better educated, seropositive, and had greater disability, fatigue, depressive symptoms, and major stress in the past year (p In multivariable regression that included all Table 1 variables, predictors of persistent fatigue in women were obesity (OR 1.7; 95% CI 1.1, 2.6), initial steroid use (OR 1.7; 95% CI 1.1, 2.7), seronegativity (OR 0.6; 95% CI 0.4, 1.0) and poor sleep (OR 1.1; 95% CI 1.0, 1.2). Obesity was the only significant predictor in men and was assoicated with a 2.4 times higher odds (95% CI 1.1, 5.1) of persistent fatigue at 1 yr. Other sociodemographic, RA characteristic, CEB and personal/health factors were not associated with persistent fatigue in either sex in multivariable models. Conclusion: Obesity is common in ERA and a major determinant of persistent fatigue in women and men. In obese RA patients on guideline-based treatment, lifestyle interventions targeting weight loss may play an important role in reducing persistent fatigue that does not improve with RA treatment. Disclosure of Interests: Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie, Orit Schieir: None declared, Marie-France Valois: None declared, Janet Pope Consultant for: Eli Lilly and Company, Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, CArol Hitchon Grant/research support from: Pfizer, UCB (unrelated studies), Carter Thorne Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Diane Tin: None declared, Glen Hazlewood: None declared, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron

Background Pegloticase is a recombinant DNA-produced porcine-like uricase enzyme, which metabolizes relatively insoluble urate to highly soluble allantoin. It is used in the treatment of refractory gout which has failed maximal medical management, typically with xanthine oxidase inhibitors (XOI). Studies have shown a complete responder rate of 42% when defined as repeat serum uric acid (sUA) levels 80% of the time during months 3 and 6 of treatment. Patients that do not maintain a low uric acid while on pegloticase therapy are presumed to have developed anti-drug antibodies (ADA) which rapidly clear the pegloticase molecule. As is routinely utilized in the treatment of other rheumatologic diseases, coadministration of immunomodulatory medications, such as methotrexate, could potentially temper the development of these ADAs (as defined by maintenance of sUA response) in patients treated with pegloticase for refractory gouty arthropathy. Objectives The aim of the current case series was to identify and clinically evaluate patients in a real-world practice setting in order to investigate the utility of adding methotrexate to a pegloticase regimen to increase the durability of response. Methods In this prospective, proof-of-concept, observational case series, 10 sequential patients with refractory tophaceous gouty arthropathy being started on treatment with pegloticase 8 mg every two weeks (as per the label) were identified from 3 separate infusion centers. No inclusion/exclusion criteria were implemented or prescreening performed. Methotrexate (MTX) 15 mg orally once weekly and folic acid 1 mg orally once daily was started one month prior to the initial administration of pegloticase and continued throughout pegloticase treatment. Any infusion pre-medications, which were consistent with standard practices, were administered per the individual physician’s discretion as well as management of any gout flares which occurred during the treatment course. As per standard of care, sUA was measured every two weeks, prior to each subsequent infusion. At the completion of pegloticase treatment for all patients, the number and percentage of patients able to maintain an sUA at goal Results Ten patients ranging in age from 35-80 were identified, from 3 separate infusion centers. There were 143 total pegloticase infusions performed within the observation period. All 10 patients received at least 10 infusions (5 months), 9 patients at least 12 infusions (6 months), 5 patients at least 16 infusions (8 months), 2 patients at least 18 infusions (9 months), and 1 patient received 19 infusions. All 10 patients completed a full course of pegloticase treatment. All patients stayed on MTX 15 mg/week. There were no dose adjustments. 100% of patients were responders as defined by >80% of sUA levels being maintained at goal Conclusion In this proof-of-concept case series of 10 sequential patients, pretreatment and co-administration of methotrexate 15 mg orally once weekly and folic acid 1 mg orally once daily with pegloticase resulted in a 100% maintenance of pegloticase sUA response with no infusion reactions. Although additional studies would be needed to corroborate these results, these data support a potential paradigm shift in treatment of refractory gout with pegloticase. Reference [1] Sundy JS, et al. JAMA. 2011;306:711 Acknowledgement Research sponsored by the Alaska Rheumatology Alliance. Disclosure of Interests John Botson Shareholder of: Publicly traded stock: Horizon, Johnson and Johnson, Pfizer, Rigel, Consultant for: Celgene, Eli Lilly, Genentech, Horizon, Mallinckrodt, Novartis, Pfizer, Speakers bureau: Celgene, Eli Lilly, Horizon, Mallinckrodt, Novartis, Pfizer, Jeff Peterson Consultant for: Celgene, Genentech, Horizon, Lilly, Novartis, Regeneron (2017-2018), Speakers bureau: Abbvie, Horizon, Lilly, Novartis (2017-2018)

Background Secukinumab (SEC) provided sustained clinical efficacy, and inhibition of radiographic progression over 52 Weeks (Wks) in patients (pts) with psoriatic arthritis (PsA) in the FUTURE 5 study1. Objectives To report the effect of SEC on radiographic progression at Wk 104 (2 years) in PsA pts in the FUTURE 5 study. Methods Adults (N=996) with active PsA, stratified by prior anti-TNF therapy (naive and inadequate response/intolerance [IR]) were randomised 2:2:2:3 to subcutaneous SEC 300mg with loading dose (LD; 300mg), 150mg LD (150mg), 150mg no LD, or placebo at baseline (BL), Wks 1, 2, 3, 4, and every 4 wks thereafter. Pts could have SEC dose escalated from 150 to 300 mg starting from Wk 52, based on physicians9 judgement. Data are shown for pts originally randomised to SEC; 150mg groups include pts who had dose escalated to 300mg. Concomitant MTX (≤25 mg/week) was allowed. Radiographic progression (mean change in van der Heijde-modified total Sharp score [vdH-mTSS] and its components: erosion and joint space narrowing [JSN] scores, was based on hand/wrist/foot X-rays obtained at BL and Wk 104, and assessed by two blinded readers (plus an adjudicator if required). Other efficacy endpoints included ACR20/50, PASI90 and resolution of dactylitis and enthesitis. Results Overall, 84.7% (300mg), 82.3% (150mg) and 75.2% (150mg no LD) pts completed 2 years of treatment. A total of 86 (39%) and 92 (41%) pts had their dose escalated to 300mg in the 150mg and 150mg no LD groups, respectively. Inhibition of radiographic progression was sustained with SEC through 2 years (Table 1). Proportions of pts with no radiographic progression (change from BL in mTSS ≤0.5) with SEC were 89.5% (300 mg), 82.3% (150 mg), and 81.1% (150 mg no LD) at 2 years; corresponding proportion of pts for change from BL in mTSS ≤0.0 were: 81.2%, 69.1% and 73.4%, respectively. Clinical responses were also sustained through 2 years (Table 1). Conclusion Subcutaneous secukinumab provided sustained inhibition of radiographic progression and sustained clinical responses through 2 years of treatment in pts with active PsA. Reference [1] Mease PJ et al. Arthritis Rheumatol 2018;70(suppl 10). Disclosure of Interests Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., and UCB., Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., and UCB., Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Leo, Merck, Novartis, Pfizer and UCB.., Robert B.M. Landewe: None declared, Proton Rahman Grant/research support from: Investigator for Janssen Research & Development, LLC and Novartis, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly,Novartis, and UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, and Novartis, Hasan Tahir Grant/research support from: Novartis, Eli-Lilly, Speakers bureau: AbbVie, Janssen, Eli Lilly, and Novartis, Atul Singhal Grant/research support from: AAbbVie, Gilead, Sanofi, Regeneron, Amgen, Roche, BMS, Janssen, Lilly, Novartis, Pfizer, UCB, Astra Zeneca, MedImmune, FujiFilm, Nichi-Iko, Mallinckrodt, Speakers bureau: AbbVie, Elke Boettcher Consultant for: Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis, Speakers bureau: Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis, Sandra Navarra Speakers bureau: Astellas, Johnson & Johnson, Novartis, Pfizer, Aimee Readie Shareholder of: Novartis, Employee of: Novartis, Shephard Mpofu Shareholder of: Novartis, Employee of: Novartis, Eumorphia Maria Delicha Consultant for: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Desiree van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge

Background The sense of smell is sensitive to hundreds of thousands of odorants. Smell disorders significantly compromise the quality of life. A National Health and Nutrition Examination Survey (NHANES) 2013-2014 survey among US population aged 40 years of age and older years found smell dysfunction in ∼ 20.5 million (13.5%) of Americans (1). Prevalence increased with age. Other factors influencing the sense of smell include ethnicity, smoking, medications, head trauma, chronic sinusitis, upper respiratory tract infections, alcoholism and neurological disorders. The University of Pennsylvania Smell Identification Test (UPSIT) (2) is a well-validated test of olfactory function that correlates with odor detection and other quantitative measures of olfaction. This test has become the ‘gold standard’ for olfactory testing and is comprised of four test booklets, each containing 10 microencapsulated (scratch & sniff) odors. Patients with gout, the most common inflammatory arthritis, frequently have multiple associated comorbidities, affecting many organs and aspects of one’s health. Objectives To determine whether gout patients have an impaired sense of smell. Methods This was a cross-sectional prospective study of gout patients seen in our rheumatology clinic. The first 30 clinic patients were recruited during the period 7/15/17-5/25/18. Each patient was administered the 40-item UPSIT. UPSIT scores were compared to age- and sex-matched controls from a normative database maintained at the University of Pennsylvania Smell and Taste Center using a paired t-test. Results Gout patients ranged in age from 31 - 86 years (mean: 59 years); 26 (87%) of patients were ≥ 40 years old and included 26 men and 4 women. The duration of gout ranged from 1- 43 years (mean: 9 years), with 19 having gout for >5 years. Visible tophi were observed in 6 patients (33%). C-reactive protein was within normal range except in one gout patient. Serum urate levels ranged from 5.1-12 mg/dL (mean: 6.29 mg/dL). Two patients were current smokers; both have microsomia. No patients had head trauma, chronic sinusitis, upper respiratory tract infections, alcoholism or neurological disorders. The mean UPSIT scores of the two groups did not differ significantly [respective patient and control means (SDs) = 31.40 (5.79) and 31.80 (4.37); t29 = -0.342, p = 0.74]. Conclusion This is the first study to quantitatively assess smell function in patients with gout. Despite being a systemic inflammatory disease, with multiple assocaited comorbidities, we did not find a statistically significant effect of gout on smell function using a well validated olfactory test. References [1] Liu G, Zong G, Doty RL, Sun Q. Prevalence and risk factors of taste and smell impairment in a nationwide representative sample of the US population: a cross-sectional study. BMJ Open2016;6:e013246. [2] Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav1984;32:489-502. Disclosure of Interests Naomi Schlesinger Grant/research support from: Pfizer, Consultant for: YesNovartis, Horizon Pharma, Proteo Thera, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Mohamed Elsaid: None declared, Vinod Rustgi Grant/research support from: Genfit, Consultant for: yes Allergan, Zydus, Abbvie

Background Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease that can involve peripheral and axial joints, skin, and entheses. A number of validated composite indices have been developed, not only to measure overall disease activity for PsA, but also to provide thresholds for treat-to-target goals. These include MDA (Minimal Disease Activity), DAPSA (Disease Activity in PsA), and PASDAS (PsA Disease Activity Score). We have previously demonstrated that higher proportions of PsA patients treated with ixekizumab (IXE), a monoclonal antibody that selectivity targets interleukin-17A, achieved therapeutic thresholds defined by MDA, DAPSA, and PASDAS versus placebo (PBO) up to Week 24.1 Objectives To explore the extent to which IXE can help biologic-naive and tumor necrosis factor inhibitor (TNFi) inadequate responder patients achieve treat-to-target goals, as defined by composite indices incorporating multiple disease domains, through 108 weeks of treatment. Methods Data were analyzed from all patients initially randomized to 80 mg IXE every 4 weeks after a 160-mg starting dose in 2 double-blind, PBO-controlled phase III trials investigating the efficacy and safety of IXE. For SPIRIT-P1 (NCT01695239), patients (N=107) were bDMARD naive. For SPIRIT-P2 (NCT02349295), patients (N=122) had an inadequate response or were intolerant to TNFis. The following composite measures and definitions were used: MDA and Very Low Disease Activity (VLDA) (see Figure); DAPSA Low Disease Activity (LDA) (≤14 and >4) and remission (≤4); PASDAS LDA/VLDA (≤3.2/≤1.9); and GRACE (GRAppa Composite score) LDA (≤2.3). Modified nonresponder imputation (mNRI; missing data treated as nonresponse for patients discontinued due to lack of efficacy or adverse events; multiple imputation for all other missing data) was used for all analyses. Results Therapeutic threshold results at Week 108 are summarized in the Figure. Whether measured using MDA, DAPSA, PASDAS, or GRACE, the proportions of IXE-treated patients achieving designated therapeutic thresholds were sustained through 2 years of treatment. Efficacy was similar between SPIRIT-P1 and SPIRIT-P2. Conclusion High proportions of IXE-treated patients, whether biologic naive or TNFi inadequate responders, achieved treat-to-target goals, as defined by composite indices incorporating multiple disease domains, through 2 years of treatment. References [1] Coates L, et al. Ann Rheum Dis. 2018;77(Suppl):A375. Disclosure of Interests Laura C Coates Grant/research support from: AbbVie, Celgene, Lilly, Novartis and Pfizer, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead Sciences Inc., Janssen, Lilly, Novartis, Pfizer, Prothena Corp and UCB, Alexis Ogdie Grant/research support from: (To my university) Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly and Company, Novartis, Pfizer, and Takeda, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer Inc, Takeda, Consultant for: Abbvie, Amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Consultant for: Abbvie, Amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Prashanth Sunkureddi Shareholder of: Pfizer, Johnson and Johnson, Mallinckrodt, Regeneron, Grant/research support from: Clinical research trials for Eli Lilly, Novartis, Amgen, Pfizer, Consultant for: Eli Lilly, Novartis, AbbVie, Pfizer, Speakers bureau: Eli Lilly, Novartis, AbbVie, Sanofi Genzyme, Regeneron, Pfizer, Lisa Kerr Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Matthew Hufford Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Philip Helliwell Grant/research support from: Paid to charity: from AbbVie, Janssen and Novartis, Consultant for: Paid to charity: from AbbVie, Amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos

Background Up to 80% of rheumatoid arthritis patients report clinically relevant fatigue.1 Fatigue is complex multi-factorial process that can result in adverse affects on patients’ physical and emotional well-being.2 Objectives To examine the relationship between disease activity and fatigue over time in early rheumatoid arthritis (ERA). Methods Data were from patients with ERA (symptoms ≤ 12 months) enrolled in the Canadian Early Arthritis Cohort (CATCH). CATCH participants completed repeat clinical assessments, laboratory investigations and self-reported questionnaires including rating their fatigue over the past week using a 10 point numerical rating scale (NRS). Fatigue severity was classified as low (≤2); moderate (>2 but Results Of the 1864 patients included, 1640 (88%) met criteria for RA, 1342 (72%) were women and most had moderate-high baseline disease with a mean (SD) DAS28 of 4.9 (1.5). Fatigue was common with 19% reporting moderate and 59% severe fatigue at baseline. Fatigue was positively and strongly correlated with pain and patient global ratings (r 0.56-0.67, p DAS28: disease activity score in 28 joints; REM: remission; LDA: low disease activity; MDA: moderate disease activity; HDA: high disease activity. Conclusion Fatigue is common in ERA and is most strongly correlated with pain and disease activity. Early treatment response within 3-months was associated with short and long-term improvements in fatigue over time. Further longitudinal research examining the time-varing effects of both clinical and psychosocial factors on fatigue is needed. References [1] Pollard, LC., Choy, HE., Gonzalez, J., Khoshaba, B., and Scott, DL. Fatigue in rheumatoid arthritis reflects pain, not disease activity. Rheumatology. 2006;45:885-889. [2] Nikolaus, S., Bode, C., Taal, E., and Van De Laar, MA. Fatigue and Factors Relating to Fatigue in Rheumatoid Arthritis: A systematic Review. American College of Rheumatology. 2013;65:1128-1146. Acknowledgement On behalf of Canadian Early Arthritis Cohort (CATCH) Investigators Disclosure of Interests Melissa Holdren: None declared, Orit Schieir: None declared, Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie, Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Glen Hazlewood : None declared, CArol Hitchon Grant/research support from: Pfizer, UCB (unrelated studies), Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Diane Tin: None declared, Carter Thorne Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Janet Pope Consultant for: Eli Lilly and Company

Background: Repository corticotropin injection (RCI) is a complex mixture containing purified porcine pituitary adrenocorticotropic hormone (ACTH)-analogue with potential anti–inflammatory and immunomodulatory effects through the melanocortin receptors (MC1R, MC3R-MC5R) and endogenous steroid production. RCI is approved by the US FDA for the treatment of acute exacerbations (ie, disease flares) or as maintenance therapy in patients with systemic lupus erythematosus (SLE). In a pilot study, RCI was well tolerated with improvements in disease activity for lupus patients treated with RCI compared to those who received placebo (Furie et al, 2016). Objectives: To discuss the design, demographics, and baseline characteristics of a clinical trial evaluating the role of RCI in the treatment of patients with inadequately controlled SLE disease activity. Methods: This is a multicenter, double-blind, randomized, placebo-controlled, 24-week clinical trial aiming to determine the effect of RCI in reducing disease activity for patients with persistently active SLE despite moderate-dose corticosteroids (CSs). Patients are required to have SLE (≥4 of 11 ACR criteria from 1997) and active disease (moderate to severe rash and/or arthritis) despite stable dose CSs ≥ 4 weeks prior to screening (7.5 - 30 mg/day of prednisone or equivalent). Patients are treated with RCI 1 mL (80 U) subcutaneously (SC) or placebo 1 mL, every other day for 4 weeks followed by twice per week for 20 weeks. Randomization is stratified by study site location and prednisone or equivalent dose (≤ 20 and > 20 mg/day). Patients remain on stable doses of CSs through Week 16, with tapering encouraged between Weeks 16 and 24. Efficacy is evaluated using the SLE Responder Index-4 (SRI-4) and changes from baseline in SLE Disease Activity Index-2000 (SLEDAI-2K), British Isles Lupus Assessment Group-2004 (BILAG-2004) scores, and Physician’s Global Assessment (PGA). The primary efficacy endpoint is the proportion of SRI-4 responders at Week 16. Secondary and exploratory endpoints include changes in disease activity scores over time, prednisone dose, and biomarkers (ie, complements, autoantibodies, inflammatory, bone turnover). Results: As of 14 December 2018, 124 patients comprised the intent–to–treat (ITT) population. Target enrollment is 270 patients, of which 162 patients are expected to be randomized at approximately 60 sites globally. Demographic and baseline characteristics (Table) were collected, including circulating lymphocyte profiles (CD19+ B Cells, CD3+ total T cells, and CD4 Treg cells), which are consistent with the pilot study of RCI (Furie et al, 2016). Conclusion: This on-going study assesses the efficacy and safety of RCI for the treatment of refractory SLE in a racially and ethnically diverse population. The rapid onset of action of RCI allows for a 16–week primary endpoint. Patients enrolled in this trial have moderate or high disease activity (as shown by the mean SLEDAI-2K, BILAG, and PGA) and are likely to provide valuable data on the role of RCI in refractory lupus. Bone turnover markers will further define the safety profile of RCI in lupus. Reference: [1] Furie, et al. Lupus Sci Med. 2016 Oct 21;3:e000180. Acknowledgement: Editorial support provided by MedLogix Communications, LLC and funded by Mallinckrodt, ARD LLC. Disclosure of Interests: Anca Askanase: None declared, Enxu Zhao Shareholder of: Mallinckrodt ARD LLC, Employee of: Mallinckrodt ARD LLC, Julie Zhu Shareholder of: Mallinckrodt ARC, LLC, Employee of: Mallinckrodt ARC, LLC, Erin Connolly-Strong Shareholder of: Mallinckrodt ARC, LLC, Employee of: Mallinckrodt ARC, LLC, Richard Furie Grant/research support from: Biogen, UCB Pharma, but not in the last 12 months, Consultant for: Biogen, UCB Pharma, but not in the last 12 months

Background Prevalence studies of metabolic syndrome (MetS) in early rheumatoid arthritis (ERA) are sparse and estimates are variable. Differences by sex and menopausal status have not been formally assessed. Objectives We estimated prevalence and factors associated with MetS in ERA patients treated in routine practice settings. Variations by sex, and by menopausal status were also examined. Methods Cross-sectional data were analyzed from patients meeting 1987 or 2010 ACR/EULAR RA criteria enrolled in the Canadian Early Arthritis Cohort (CATCH) from January 2007-March 2017. CATCH is a prospective multicenter observational study of patients diagnosed and treated for early inflammatory arthritis (symptoms Results The sample included 1543 participants; 71% were female and mean(SD) age was 54 (15) years. 476 (31%) of the total sample met criteria for MetS. Participants with MetS were older, more frequently past smokers and reported more comorbid conditions, including cardiovascular disease (CVD) (p Conclusion Approximately 1 in 3 ERA patients met crietria for MetS. Though men had a higher prevalence of MetS and individual MetS components, post-menopausal women had a similar MetS profile as men, and should equally be considered high risk for CVD development. Characteristics and associations with MetS differed in men and women suggesting sex-specific variations are important considerations for comorbidity screening and surveillance of CVD outcomes in ERA. Reference [1] Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15(7):539-53. Acknowledgement Sponsors: Amgen & Pfizer-Founding sponsors 2007+; AbbVie 2011+; Medexus 2013+;EliLilly2016+, Merck Canada 2017+, Hoffmann-LaRoche & Janssen Biotect 2011-2016, UCB & BMS 2011-2018, Sanofi-Genzyme 2016-2017. Disclosure of Interests Bindee Kuriya Consultant for: Advisory Board Member: Abbvie, Sanofi Genzyme, Eli Lilly, Pfizer Canada, Roche, Orit Schieir: None declared, Marie-France Valois: None declared, Janet Pope Consultant for: Eli Lilly and Company, Gilles Boire Grant/research support from: Investigator-initiated studies: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Consultant for: Advisory boards: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Glen Hazlewood : None declared, Carter Thorne Grant/research support from: Investigator-initiated studies: Amgen, Pfizer. RCTs: Abbvie, Celgene, CaREBiodam, Novartis, Pfizer, Consultant for: Advisory board: Abbvie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi. Consultant: Abbvie, Centocor, Janssen, Lilly, Medexus/Medac, Pfizer, Speakers bureau: Medexus/Medac, Diane Tin: None declared, CArol Hitchon Grant/research support from: Pfizer, UCB (unrelated studies), Susan J. Bartlett Consultant for: Pfizer, UCB, Lilly, Novartis, Merck, Jansen, Abbvie, Edward Keystone Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, Consultant for: AbbVie, Amgen, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, UCB., Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Lillian Barra: None declared

Background Nail psoriasis (PsO) is present in up to 80% in psoriatic arthritis (PsA) patients (pts) and associated with significant pain, psychosocial disability, decreased physical function and quality of life (QoL).1 Nail PsO is considered as one of the six core PsA domains by GRAPPA2 and is a predictor of severe disease with joint involvement and structural damage. Secukinumab (SEC) has demonstrated efficacy for pts with nail PsO in the TRANSFIGURE study3 and significant improvement in signs and symptoms of PsA in the FUTURE 5 study4 Objectives To evaluate the efficacy of SEC on nail PsO and other facets of disease in the nail subset from the FUTURE 5 study through 52 weeks (wks). Methods Pts (N=996) with active PsA, were randomised to subcutaneous SEC 300 mg loading dosage (LD; 300 mg), 150 mg LD (150 mg), 150 mg no LD or placebo (PBO). All groups received SEC or PBO at baseline (BL), Wks 1, 2, 3, and 4, and then every 4 wks. Efficacy assessments through Wk 52 included mNAPSI, ACR, PASI, HAQ-DI, SF-36 PCS, PsAQoL and resolution of dactylitis and enthesitis. Analyses through Wk 16 used non-responder imputation (NRI) for binary and mixed-effect model repeated measure (MMRM) for continuous variables. Observed data are presented from Wk 20-52. Results A total of 663/996 (66.6%) PsA pts had concomitant nail PsO at BL. Demographics and BL disease characteristics were balanced between treatment groups in the nail subset, which were comparable with overall population. The total mean mNAPSI score at BL was 16.4. SEC 300 and 150 mg doses improved nail PsO vs. placebo (PBO) at Wk 8, 12 and 16 (P Conclusion Secukinumab provided sustained improvements in nail disease, signs and symptoms of PsA, physical function and QoL through 52 wks in pts with PsA and moderate to severe nail PsO. References [1] Baran R. Dermatology2010;221(Suppl1):1-5. [2] Coates LC, et al. Arthritis Rheumatol. 2016;68:1060-71. [3] Reich K, et al. Br J Dermatol. 2018. Doi: 10.1111/bjd.17351. [4] Mease PJ, et al. Ann Rheum Dis. 2018;77:890-7. Disclosure of Interests Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: AbbVie, Amgen, BMS, Galapagos, Gilead Sciences, Inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Bruce Kirkham Grant/research support from: Abbvie, Janssen, Lilly, Novartis, Roche, UCB, Consultant for: Abbvie, Janssen, Lilly, Novartis, Roche, UCB, Speakers bureau: Abbvie, Janssen, Lilly, Novartis, Roche, UCB, Alejandro Balsa Grant/research support from: Abbvie, Pfizer, Novartis, BMS, Nordic, Sanofi, Consultant for: Abbvie, Pfizer, Novartis, BMS, Nordic, Sanofi, Sandoz, Lilly, Paid instructor for: Pfizer, Speakers bureau: Pfizer, Novartis, UCB, Nordic, Sanofi, Sandoz, Lilly, Atul Singhal Grant/research support from: AbbVie, Gilead, Sanofi, Regeneron, Amgen, Roche, BMS, Janssen, Lilly, Novartis, Pfizer, UCB, Astra Zeneca, MedImmune, FujiFilm, Nichi-Iko, Mallinckrodt, Speakers bureau: AbbVie, Erhard Quebe-Fehling Shareholder of: Novartis, Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Corine Gaillez Shareholder of: Novartis, BMS, Employee of: Novartis

Background Despite its modest efficacy, guidelines consistently recommend paracetamol as a first-line analgesic for osteoarthritis (OA) based on its perceived safety. However, there is growing controversy, highlighted in the National Institute for Health and Care Excellence OA (NICE) 2014 guidance on OA, that paracetamol is not as safe as previously thought, especially at the highest therapeutic dose of 4gm/day. Objectives To investigate the association between paracetamol and gastrointestinal, liver, renal and cardiovascular adverse events both in randomised controlled trials (RCTs) and observational studies. Methods We systematically searched MEDLINE, EMBASE, PUBMED, AHMED, CINAHL, Web of Science, and Google Scholar for published literature in any language to the end of November 2018 for (1) RCTs of paracetamol in symptomatic OA, and (2) observational studies irrespective of any underlying condition, to determine the risk of gastrointestinal, liver, renal and cardiovascular adverse events. We included studies assessing oral paracetamol in people aged ≥18 years and reporting on clinically relevant adverse effects. Risk ratio (RR) and 95% confidence interval (CI) were estimated for RCT and cohort studies, whereas odds ratio (OR) and 95% CI were used for case-control studies. Results were pooled as appropriate using random effects model. The risk of bias was assessed using modified Cochrane tool for RCTS and Newcastle Ottawa scale for observational studies. Results We reviewed titles and abstracts of 3,622 records in the systematic search (1,997 RCTs and 1,635 observational studies). After examining full papers 23 RCTs (7,863 participants), 15 cohort studies (2,262,517 participants) and 34 case-control studies (441,638 participants) met inclusion criteria. Compared to placebo, paracetamol was associated with increased incidence of treatment-related adverse events (RR 1.35, 95% CI 1.04 to 1.75), especially diarrhoea (RR 2.14, 95% CI 1.35 to 3.37) and abnormal liver function (RR 3.99, 95% CI 2.05 to 7.77). The pooled OR from twelve age and gender matched case-control studies (7894 participants) was 1.36 (95% CI 1.13 to 1.64) for upper gastrointestinal bleeding. In addition, a dose response relationship was observed in a cohort study (382,404 participants) for this outcome. The RR was 1.11 (95% CI 1.04 to 1.21) with low dose paracetamol (measured as medication possession rate) and 1.49 (95% CI 1.29 to 1.71) with high dose paracetamol. Paracetamol was not associated with cardiovascular events in two RCTs (775 participants) (RR 1.27, 95% CI 0.06 to 27.77) and three case-control studies (42,180 participants) (OR 0.97, 95% CI 0.77 to 1.21), but in three cohort studies (208,926 participants) (RR 1.35, 95% CI 1.14 to 1.59). There were insufficient data in RCTs and case-control studies for renal adverse events. However, three cohort studies (7,360 participants) demonstrated a dose response relationship between paracetamol and renal function impairment (defined as ≥30 percentage decrease in estimated glomerular filtration rate). The data of these three cohort studies could not be pooled due to different doses of paracetamol. One cohort study (1697 participants) reported RR of 1.40 (95% CI 0.79 to 2.48) for renal impairment for paracetamol 100-499g, and 2.19 (95% CI 1.4 to 3.43) for paracetamol >3000g. Conclusion Paracetamol is associated with diarrhoea and abnormal liver function in short-term trial data, and with upper GI bleeding and renal impairment in long-term observational data. Methodological limitations of observational data, such as channelling bias, may confound the results. Large-scale well-designed prospective studies are needed to ascertain the long-term safety of paracetamol. Disclosure of Interests Jaspreet Kaur: None declared, Burak Kundaki: None declared, Georgina Nakafero: None declared, Abhishek Abhishek Grant/research support from: AstraZeneca and OxfordImmunotech, Grant/research support from: AstraZeneca and Oxford Immunotech, Speakers bureau: Menarini pharmaceuticals, Speakers bureau: Menarini pharmaceuticals, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant for: Advisory Boards on Grunenthal and Mallinckrodt, Weiya Zhang Consultant for: Grunenthal for advice on gout management, Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium

Background: Certolizumab pegol (CZP) is an anti-TNF drug approved for rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn’s disease (CD). Older age, comorbidity burden and corticosteroid (CS) use have been linked to increased risk of serious infectious events (SIEs) in CZP-treated patients (pts) with RA.1 However, the impact of overall disease burden on the risk of serious adverse events (SAEs) has not been fully examined for other CZP indications. High body mass index (BMI) has been associated with systemic inflammation and greater comorbidity risk.2,3 Greater disease burden in these pts may lead to increased CS use – a known risk factor for SAEs.1 Objectives: To examine the contribution of BMI and CS use to the risk of SIEs, malignancies and major adverse cardiovascular events (MACE) in CZP-treated pts across indications. Methods: Safety data were pooled across 49 CZP clinical trials (27 RA, 1 axSpA, 1 PsA, 5 PSO, 15 CD). SAEs of potential concern were medically reviewed by an external expert committee using predefined case rules. Incidence rates (IR) were calculated per 100 pt–years (PY). Multivariate Cox modeling was used to estimate relative risk (hazard ratio [HR]) of time to first SIE, malignancy or MACE by baseline BMI ( Results: Across indications, 11,317 pts received CZP (21,695 PY total exposure; max: 7.8 years [yrs]; exposure for RA: 13,542 PY; axSpA: 978 PY; PsA: 1,316 PY; PSO: 1,481 PY; CD: 4,378 PY). Mean BMI was 27.8 kg/m2 in RA, 27.6 kg/m2 in axSpA, 29.8 kg/m2 in PsA, 30.1 kg/m2 in PSO, and 24.0 kg/m2 in CD. Overall, 4,132 pts (37%) took CS at baseline, more so in RA (46%) and axSpA (51%). Across indications, IRs were 0.82/100 PY for all malignancies (IR for malignancies excluding non-melanoma skin cancer [NMSC] was 0.66/100 PY), 0.47/100 PY for MACE, and 3.62/100 PY for SIEs. According to the Cox model, age ≥45 yrs, disease duration Conclusion: In CZP-treated pts across indications, malignancy risk was not influenced by BMI or CS use. As expected, obesity and CS use increased the risk of MACE. The SIE risk associated with CS use was compounded in obese pts, which may reflect the contribution of comorbidities, disease activity or other factors not examined here. References [1] Curtis J. Arthritis Res Ther 2017;19:276; 2. Perez de Heredia F. Proc Nutr Soc 2012;71:332–8; 3. Harpsoe M. Int J Epidemiol 2014;43:843–55. Acknowledgement: We thank the patients who participated. This study was funded by UCB Pharma, medical writing by Emma Phillips, Costello Medical, UK. Disclosure of Interests: Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Andrew Blauvelt Grant/research support from: AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira Inc, Eli Lilly and Company, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, LEO, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharmaceuticals, UCB Pharma, Valeant, Vidac, Consultant for: AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira Inc., Eli Lilly and Company, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, LEO, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharmaceuticals, UCB Pharma, Valeant, Vidac., Speakers bureau: Janssen, Regeneron, Sanofi Genzyme, Jeffrey Curtis: None declared, Cecile Gaujoux-Viala Consultant for: Speaking and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Merck-Serono, Medac, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma., Speakers bureau: Speaking and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Merck-Serono, Medac, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma., Tore K. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB., Consultant for: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Pfizer, Roche, Sandoz, Sanofi, Mylan and UCB, Speakers bureau: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Oktal, Orion Pharma, Pfizer, Roche, Sandoz, Sanofi and UCB, William Sandborn Shareholder of: Stock options from Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Precision IBD, Progenity and Ritter Pharmaceuticals, Grant/research support from: Research grants from Atlantic Healthcare Limited, AbbVie, Amgen, Celgene/Receptos, Genentech, Gilead Sciences, Janssen, Lilly and Takeda, Consultant for: Consulting fees from AbbVie, Allergan, Amgen, Boehringer Ingelheim, Celgene, Conatus, Cosmo, Escalier Biosciences, Ferring, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Miraca Life Sciences, Nivalis Therapeutics, Novartis Nutrition Science Partners, Oppilan Pharma, Otsuka, Paul Hastings, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust or HART), Salix, Shire, Seres Therapeutics, Sigmoid Biotechnologies, Takeda, Tigenix, Tillotts Pharma, UCB Pharma and Vivelix, Kevin Winthrop Consultant for: Gilead, Galapagos, Eli Lilly and Company, Abbvie, Pfizer, GSK, Christina Popova Employee of: Employee of UCB Pharma., Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma

Background: Data-driven principal component (PC) and cluster analysis has the potential to identify previously unknown patient subgroups within a rheumatoid arthritis (RA) registry to establish prognosis, predict disease trajectory, and help inform treatment. Objectives: The Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS), established in 2003, is a single-center, prospective observational registry cohort providing a comprehensive set of clinical disease activity measures in >1400 patients with RA. Our objective was to use PC and cluster analysis of baseline demographic, socio-economic, health and disease characteristics in BRASS to identify and characterize distinct patient clusters in RA. Methods: Patient variables recorded at entry into BRASS were refined and combined using PC analysis to reduce dimensionality and collinearity. The number of PCs was established by eigenvalue >1, cumulative variance, and interpretability. Patients were clustered using a k-means approach with non-hierarchical, exclusive, and complete clustering, with minimum cluster size 5% of population, and maximum 19 clusters. The final number of clusters was determined according to the cubic clustering criterion and pseudo F. Results: Analysis of baseline data from 1443 patients identified 41 PCs that capture the fundamental characteristics involved in RA. Cluster analysis distinguished 5 patient clusters. Each cluster reflected a different profile of PCs, and can be described based on overall health, RA disease activity and duration (Table). Key differentiators between clusters include comorbidity PCs (metabolic comorbidities predominate in cluster 1, neurologic in cluster 4, and orthopedic in cluster 5) and patient characteristics/social PCs (greatest number of doctor visits and family history of MI in cluster 3, greatest BMI in cluster 1, highest income in cluster 2, lowest income in cluster 5, and least emotional support in cluster 1). Conclusion: Data-driven cluster analysis of RA patient characteristics at entry into the BRASS registry identified five distinct patient phenotypes, providing a convenient method to potentially derive novel insights into the multifactorial drivers, commonly co-occurring health conditions, and manifestations of RA. Investigation of longitudinal outcomes in these different clusters in the BRASS registry and validation in an independent dataset is ongoing. Acknowledgement: Study funding and medical writing support (Matt Lewis, Adelphi) provided by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interests: Jeffrey R. Curtis Grant/research support from: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Crescendo Bioscience Inc., Consultant for: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Crescendo Bioscience Inc., Michael E. Weinblatt Shareholder of: Stock option: CanFite, Lycera, Scipher, Inmedix, Grant/research support from: Crescendo Bioscience, Bristol Myers Squibb, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, CanFite, Corrona, Crescendo, GlaxoSmithKline, Gilead, Horizon, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Scipher, Set Point, Kenneth Saag Grant/research support from: Amgen, Ironwood/AstraZeneca, Horizon, SOBI, Takeda, Consultant for: Abbvie, Amgen, Ironwood/AstraZeneca, Bayer, Gilead, Horizon, Kowa, Radius, Roche/Genentech, SOBI, Takeda, Teijin, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Christina Charles-Schoeman Grant/research support from: Bristol-Myers Squibb, AbbVie, and Pfizer, Consultant for: Regeneron-Sanofi, Pfizer, and Gilead, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi, Gregory St. John Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Toshio Kimura Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Shen Zheng Consultant for: Sanofi, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Grace Wright Consultant for: Abbvie, Amgen, BMS, Exagen, LILLY, Myriad Autoimmune, NOVARTIS, Pfizer, Sanofi Genzyme Regeneron, UCB, Speakers bureau: Abbvie, Amgen, BMS, Exagen, LILLY, Myriad Autoimmune, NOVARTIS, Sanofi Genzyme Regeneron, UCB, Martin Bergman Shareholder of: Johnson and Johnson (parent company of Janssen), Consultant for: AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron, Kamala Nola Shareholder of: Gilead, Johnson & Johnson, Proctor & Gamble, Consultant for: Yes – Gilead, Sanofi Genzyme, Regeneron, Speakers bureau: Coherus, Daniel E. Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS Corbus, NIH, Novartis, Pfizer, Roche/Genentech, Consultant for: AbbVie, Actelion, Amgen, BMS, Cytori, Novartis, Pfizer, Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), Nancy Shadick Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron.

Background Since the introduction of anti-TNF biosimilars in routine clinical practice, there has been a drive to implement the switch program for all biosimilars at the point of availability. Etanercept biosimilar (SB4) was granted marketing authorisation by the EMA in January 2016. Our Trust was one of the leading centres to switch all patients within one year of the drug’s availability. The aim of the non-medical switch was to obtain significant savings for the NHS whilst achieving similar clinical outcomes. Objectives We report patient experience after a year of completing the switch program. Methods A list of all patients prescribed etanercept was extracted through our database. The original strategy included a ‘switch’ letter sent to all patients including SB4 information sheet. Patients were given the opportunity to contact nurse helpline for information or if disease control worsened/adverse effects developed. We reviewed all relevant records and collected data on any adverse events and disease outcome on either side of the switch. Results 84 patients were prescribed reference etanercept. 41 (49%) had RA, 17 (20%) had PsA, 18 (21%) had AS and remaining eight had JIA. One person declined the transfer to the biosimilar and one patient with JIA was on 37.5mg weekly dose which was unavailable. 82 agreed to the switch that was completed by March 2017. Median age of switchers was 59.6 (range 14-74 years). 25 (30%) were men and remaining 59 (75%) were women. 76 patients remain on SB4 biosimilar a year after switch. Seven patients described concerns within the first five months of switching. One was found to have concurrent severe Vit D deficiency which upon correcting allowed him to continue with the biosimilar. Six patients had side effects with corresponding worsening of respective disease activity scores. Four returned to the originator with resolution of adverse effects and disease control was regained. Two continued to have uncontrolled disease and were moved to alternative mode of action. Conclusion Overall patient experience following etanercept biosimilar switch has been positive. 90% continue with SB4 originator a year later with no adverse outcomes. All were happy to switch after receiving a letter and having the opportunity to contact if necessary. This made the process quite smooth, easy to administer and avoided costs associated with face-to-face review. Substantial annual cost savings of nearly £100,000 were achieved once the switch process completed. Only six patients (7%) encountered adverse effects, two of whom had uncontrolled diease despite switching back to the originator. We support the routine switching from originator to biosimilar etanercept in view of good patient experience and disease outcomes. This can be achieved with minimal contact in a cost-efficient manner. Disclosure of Interests Muhammad Khurram Nisar Grant/research support from: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Novartis, Celgene, Mallinckrodt, UCB and Lilly, Consultant for: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Novartis, Celgene, Mallinckrodt, UCB and Lilly, Speakers bureau: Muhammad Nisar undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, Abbvie, Pfizer, BMS, Novartis, Celgene, Mallinckrodt, UCB and Lilly

Background Rheumatology Nurse Practice is an accredited educational initiative spearheaded by members of the Rheumatology Nurses Societys Board of Directors and Education Department that has been ongoing for the last 10 years. It involves a combination of print issues and live broadcasts geared toward rheumatology nurses, nurse practitioners, and physician assistants. In 2017, nine evidence-based print issues were published along with nine corresponding case-based live broadcasts using the Google Hangouts On Air platform. To gauge the impact of this education, a special cohort of 100 learners was recruited at the start of 2017 to provide in-depth feedback through the completion of detailed pre- and post- activity surveys. This abstract focuses on feedback from four issues of Rheumatology Nurse Practice that centered on the following topics: New Insights into the Treatment of the Spondyloarthropathies Looking at the Horizon: What Does the Future Hold in the Treatment of Rheumatoid Arthritis? The Pathophysiology of Spondyloarthritis: Connecting and Differentiating Characteristics The Pathophysiology of Systemic Lupus Erythematosus: A Nursing Primer Objectives To gauge improvements in learners knowledge, competence, and performance as a result of this education. Specific learning objectives were tied to each print issue of Rheumatology Nurse Practice and served as the basis for the pre- and post-activity surveys. Methods Each print issue contained a combination of evidence-based content related to the main theme, along with a series of individual essays written by activity faculty members. These essays all also linked to the main theme of the issue. Live broadcasts were intended to bring a real-life, case-based perspective to the education. Results Improvements of >25% in both knowledge and competence were noted between pre- vs. post-activity cohort surveys for all issues in this initiative. Learners also provided extensive feedback regarding specific areas of improvement within their day-to-day practice based on the education. Conclusion Print issues and online broadcasts within the Rheumatology Nurse Practice initiative are valued resources, dealing with sensitive and challenging issues faced by practicing rheumatology nurses and nurse practitioners in a clinically-meaningful manner Survey cohort participants showed a substantial improvement in their understanding of a variety of rheumatic diseases and improved their ability to communicate with patients about disease diagnosis and treatment options. References [1] Rheumatology Nurse Practice. New Insights into the Treatment of the Spondyloarthropathies. Volume 3, Issue 5. [2] Rheumatology Nurse Practice. Looking at the Horizon: What Does the Future Hold in the Treatment of Rheumatoid Arthritis? Volume 3, Issue 6. [3] Rheumatology Nurse Practice. The Pathophysiology of Spondyloarthritis: Connecting and Differentiating Characteristics. Volume 3, Issue 7. [4] Rheumatology Nurse Practice. The Pathophysiology of Systemic Lupus Erythematosus: A Nursing Primer. Volume 3, Issue 8. Acknowledgement Audience generation and production assistance was provided by Lyons Den Solutions Disclosure of Interests Linda Grinnell-Merrick Consultant for: Abbvie, Celgene, Lily, Pfizer, Sanofi, Speakers bureau: Abbvie, Celgene, Janssen, Novartis, Sanofi, Iris Zink Consultant for: Pfizer, Speakers bureau: AbbVie, Crescendo Biosciences, Horizon, Elizabeth Kirchner Consultant for: Celgene, Regeneron, Speakers bureau: Merck, Regeneron, Jacqueline Fritz Consultant for: Lilly, AbbVie, Celgene, Horizon, Momenta Pharmaceuticals, Speakers bureau: Celgene, AbbVie, Genentech, Horizon, Monica Richey Consultant for: Celgene, Novartis, Speakers bureau: Mallinckrodt, Cathy Patty-Resk: None declared, Carrie Beach Consultant for: Celgene, Merck, Sanofi, Vickie Sayles Consultant for: Celgene, Eileen McCullagh Shareholder of: Abbott, AbbVie, Amgen, Baxalta, Baxter, BMS, Pfizer, Eileen Lydon Consultant for: Celgene, Horizon, Sanofi, Speakers bureau: AbbVie, Novartis, Sheree Carter: None declared, Scott Kober: None declared

Background The management of gout can be problematic in the hospital setting; hospitalised patients usually have significant comorbidities and receive multiple medications which leads to a high frequency of contraindications to established gout therapies. We have previously shown the ACTH is a safe and fast acting therapeutic option for acute gout in hospitalised patients in a large scale retrospective study.1 Objectives To directly compare the efficacy of ACTH vs betamethasone for the treatment of acute gout in hospitalised patients in a prospective manner. Methods Hospitalised patients with acute gout, fulfilling the ACR criteria, were treated with an IM injection of either 100 IU of ACTH (Synachten Depot) or 6 mg of betamethasone (Celestone Chronodose-the most widely use IM steroid formulation in our country) on an alternate 1/1 basis. Clinical efficacy was assessed at 24, 48, 72 hour and 5 days as follows: a) Intensity of pain using a Visual Analogue Scale (VAS 0–10), b) physician global assessment (0–10) and c) swelling, redness and warmth (0–3 scale). Pain VAS was also self reported by the patient at 6 and 12 hour. Comorbidities representing contraindications to established gout therapies were recorded. Primary outcome of the study was the change in pain VAS at 24 and 48 hour. Secondary outcomes were changes in physician global assessment and changes in objective signs of inflammation. Results This is a 6 month interim analysis of an ongoing investigator initiated clinical study. Twelve patients (8 male) with a mean ±SD of 66.9±12.3 years were recruited and treated with ACTH or betamethasone on an alternate basis (6 in each treatment group). In most cases (n=11) the attack was monoarticular. The majority of patients had multiple comorbidities with the commonest being hypertension (9/12). Both treatments were effective. ACTH led to a significant decline in pain VAS at 24 hour compared to baseline (mean ±SEM: 2.33±1.21 vs 7.66±0.81 respectively, p=0.0002) and at 48 hour (1.40±1.14, p=0.0011 compared to baseline). Betamethasone was also effective with an improvement in pain VAS at 24 hour compared to baseline (mean ±SEM: 1.83±0.98 vs 5.33±2.16 respectively, p=0.0024) and at 48 hour (0.75±0.95, p=0.02 compared to baseline). However, direct comparison between treatment arms showed that ACTH treated patients exhibited a higher change in pain VAS at 24 hour compared to betamethasone treated patients (mean ±SEM: 5.5±0.5 vs 3.5±0.61 respectively, p=0.03). At the 48 hour time point ACTH treated patients still showed a higher change in pain VAS (mean ±SEM: 6.4±0.6 vs 4±0.91 respectively, p=0.056). A trend favouring ACTH was already evident at the 12 hour time point; the change in pain VAS was 4±1.54 vs 3.1±1.47 for ACTH vs betamethasone, respectively, p=ns). No changes in physician global assessment and objective signs of inflammation was found at 24 and 48 hour between treatment groups. Treatment was well tolerated in both groups. Conclusions Both steroids and ACTH are effective in the treatment of gout in hospitalised patients but ACTH is faster acting. ACTH may be an attractive therapeutic choice in patients with multiple comorbidities that cannot receive standard treatment. References [1] Daoussiset al, Joint Bone Spine, 2013 Disclosure of Interest P. Kordas: None declared, I. Antonopoulos: None declared, D. Velissaris: None declared, D. Daoussis Speakers bureau: Mallinckrodt Pharmaceuticals

Background Psoriatic arthritis (PsA) is associated with joint inflammation, characterised by synovitis, presence of erosions, joint space narrowing (JSN) and new bone formation leading to structural damage, increased disability and reduced quality of life. Secukinumab (SEC) provided significant and rapid clinical efficacy, and inhibition of radiographic progression in PsA patients (pts) in the FUTURE 5 study.1 Objectives To assess the effect of subcutaneous (sc) SEC on radiographic progression by prior anti–TNF therapy or concomitant methotrexate (MTX) use in the FUTURE 5 study. Methods Adults (n=996) with active PsA, stratified by prior anti–TNF therapy (naive and inadequate response/intolerance [IR]) were randomised 2:2:2:3 to sc SEC 300 mg with loading dose (LD), 150 mg LD, 150 mg no LD, or placebo (PBO) at baseline (BL), Wks 1, 2, 3, 4, and every 4 wks thereafter.1 At Wk 16, PBO non-responders were switched to SEC 300 or 150 mg. Concomitant MTX (≤25 mg/week) was allowed. Radiographic progression (mean change in van der Heijde-modified total Sharp score for PsA [vdH-mTSS] and its components: erosion and joint space narrowing [JSN] scores from BL to Wk 24) was based on hand/wrist/foot X-rays obtained at BL, Wks 16 (non-responders) assessed by two blinded readers (plus an adjudicator if required). Average scores were used. Statistical analyses used linear extrapolation at Wk 24 for all PBO non-responders and for all other pts with missing Wk 24 X-rays. Results At BL, 30% pts were anti–TNF-IR and 50% were on concomitant MTX. Radiographic progression was significantly inhibited at Wk 24 in the overall population with SEC vs PBO; mean change from BL in vdH-mTSS was 0.08 (300mg; p Conclusions Subcutaneous secukinumab 300 mg with loading dose, and 150 mg with and without loading dose, inhibited radiographic progression in patients with active PsA. Low rates of radiographic progression were observed regardless of previous anti-TNF therapy or concomitant MTX use. Reference [[1] ] ] Mease PJ, et al. Arthritis Rheumatol2017;69(suppl 10). Disclosure of Interest D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB, Employee of: Director of Imaging Rheumatology, P. Mease Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Covagen, Crescendo, Janssen, LEO, Lilly, Merck, Novartis, Pfizer, SUN, and UCB; speakers’ bureau for AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Pfizer, and UCB, R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth, Employee of: Director of Rheumatology Consultancy BV, Speakers bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, P. Rahman Consultant for: Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer and Roche, pharmaceutical companies dealing with biologic agents in Rheumatology, H. Tahir Grant/research support from: Novartis, Pfizer, Consultant for: Abbvie, Novartis, Pfizer, UCB, Eli-Lilly, Janssen, A. Singhal Grant/research support from: AbbVie, Gilead, Sanofi, Regeneron, Amgen, Roche, BMS, Janssen, Lilly, Novartis, Pfizer, UCB, Astra Zeneca, MedImmune, FujiFilm, Nichi-Iko, Mallinckrodt, Speakers bureau: AbbVie, E. Boettcher Consultant for: Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis, Speakers bureau: Amgen, Roche, Eli Lilly, Pfizer, MSD, Novartis, S. Navarra Consultant for: Pfizer, Novartis, Astra-Zeneca, Janssen, Astellas, Roche, Speakers bureau: Pfizer, Novartis, Astra-Zeneca, Janssen, Astellas, Roche, X. Zhu Employee of: Novartis, A. Readie Shareholder of: Novartis stock, Employee of: Novartis, L. Pricop Shareholder of: Novartis stock, Employee of: Novartis, K. Abrams Shareholder of: Novartis stock, Employee of: Novartis

Background: Rheumatoid arthritis (RA) is an autoimmune disorder associated with chronic inflammation and is treated with disease-modifying anti-rheumatic drugs (DMARDs) for active disease. Both American College of Rheumatology (ACR) and EULAR recommend that short-term administration of corticosteroids (CSs) may be beneficial for its anti–inflammatory effects. Repository corticotropin injection (RCI) is a complex mixture containing purified porcine pituitary adrenocorticotropic hormone (ACTH)-analogue and an agonist for all 5 melanocortin receptors (MCRs). Activation of MCRs by ACTH has been shown to have direct and indirect anti–inflammatory and immunomodulatory effects. RCI is approved in the United States as adjunctive therapy for short–term administration in RA. Objectives: To present interim data after 100% enrollment from the initial 12-week open-label phase of a multicenter, 2–part study evaluating the efficacy, safety, and appropriate duration of RCI therapy in patients with persistently active RA despite receiving 1 or 2 DMARDs and/or CSs. Methods: In the open–label period (Part 1, Weeks 0–12), all enrolled patients received RCI 1 mL (80 U SC) twice weekly for 12 weeks. Patients who achieved low disease activity (LDA; DAS28-ESR score Results: 259 patients had enrolled, 235 had completed and 24 had discontinued the 12-week open-label period of the study; 88.9% were female and mean age was 51 years. RCI treatment resulted in 62.5% of patients achieving LDA at Week 12; results for this interim analysis are presented in the Table. Bone turnover markers were stable from baseline to Week 12, indicating no effect of RCI on bone metabolism. 98 (37.8%) patients reported adverse events (AEs) with 3 (1.2%) patients reporting serious AEs (ie, non–cardiac chest pain, pneumonia, and craniocerebral injury). The most common AEs were urinary tract infection (n=10), headache (n=9), and pharyngitis (n=7). Conclusion: In the 12-week open label period of this study, RCI appeared to be generally safe and effective in patients with persistently active RA who were nonresponsive to DMARDs and CSs. This was demonstrated by improvement in multiple measures of disease activity. Further results will be evaluated in Part 2 of the study. Acknowledgement: Editorial support was provided by MedLogix Communications, LLC, Itasca, Illinois, under the direction of the authors and was funded by Mallinckrodt ARD LLC. Disclosure of Interests: Roy Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Dan Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS Corbus, NIH, Novartis, Pfizer, Roche/Genentech, Consultant for: AbbVie, Actelion, Amgen, BMS, Cytori, Novartis, Pfizer, Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), Jingyu Liu Shareholder of: Mallinckrodt ARC, LLC, Employee of: Mallinckrodt ARC, LLC, Julie Zhu Shareholder of: Mallinckrodt ARC, LLC, Employee of: Mallinckrodt ARC, LLC, Erin Connolly-Strong Shareholder of: Mallinckrodt ARC, LLC, Employee of: Mallinckrodt ARC, LLC, Richard Brasington: None declared

Background Adalimumab is an anti–tumour necrosis factor-α (TNF-α) agent indicated for the treatment of immune-mediated diseases. The long-term safety of adalimumab was previously reported in 23 458 patients representing up to 12 years of clinical trial exposure in rheumatoid arthritis (RA), juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis (PsA), plaque psoriasis (Ps), and Crohn’s disease (CD). Objectives Here we report an updated analysis examining the long-term safety of adalimumab in adult patients with RA, AS, non-radiographic axial spondyloarthritis (nr-axSpA), peripheral SpA (pSpA), PsA, Ps, hidradenitis suppurativa (HS), CD, ulcerative colitis (UC), and non-infectious uveitis (UV). Methods Here we report an updated analysis examining the long-term safety of adalimumab in adult patients with RA, AS, non-radiographic axial spondyloarthritis (nr-axSpA), peripheral SpA (pSpA), PsA, Ps, hidradenitis suppurativa (HS), CD, ulcerative colitis (UC), and non-infectious uveitis (UV). Results This analysis included 29 987 patients, representing 56 951 patient-years of exposure (table 2). The majority of adalimumab exposure was in RA studies. The most frequently reported SAE of interest was infection (highest incidences in CD, RA, UV, and UC). Overall and for most of the adalimumab populations (AS, PsA, Ps, UC, CD, and RA), the observed number of deaths was below what would be expected in an age- and sex–adjusted population (table 1). For HS, nr-axSpA, pSpA, and UV studies, the small size of these trials precluded accurate assessment of the standardised mortality ratio, and the 95% CIs all included 1.0. Conclusions This analysis of data from clinical trials of adalimumab demonstrated an overall safety profile consistent with previous findings and with the TNF inhibitor class. No new safety signals or tolerability issues with adalimumab treatment were identified and, for most indications, the mortality rate was below what would be expected in an age- and sex–adjusted population. Efficacy and safety data continue to support the well-established benefits of adalimumab for the approved indications. Acknowledgements AbbVie funded the study, contributed to its design, and participated in data collection, analysis and interpretation of the data, and in writing, review, and approval of the publication. Medical writing (funded by AbbVie): Maria Hovenden, PhD, and Janet Matsuura, PhD, of CPS. Disclosure of Interest G. Burmester Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and UCB, R. Panaccione Grant/research support from: Abbott Laboratories, Axcan, Bristol-Myers Squibb, Centocor, Elan, Millenium, and Procter and Gamble; honoraria from Abbott Laboratories, AstraZeneca, Byk Solvay, Centocor, Elan, Janssen, Procter and Gamble, Prometheus, Schering-Plough, and Shire, Consultant for: Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Centocor, Elan, Ferring, GlaxoSmithKline, Procter and Gamble, Schering-Plough, Shire, and UCB, K. Gordon Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, and Janssen, Consultant for: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, and Pfizer, J. Rosenbaum Shareholder of: Royalties: UptoDate, Grant/research support from: Alcon Research Institute, Consultant for: Abbvie, Gilead, Santen, Regeneron, UCB, Cavtherx, Portage, Eyevensys, and Stem Cell Inc, Speakers bureau: Mallinckrodt, D. Arikan Shareholder of: AbbVie, Employee of: AbbVie, W. Lau Shareholder of: AbbVie, Employee of: AbbVie, R. Tarzynski-Potempa Shareholder of: AbbVie, Employee of: AbbVie

Background Tofacitinib is anoral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives This post hoc analysis aims to explore the efficacy of tofacitinib in patients (pts) with RA based on their baseline (BL) body mass index (BMI). Methods Data were analysed from six Phase 3 studies for pts who were methotrexate-naive (NCT01039688) or had an inadequate response to DMARDs (NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385) and received ≥1 dose of tofacitinib 5 or 10 mg twice daily (BID) or placebo (PBO). Pts were stratified by BL BMI ( Results Overall, 1589, 1611 and 681 pts received tofacitinib 5 and 10 mg BID and PBO, respectively, with 1690, 1173 and 1017 pts in the BMI Conclusions Results of this post hoc analysis suggest that tofacitinib is associated with improvements in RA outcomes compared with PBO regardless of BL BMI category. In both tofacitinib and PBO groups, similar trends in improvements were seen in most endpoints regardless of BMI category, implying that the effect of BL BMI is not specific to tofacitinib. Further investigation is needed to assess the degree of impactof BMI on tofacitinib efficacy. Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by C Viegelmann of CMC and funded by Pfizer Inc. Disclosure of Interest: A. DikranianGrant/research support from: AbbVie, Mallinckrodt, Pfizer Inc, Speakers bureau:AbbVie, Amgen, Celgene, Mallinckrodt, Pfizer Inc, M. Gonzalez-Gay Consultant for: Pfizer Inc, F. Wellborne Grant/research support from: AbbVie, BMS, EliLilly, Novartis, Pfizer Inc, Sanofi/Genzyme/Regeneron, Consultant for: AbbVie,BMS, Novartis, Pfizer Inc, Sanofi/Genzyme/Regeneron, Speakers bureau: AbbVie,BMS, Eli Lilly, Novartis, Pfizer Inc, Sanofi/Genzyme/Regeneron, J.Alvaro-Gracia Consultant for: Abbvie, BMS, Eli Lilly, MSD, Novartis, PfizerInc, Roche, Sanofi/Genzyme/Regeneron, Speakers bureau: Abbvie, BMS, Eli Lilly,MSD, Novartis, Pfizer Inc, Roche, Sanofi/Genzyme/Regeneron, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Chapman Shareholder of: Pfizer Inc,Employee of: Pfizer Inc, S. Tatulych Shareholder of: Pfizer Inc, Employee of:Pfizer Inc, P. Dahl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J.Curtis Grant/research support from: Amgen, Corrona, Crescendo Bio, Pfizer Inc, Consultant for: AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Roche/Genentech,UCB

Background Strong genetic association has been reported between RA and human leukocyte antigen (HLA) regions, particularly HLA-DRB1 alleles with the shared epitope (SE). SE alleles are associated with seropositivity, erosions and higher disease activity (DA) in RA. Objectives To evaluate the association between SE alleles and the presence of multiple poor prognostic factors (PPFs) of seropositive (anti-citrullinated protein antibody [ACPA] and/or RF) and erosive RA; as well as changes in DA. Methods We analysed patients (pts) enrolled in a large sequential RA registry established in 2003; most had established RA and annual clinical evaluations. Pts with baseline (BL) data on SE status were included. A commercially available kit (Qiagen, USA) was used for HLA genotyping. HLA-DRB1 serotypes were assessed from DNA sequences using allele-specific polymerase chain reaction methods and categorised as pts with no, 1 or 2 SE alleles. Changes from BL were compared in pts with vs without SE alleles. The association of multiple PPFs and SE status was evaluated using multinomial logistic models. The association between change in DA and SE status was analysed using linear regression models with age, sex, disease duration (DD), co-morbidities and biologic DMARDs as covariates. Results Of 689 RA pts included, no, 1 and 2 SE alleles were reported in 241 (35.0%), 275 (40.0%) and 173 (25.1%) pts, respectively. At BL, pts with SE alleles (vs no SE) were more likely to have PPFs, and had longer DD and higher DA (table 1). The odds ratio (OR) for seropositive erosive RA in pts with 2 and 1 SE alleles (vs no SE) was 5.44 (95% CI 2.39, 12.39) and 2.87 (1.32, 6.23; Fig), respectively. The OR for double seropositivity in pts with 2 and 1 SE alleles (vs no SE) was 4.27 (95% CI 2.51, 7.28) and 2.56 (1.66, 3.94), respectively. A total of 551 pts had DA measures at BL and 1 year follow-up. After controlling for BL covariates, pts with SE (vs no SE) had an average increase in DAS28 (CRP) of 0.24 (p=0.031), CDAI of 2.71 (p=0.027) and SDAI of 3.25 (p=0.013; Table 2). Conclusions Pts with (vs without) SE alleles are more likely to have multiple PPFs; pts with 2 SE alleles are 5 times more likely to be seropositive with erosive RA and 4 times more likely to be double positive. Pts with (vs without) SE alleles also experienced an increase in DA over time with standard-of-care treatment. Disclosure of Interest E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Z. Guo Employee of: Bristol-Myers Squibb, J. Bryson Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, C. Iannaccone: None declared, M. Frits: None declared, N. Shadick Grant/research support from: BRASS registry, Amgen, Bristol-Myers Squibb, and Mallinckrodt, Consultant for: Bristol-Myers Squibb, M. Weinblatt Grant/research support from: Bristol-Myers Squibb, Amgen, Crescendo Bioscience, Sanofi, Consultant for: Bristol-Myers Squibb, Amgen, Crescendo Bioscience, AbbVie, Eli Lilly, Pfizer, Roche, Merck, Samsung, Novartis

Background The MBDA score, based on 12 serum proteins, is a validated tool for assessing disease activity in RA patients. MBDA biomarkers may be influenced by age, sex and adiposity. Objectives To develop and validate an adjusted MBDA score that accounted for these three factors, using BMI or serum leptin as proxies for adiposity. Methods The MBDA score as a continuous variable was adjusted to account for age, sex and a proxy for adiposity (serum leptin) using data from 325,781 RA patients for whom MBDA tests had been ordered as part of routine care. Leptin values came from the MBDA test. As an alternative to using leptin to adjust for adiposity, a cohort of 1411 patients from 5 studies/registries (BRASS, Corrona-CERTAIN, InFoRM, OPERA, RACER) was used to adjust for BMI, which was not available in the larger cohort, adding this BMI adjustment to that for age/sex from the larger cohort. Both types of adjusted MBDA score use the low, moderate, and high disease activity cutpoints of the original MBDA score. The two adjusted MBDA scores and other variables were evaluated for the prediction of radiographic progression (RP) in the 2 cohorts with available data (OPERA, BRASS) using univariate and multivariate linear regression analyses. Rate of RP was assessed as the change in modified total Sharp score (ΔmTSS) per year after MBDA testing. Results The MBDA score increased with age, BMI and leptin concentration. In univariate analysis of the combined OPERA and BRASS cohorts (n=555), the significant variables predicting ΔmTSS were leptin-adjusted MBDA score, seropositivity for RF or anti-CCP, BMI-adjusted MBDA score, MBDA score, BMI, CRP, baseline mTSS, disease duration, DAS28-CRP, SDAI, CDAI and DAS28* (table 1). The leptin- and BMI-adjusted MBDA scores were the first and third most significant univariate predictors of ΔmTSS. To compare them directly, DAS28-CRP, MBDA score, BMI-adjusted MBDA score and leptin-adjusted MBDA score were combined in pairs in regression analyses of ΔmTSS; the BMI-adjusted (p=0.0027) and leptin-adjusted MBDA score were significant (p=0.00063) after adjusting for DAS28-CRP (p=0.87 and 0.74, respectively) and the leptin-adjusted MBDA score was significant (p=0.024 and 0.020, respectively) after adjusting for either the MBDA (p=0.32) or BMI-adjusted MBDA scores (p=0.094). Conclusions We developed two adjusted MBDA scores that combine molecular and biometric variables to account for age, sex, and adiposity. The leptin-adjusted MBDA score, significantly outperformed DAS28-CRP and the original MBDA score in predicting radiographic progression in RA patients. These results suggest that the leptin-adjusted MBDA score may offer improved clinical utility for the personalised management of patients with RA. Disclosure of Interest J. Curtis Grant/research support from: Crescendo Bioscience Inc., Consultant for: Crescendo Bioscience Inc., D. Flake II Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience Inc., UCB, and Genzyme, Consultant for: Amgen, Bristol-Myers Squibb, Crescendo Bioscience Inc., UCP, and Genzyme, N. Shadick Grant/research support from: Bristol-Myers Squibb, Consultant for: Mallinckrodt, Amgen, Bristol-Myers Squibb, UCB, DxTerity, Sanofi, Crescendo Bioscience Inc., Janssen, and Merck, M. Ostergaard Grant/research support from: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Novartis, Orion, Pfizer, Regeneron, Roche, Takeda, and UCB, Consultant for: AbbVie, BMS, Celgene, Crescendo Bioscience Inc., Janssen, and Merck, M. Hetland Consultant for: AbbVie, Biogen, BMS, CelltrionRoche, Crescendo Bioscience Inc., Eli Lilly, MSD, Pfizer, and UCB, Speakers bureau: Orion, C. Heegaard Brahe: None declared, Y. Hwang Consultant for: Pfizer Inc., D. Furst: None declared, V. Strand Grant/research support from: Abbvie, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo Bioscience Inc., EMDSerono, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Protagen, Regeneron, Samsung, Sandoz, Sanofi, and UCB, C. Etzel Shareholder of: CORRONA, LLC, Grant/research support from: Merck, Employee of: CORRONA, LLC, D. Pappas Shareholder of: CORRONA, LLC, Employee of: CORRONA, LLC, Paid instructor for: Novartis Pharmaceutical, X. Wang Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., C. Hwang Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., E. Sasso Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., A. Gutin Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., E. Hitraya Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., J. Lanchbury Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc.

Background Previous studies showed that RF positivity (+) in RA was associated with increased overall mortality, and that cause-specific mortality rates differed by autoantibodies. Anti-citrullinated protein antibodies (ACPAs) have been associated with cardiovascular death, and RF with death due to neoplasm and respiratory disease. 1 Objectives To evaluate the association of serostatus (in particular, antibody [Ab] titres) with mortality and its modification by DMARDs. Methods Administrative claims data from Optum Clinformatics Data Mart and Humana databases (2006–2016) were used. Inclusion criteria: 2 diagnosis codes for RA plus 1 DMARD prescription; age ≥18 years (y);≥6 months (M) baseline (BL;+/–3 M from index date). Index date was the first test date for ACPA or RF (main analysis) or the DMARD prescription date (DMARD effect on mortality analysis). Patients (pts) with ankylosing spondylitis, Crohn’s disease, lupus, psoriatic arthritis or ulcerative colitis at/before index date were excluded. Based on BL Ab test, pts were categorised into Ab status of ACPA+/–, RF +/–and double +/–. Ab +pts were then categorised into 2 groups based on Ab titres. DMARD-exposed pts were categorised into biologic (b)DMARD (use of any bDMARD) and conventional (c)DMARD (use of a cDMARD but never a bDMARD) cohorts. Crude mortality rates per 1000 pt-y, as well as adjusted analysis using traditional multivariate regression and disease risk score methods, were used. Covariates were age, sex, region, physician office visits in past 3 M, indicator variable for RA diagnosis before ACPA/RF testing, past hospitalisation, medication use (steroids, NSAIDs, salicylates), DMARD use and co-morbidities. Results A total of 53 849 and 79 926 pts with RA had evaluable ACPA and RF status, respectively. The average (SD) age was 61.4 (15.2) and 61.8 (15.6) y in the ACPA and RF cohorts, respectively. For both ACPA and RF, mortality rates were significantly higher in Ab +vs Ab– pts, and were highest in pts with the highest Ab titres (table 1). The hazard ratios (HRs) for mortality were highest in pts with double positivity (figure 1A). HRs were higher in Ab +vs Ab– pts exposed to cDMARDs. There was no difference in mortality between Ab +vs Ab– pts in the bDMARD-exposed group (figure 1B). Conclusions Elevated ACPA and RF titres were independently associated with increased mortality among pts with RA. The associations between ACPA/RF and mortality persisted in those treated with cDMARDs but not with bDMARDs. Further studies are warranted to evaluate the effect of bDMARDs on mortality in seropositive pts. Reference [1] Ajeganova S, et al. Ann Rheum Dis2016;75:1924–32. Disclosure of Interest E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Z. Guo Employee of: Bristol-Myers Squibb, M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Sanofi, Consultant for: Amgen, Bristol-Myers Squibb, Crescendo Bioscience, AbbVie, Lilly, Pfizer, Roche, Merck, Samsung Novartis, N. Shadick Grant/research support from: BRASS registry, Amgen, Bristol-Myers Squibb, and Mallinckrodt, Consultant for: Bristol-Myers Squibb

Background Compared to the general population, RA patients (pts) are less likely to be employed and have lower HRQoL.1,2 However, data on impact of work status on HRQoL in RA pts are limited. Objectives Evaluate association between work status and HRQoL in RA pts. Methods We analysed data from adult pts enrolled in a large sequential RA registry. Physicians assessed pt demographics, clinical characteristics, disease activity and laboratory parameters at baseline (BL) and then annually. Follow-up questionnaires to assess pt-reported outcomes were administered every 6 months and included HRQoL measures (12-Item Short-Form Health Survey physical and mental component summary [SF-12 PCS, MCS], EuroQoL-5 Dimension [EQ-5D]) and work status; higher score indicates better health for all 3 HRQoL measures. General linear mixed models with repeated measures were used for SF-12 analysis and finite mixture models for the EQ-5D analysis, controlling for BL covariates. Results A total of 974 RA pts with HRQoL information were included: 49.3% (n=480) ‘employed for pay’, 38.9% (n=379) ‘employed not for pay’ (retired, homemaker or student), 11.8% (n=115) ‘not employed or on disability’. Pts employed for pay were younger and had lower disease activity compared with other groups (table 1). Compared with pts ‘not employed or on disability’, pts employed had significantly higher PCS (mean [SE] 7.17 [0.82]; p Conclusions Work status and household income in RA are independently associated with HRQoL. More studies are needed to evaluate impact of work on changes in HRQoL in RA pts. References [1] Uhlig T, et al. J Rheumatol2007;34:1241–7. [2] Chorus AM, et al. Ann Rheum Dis2003;62:1178–84. Disclosure of Interest E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Boonen: None declared, Z. Guo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, C. Iannaccone: None declared, M. Frits: None declared, M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Lilly, Merck, Novartis, Pfizer, Roche, Samsung, N. Shadick Grant/research support from: Amgen, BRASS registry, Bristol-Myers Squibb, Mallinckrodt, Consultant for: Bristol-Myers Squibb

Background Prior studies have demonstrated challenges in developing and validating claims-based algorithms that accurately predict RA disease activity.1 2 The ability to adjust for and predict RA disease activity would be a powerful epidemiological tool for studies that lack direct disease activity measures such as the DAS28. Objectives We used machine-learning methods to incorporate claims and electronic medical record (EMR) data to develop models to predict DAS28 (CRP) as a continuous measure, and to distinguish moderate-to-high disease activity from low activity/remission. Methods We identified 300 adults (≥18 years of age) with RA enrolled in a single academic centre cohort with ≥1 year of linked Medicare insurance claims preceding a DAS28 (CRP) measurement between 2006 and 2010. Of these, 95 had Medicare Part D pharmacy data. From claims we included demographics, co-morbidities, joint replacement surgery, physical therapy visits, numbers of RA-related codes, laboratory values and imaging studies, and healthcare utilisation. For those with Part D pharmacy data we included medications (steroids, analgesics, DMARDs) and switches between drugs. From the EMRs we obtained smoking status, BMI, blood pressure, medication use, laboratory values for seropositivity (RF or anti-cyclic citrullinated peptide antibodies), haematocrit, ESR and CRP. We constructed models with claims only, claims with medications and claims with EMR data. We examined these models with DAS28 (CRP) as a continuous measure and as a binary outcome (moderate/high activity vs low activity/remission). We used adaptive least absolute shrinkage and selection operator (LASSO), which avoids model overfitting by penalising large coefficients and selects a subset of variables by shrinking some coefficients to zero. We used adjusted R2 to compare continuous model fit and C-statistics to compare binary models. Results In models that included DAS28 as a continuous measure, using claims alone explained 11% of the DAS28 variability. Adding medications and EMR data to claims improved the adjusted R2 by 6% (table 1). In models that included DAS28 as a binary outcome (moderate/high activity vs low activity/remission), our claims-only model yielded a C-statistic of 0.68, which increased to 0.79 after inclusion of medications and EMR data. Conclusions Incorporating medications, EMR data and laboratory values into a claims-based index did not significantly improve the ability to predict DAS28 scores as a continuous measure. However, models that include claims, medications and EMR data may be used to reasonably distinguish moderate-to-high disease activity from low disease activity/remission. References [1] Sauer BC, et al. Arthritis Res Ther2017;19:86. [2] Desai RJ, et al. Arthritis Res Ther2015;17:83. Disclosure of Interest C. Feldman Grant/research support from: Bristol-Myers Squibb, Pfizer, K. Yoshida Grant/research support from: Tuition support from Harvard T.H. Chan School of Public Health (partially supported by training grants from Pfizer, Takeda, Bayer and PhRMA)., B. Pan: None declared, M. Frits: None declared, N. Shadick Grant/research support from: BRASS registry, Amgen, Bristol-Myers Squibb, and Mallinckrodt, Consultant for: Bristol-Myers Squibb, M. Weinblatt Grant/research support from: Bristol-Myers Squibb, Amgen, Crescendo Bioscience, Sanofi, Consultant for: Bristol-Myers Squibb, Amgen, Crescendo Bioscience, AbbVie, Eli Lilly, Pfizer, Roche, Merck, Samsung, Novartis, S. Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, D. Solomon Grant/research support from: Bristol-Myers Squibb, Pfizer, Amgen, Genentech

Background Ixekizumab (IXE), a high-affinity monoclonal antibody selectively targeting interleukin-17A, significantly improved fingernail psoriasis by Week (Wk) 12 vs placebo (PBO) in patients (pts) with moderate-to-severe plaque psoriasis 1 . Moreover, IXE had significantly reduced signs and symptoms of psoriatic arthritis (PsA) at Wk 24 in biologic disease-modifying antirheumatic drug (bDMARD)-naive pts with active PsA 2 . Objectives To evaluate the impact of IXE on nail and skin lesions in active PsA pts who have previously received bDMARD therapy. Methods In this phase 3, multicentre, double-blind, PBO-controlled, outpatient study, pts (aged ≥18 years) with active PsA and bDMARD-experience randomly (1:1:1) received PBO for 24 Wks, 80 mg IXE as one injection every 2 (IXE Q2W) or 4 Wks (IXE Q4W) after starting dose of 160 mg. At Wk 16, inadequate responders received rescue medication and PBO pts were re-randomised (1:1) to receive either IXE Q2W or IXE Q4W. The efficacy of IXE was assessed by Nail Psoriasis Severity Index (NAPSI) in pts with nail psoriasis at baseline (PBO, n=73; IXE Q4W, n=89; IXE Q2W, n=74), Psoriasis Area and Severity Index (PASI) 75/90/100 response rate at Wk24 in pts with baseline body surface area (BSA) ≥3 (PBO, n=67; IXE Q4W, n=68; IXE Q2W, n=68) and percentage of pts achieving static Physician Global Assessment (sPGA) of psoriasis score of 0 (cleared) or 1 (minimal) in pts with baseline sPGA≥3 (PBO, n=55; IXEQ4W, n=60; IXEQ2W, n=62). Missing data and inadequate responder data were imputed using the nonresponder imputation for categorical variables. For continuous variables, least squares mean (LSM) changes were calculated using mixed effects models for repeated measures, observed data from Wks 16 to 24 was excluded for inadequate responders. Results Overall the demographics and baseline characteristics were comparable between the treatment groups. The mean (SD) NAPSI total score at baseline was 19 (19), 20 (20), and 21 (22) in PBO, IXE Q4W and IXE Q2W, respectively. At Wk 24, the change in NAPSI total score from baseline was significantly greater with IXE Q4W (LSM±SE -10.2±2.04) and IXE Q2W (-10.8±2.12) vs PBO (0.5±2.13, p Conclusions In the present study, ixekizumab led to significantly greater reduction and clearance of the nail and skin lesions in active PsA pts who had previously received bDMARD therapy compared to placebo. References Dennehy EB et al. J Drugs Dermatol. 201615(8):958–61. Mease PJ, et al. Ann Rheum Dis. 2016 doi: 10.1136/annrheumdis-2016–209709. Disclosure of Interest L. Kristensen Grant/research support from: UCB, Janssen-Cilag and Biogen, Consultant for: Pfizer, AbbVie, Amgen, UCB, Celegene, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Speakers bureau: Pfizer, AbbVie, Amgen, Biogen, UCB, Celegene, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, J. Merola Grant/research support from: Biogen IDEC, Consultant for: Biogen IDEC, Amgen, AbbVie, and Eli Lilly, Novartis, Pfizer, Janssen, UCB, Kiniksa, Momenta and Mallinckrodt, J. Dutz Grant/research support from: Abbvie, Novartis, Amgen, Consultant for: Cipher, Speakers bureau: Janssen, Abbvie, Novartis, Amgen, Leo, Celgene, D. Adams Employee of: Eli Lilly and Company, L. Kerr Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, P. Rich Grant/research support from: UCB, Janssen-Cilag and Biogen, Consultant for: Pfizer, AbbVie, Amgen, UCB, Celegene, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Speakers bureau: Pfizer, AbbVie, Amgen, Biogen, UCB, Celegene, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals.

Background High anti-citrullinated protein antibody (ACPA) concentration, beyond ACPA positivity, is indicative of more aggressive radiographic progression in patients (pts) with RA. 1 However, there is limited information on changes in ACPA levels in clinical practice settings, and the association of changes in ACPA with measures of resource use and/or disease activity. Objectives To evaluate the association between change in ACPA levels with hospitalizations/durable medical equipment (DME) use and change in disease activity. Methods Pts enrolled in a tertiary care centre RA registry, established in 2003, were analysed. The registry mostly comprises pts with established RA who were evaluated semi-annually for multiple clinical patient-reported outcomes as well as resource utilization parameters, and annually for disease activity measures such as DAS28 (CRP), SDAI and CDAI. The current analysis is based on pts enrolled in the registry with ACPA values at the time of baseline (BL) and follow-up visits. BL and follow-up ACPA levels were based on well-documented and validated ELISAs from Euro-Diagnostica (distributed by IBL-America, Minneapolis, MN, USA). Annual mean ACPA change from BL over the first year of enrolment in the registry was calculated. Changes ([follow-up – BL]/BL x 100) in ACPA levels were categorized as decrease ( +10%). Use of DME (canes, wheelchairs, walkers and commodes) as well as hospitalizations during 12-month follow-up and annual change in disease activity (DAS28 [CRP], SDAI, CDAI, swollen painful joint counts and pain) were assessed. Multivariate logistic regression analyses for binary outcome variables (DME and hospitalizations) and linear regression for change in disease activity measures were conducted, controlling for BL covariates. Results A total of 840 (65%) pts in the registry had BL and follow-up ACPA values and were included in the analysis. Overall, 34.6% (n=291) of pts had a decrease, 31.7% (n=266) had no change and 33.7% (n=283) had an increase in ACPA levels. There were no significant differences in BL characteristics between the three groups except for disease duration. Pts with RA with an increase in ACPA levels had significantly longer disease duration at BL. In univariate analyses, DME use was 23.4%, 30.1% and 28.6%, and hospitalization rate was 13.4%, 16.5% and 20.1% in pts with a decrease, no change or an increase in ACPA levels, respectively. Unadjusted mean (SD) change from BL in DAS28 (CRP), SDAI and CDAI in pts with reductions in ACPA levels was –0.7 (1.4), –6.1 (15.7) and –5.9 (15.1), and –0.5 (1.4), –5.0 (15.7) and –4.7 (14.6) in pts with an increase in ACPA levels. After controlling for BL covariates, the odds ratio (OR) for DME in patients who had a decrease in ACPA levels (vs increase) was 0.62 (95% CI 0.40, 0.94; p=0.026), and the OR for hospitalization was 0.54 (0.33, 0.86; p=0.010). Similarly, reductions in ACPA levels were associated with greater reductions in disease activity measures (Fig). Conclusions Reductions in ACPA levels were associated with reductions in DME use and hospitalizations as well as reductions in disease activity measures. References Ronnelid J, et al. Ann Rheum Dis 2005;64:1744–9. Disclosure of Interest E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Z. Guo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, C. Iannaccone: None declared, M. Frits: None declared, N. Shadick Grant/research support from: Bristol-Myers Squibb, UCB, Mallinckrodt, Amgen, Crescendo Biosciences, Consultant for: Bristol-Myers Squibb, M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo, UCB, Dxterity, Consultant for: Amgen, Bristol-Myers Squibb, Crescendo Biosciences, UCB, AbbVie, Lilly, Pfizer, Roche

Objectives This non-interventional, cross-sectional, descriptive, exploratory analysis aimed to characterise patients (pts) with psoriatic arthritis (PsA) in the 2016 National Health and Wellness Survey (NHWS) and determine the impact of treatment, or no treatment, on pt-reported outcomes. Methods The NHWS was a self-administered, web-based, voluntary, confidential questionnaire. Stratified randomised sampling provided a representative sample of EU adults in France, Germany, Italy, Spain and UK. Respondents completing the arthritis module and reporting PsA diagnosis were stratified by: advanced therapies (tumour necrosis factor inhibitors, interleukin antagonists, phosphodiesterase-4 inhibitors) ± other drugs; other therapies (eg conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, topical medications); or no current treatment. Short Form-36 health survey (SF-36), Work Productivity and Activity Impairment questionnaire and Patient Health Questionnaire-9 (PHQ-9) responses were summarised descriptively. Results NHWS was completed by 80,600 adults; 947 completed the arthritis module and self-reported PsA diagnosis. Of these, 65 (7%) reported receiving advanced therapies, 274 (29%) other therapies and 608 (64%) no current treatment. Age and gender were generally balanced between the groups (mean 51–56 years; 51–64% female). More patients on advanced therapies had a body mass index ≥30 (41%) vs other therapies (34%) and no current treatment (26%). Pts on advanced therapies reported more comorbidities (mean 2.2) vs pts on other therapies (mean 1.8) and pts with no current treatment (mean 1.7). More pts on advanced therapies were current smokers (49%) vs pts on other therapies (30%) and pts with no current treatment (32%). Prior to treatment with advanced or other therapies, 94% and 82% self-reported moderate or severe PsA, falling to 58% and 59%, respectively, after treatment, compared with 36% of pts with no current treatment. SF-36 scores and PHQ-9 scores did not widely vary across groups (Table 1). Regardless of treatment groups, pts reported >20% work loss, >45% overall work impairment and >45% activity impairment (Table 1). Conclusions More than 60% of pts reporting PsA diagnosis reported no current treatment. Regardless of treatment group, pts reported >20% work loss and >45% work impairment. Among treated pts, >50% reported moderate or severe PsA, suggesting a need for overall better management of PsA to reduce the disease impact and improve quality of life. Our results are limited by self-reported PsA diagnosis, which may differ from physician-reported PsA diagnosis, and the survey being conducted in the EU only, which may differ from other parts of the world. Further statistical analyses are needed to determine differences between groups and correlation to other health indicators. Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by A Pedder of CMC and was funded by Pfizer Inc. Disclosure of Interest A. Gottlieb Grant/research support from: Abbott (AbbVie), Amgen, Baxalta, Celgene, Centocor (Janssen), Coronado, Dermira, Eli Lilly, Levia, Merck, Novartis, Pfizer Inc, Xenoport, Consultant for: Abbott (AbbVie), Actelion, Akros, Amgen, Astellas, Baxalta, Beiersdorf, Bristol-Myers Squibb, Canfite, Catabasis, Celgene, Centocor (Janssen), Coronado, CSL Behring Biotherapies for Life, Dermipsor, Eli Lilly, Genentech, GlaxoSmithKline, Incyte, Karyopharm, Meiji Seika Pharma, Mitsubishi Tanabe, Novo Nordisk, Novartis, Pfizer Inc, Takeda, TEVA, UCB, Vertex, Xenoport, J. Gratacos: None declared, A. Dikranian Consultant for: AbbVie, Mallinckrodt, Pfizer Inc, Speakers bureau: AbbVie, Amgen, Celgene, Mallinckrodt, Pfizer Inc, L. Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, B. Emir Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Smith Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Aikman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Chen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background Despite increasing prevalence of gout in the UK (1), a variety of barriers result in suboptimal care (1,2) with only 40% of gout patients receiving urate-lowering therapy (ULT), usually at fixed dose without titration to a serum uric acid (SUA) target (1,2). Nurses successfully manage many chronic diseases in the community, and we have shown that when people with gout are fully informed and involved in management decisions uptake of ULT is high and subsequent adherence under nurse-led care is excellent (3). Objectives To directly compare nurse-led care to general practitioner (GP) care of people with gout in a 2 year randomised controlled trial (NIHR CRN Portfolio No.12943) Methods 517 participants with acute gout in the previous year were identified from 56 local GP practices and randomised to nurse-led or continuing GP care. The nurses were trained about gout and its management according to recommended best practice (EULAR and BSR guidelines) involving full information, addressing illness perceptions, and involving patients in management decisions. Assessments were undertaken at 1 and 2 years. Analysis was intention to treat (last observation carried forward). Results Nurse (n=255) and GP (n=262) groups were well matched at baseline for mean age (62 v 64yrs), sex (90% v 89% men), mean disease duration (11.6 v 12.7yrs), mean gout attack frequency in prior year (4.2 v. 3.8), tophi (13.7% v. 8.8%), mean SUA (443 v. 439 μmol/L), mean eGFR (71.5 v. 70.2) and ULT use (40% v. 39%) (all p>0.05). By 2yrs, 22 (8.6%) and 54 (20.6%) participants had discontinued the nurse and GP groups (p Conclusions Nurse-led care of people with gout in the UK community can result in high uptake and excellent adherence to ULT over a 2yr period, achievement of target SUA in >9/10 cases and consequent improvements in patient-centred outcomes and quality of life. This study reinforces the benefits of “treat-to-target”. Compared to standard GP care this model is likely to be cost effective long-term and merits further consideration. References Doherty M. et al. Ann Rheum Dis 2012;71:1765–70. Kuo C-F. et al. Ann Rheum Dis 2015;74:661–7. Rees F. et al. Ann Rheum Dis 2013:72:826–30. Acknowledgements Arthritis Research UK (Award No.19703) funded this study. Disclosure of Interest M. Doherty Grant/research support from: AstraZeneca, Consultant for: AstraZeneca, Grunenthal, Mallinckrodt and Roche, W. Jenkins: None declared, H. Richardson: None declared, A. Abhishek Grant/research support from: AstraZeneca, D. Ashton: None declared, C. Barclay: None declared, L. Duley: None declared, H. Jones: None declared, M. Santarelli: None declared, A. Sarmanova: None declared, M. Stevenson: None declared, W. Zhang Consultant for: AstraZeneca and Grunenthal

Background Systemic lupus erythematosus (SLE) is a complex yet low prevalence disease. Without a community of lupus specialists to establish consensus and guide best practices, rheumatologists have limited opportunities to develop skills and maintain competence in SLE care. Objectives The objectives of this initiative were to 1) create an independent community of physicians interested in the pathogenesis, diagnosis, and management of patients with SLE and related conditions; 2) share insights and practical guidance for implementing evidence-based care; 3) develop needs-driven continuing medical education (CME) relevant to different levels of clinical expertise; 4) promote collaboration models with publishers to create space for dialogue and community building; and 5) involve patient advocacy groups to steer physician education and incorporate the patient voice into educational activities. Methods The Lupus Academy (http://lupus-academy.org) was established in 2011 as an independent CME initiative led by a Steering Committee of international experts in SLE.[1] Educational activities are designed around unmet clinical needs identified by the Steering Committee, learner survey data, and feedback from patient advocacy groups (including Lupus Europe). Results As of February 2017, the Lupus Academy has grown to a global community of >2,500 committed learners with an interest in SLE. The Steering Committee has guided the development and delivery of 5 2.5-day annual meetings; 4 1-day regional meetings; a meeting toolkit for learner-advocates to host meetings in their home regions; and 3 e-learning courses, with 2 additional courses in production. The 5th Annual Meeting of the Lupus Academy (6–8 May 2016) hosted 101 attendees from Europe, North and South America, and Asia. Learners reported that the learning objectives of the meeting were met (Figure). An assessment of educational effectiveness demonstrated improvements in clinical knowledge and competence (Moore9s Outcomes Levels 3/4) as a result of meeting participation: 67% of learners reported a commitment to implementing changes in clinical practice, 11% reported that the educational content reinforced their current practice, and 20% reported a willingness to modify their current practice with additional training. The most recent regional meeting, the Lupus Academy Middle East Summit Conference (9–10 December 2016), hosted 153 attendees from 13 countries representing diverse specialities: rheumatology (53%), internal medicine (13%), nephrology (11%), clinical immunology (5%), and other (18%). The majority of learners agreed or strongly agreed that the meeting provided an effective platform for the discussion of new ideas in SLE (96%) and challenged the current thinking around lupus care (96%). Conclusions The Lupus Academy serves as an effective model for building a consortium-led, evidence-based educational resource and community of practice for rheumatologists, other physicians with an interest in SLE, and patient advocacy groups. References Ball J, Cervera R, Elzebroek N, Levy RA, Pozniak E. Developing an appropriately supported CME-accredited programme in Europe. J Euro CME. 2013;2:37–44. Acknowledgements Lupus Academy Steering Committee (http://lupus-academy.org/home/lupus-academy-steering-committee/). Disclosure of Interest R. Cervera Consultant for: GSK, UCB, AstraZeneca, Pfizer, Celgene, R. Furie Grant/research support from: AstraZeneca, BiogenIdec, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Mallinckrodt Pharmaceuticals, Medimmune, Pfizer, Sanofi, Takeda, UCB, Consultant for: Anthera, AstraZeneca, Baxalta, BiogenIdec, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Eisai, EMD Merck, Estrela (Janssen), GlaxoSmithKline, Janssen, Mallinckrodt Pharmaceuticals, Medimmune, Novartis, Pfizer, Sanofi, UCB, Z. Amoura Grant/research support from: GSK, Amgen, BMS, Actelion, Roche, Teva, Lilly, Consultant for: GSK, Amgen, BMS, Lilly, A. Jacobson: None declared, E. Pozniak: None declared

Background Fatigue has been identified as one of the most significant symptoms and an outcome of great importance to patients with psoriatic arthritis (PsA), but the association between underlying components of experienced fatigue and the disease has been sparsely investigated. [1] Objectives To describe the degree of fatigue in a PsA population. Secondly, to explore which components of inflammation and non-inflammatory factors contribute to experienced fatigue. Methods The study was designed as a cross-sectional survey including patients registered in DANBIO, the Danish nationwide rheumatologic registry, from December 2013 to June 2014. Principal component analysis was used to identify clustering factors associated with fatigue Results A total of 1,062 PsA patients were included in the study. The median Visual Analog Scale (VAS) fatigue score was 57mm. Patients with moderate to severe fatigue (VAS score ≥57) had higher scores of pain, DAS28, HAQ, patient global assessment, and more tender and swollen joints (p Conclusions Clinical inflammatory disease activity, chronification, as well as pain in the absence of inflammation were all identified as important factors explaining 63% of moderate to severe fatigue in the current PsA population. References Orbai AM, Mease PJ, de WM et al. Report of the GRAPPA-OMERACT Psoriatic Arthritis Working Group from the GRAPPA 2015 Annual Meeting. J Rheumatol 43; 965–9. Acknowledgements This study was supported by the Oak Foundation. Data was extracted from the DANBIO Registry. Disclosure of Interest M. Skougaard: None declared, T. Jorgensen Speakers bureau: Abbvie, Roche, UCB, Novartis, Biogen, S. Rifbjerg-Madsen: None declared, L. Coates Grant/research support from: Abbvie, BMS, Celgene, Jannsen Pharmaceuticals, Lilly, MSD, Novartis, Pfizer, Sun Pharma, UCB, A. Egeberg Grant/research support from: Pfizer, Eli Lilly, Speakers bureau: Pfizer, Eli Lilly, Novartis, Galderma, Janssen Pharmaceuticals, K. Amris: None declared, L. Dreyer: None declared, P. Hojgaard Speakers bureau: Celgene, UCB, J. Guldberg-Moller Paid instructor for: Abbvie, J. Merola Grant/research support from: Biogen IDEC, Amgen, Pfizer, Boehringer Ingelheim, Consultant for: Biogen IDEC, Eli Lilly, Novartis, Momenta, UCB, Kiniksa, AbbVie, Amgen, Pfizer, Janssen Pharmaceuticals, Momenta, Mallinckrodt, Speakers bureau: AbbVie, Eli Lilly, P. Frederiksen: None declared, H. Gudbergsen Speakers bureau: MSD, Pfizer, L. E. Kristensen Speakers bureau: Pfizer, AbbVie, Amgen, UCB, Celgene, BMS, MSD, Novartis, Eli Lilly, Janssen Pharmaceuticals.

Background Selection of the correct target to guide treatment is crucial for effective disease management in patients with psoriatic arthritis (PsA). Objectives To evaluate the prognostic value of several low disease activity (LDA) measurements in patients with PsA and psoriasis to assist physicians choose a valid target that facilitates assessment in clinical practice. Methods This was a post-hoc analysis from the PRESTA 1 clinical study. LDA targets analyzed were: Disease Activity in PsA (DAPSA) LDA ≤14 (tender joint count [TJC], swollen joint count [SJC], patient global visual analog scale [Pt VAS], pain VAS, C-reactive protein [CRP]; clinical (c)DAPSA LDA ≤13 (DAPSA without CRP); and minimal disease activity (MDA) measurement defined as 5/7 cut-offs (TJC ≤1, SJC ≤1, psoriasis activity and severity index [PASI] ≤1, Pt pain ≤15mm, Pt VAS ≤20mm, health assessment questionnaire ≤0.5, tender entheseal points ≤1). Additional MDA measurements were investigated where 5/7 cut-offs were met but some were mandated: MDA_joint with both TJC and SJC cut-offs mandated, MDA_skin where PASI cut-off was mandated, MDA_joint+skin where the TJC, SJC, and skin cut-offs were mandated. Results At Week 24, the proportion of patients achieving LDA were 47%, 20%, 38%, 14% in MDA 5/7, MDA_skin, MDA_joint, MDA_joint+skin, respectively, vs ∼71% in DAPSA and cDAPSA LDA. The highest proportion of discordance was observed between MDA_skin or MDA_joint+skin with DAPSA LDA or cDAPSA LDA (Figure). The majority of patients had no residual arthritis although levels were highest in the DAPSA measurements (Table). However, notable residual levels of psoriasis were observed in measurements that did not require skin disease control (Table 1). MDA_joint+skin had the lowest levels of residual disease across all cut-offs (Table 1). At Week 12, a significant difference (P Conclusions DAPSA and cDAPSA LDA provided the least stringent cut-offs with the highest percentages of patients with residual disease. Whilst choosing the optimal target for treatment requires more debate, it is clear from these data that levels of residual psoriasis are high in those measurements that do not require skin control. If this is not included in a treatment target for PsA, notable levels of psoriasis can be missed. References Sterry W, et al. BMJ 2010;340:c1471. Disclosure of Interest L. Coates Grant/research support from: Abbvie, Janssen, Consultant for: Abbvie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, A. Gottlieb Grant/research support from: Centocor (Janssen), Amgen, Abbvie, Novartis, Celgene, Pfizer, Lilly, Levia, Merck, Xenoport, Dermira, Baxalta, Consultant for: Amgen, Astellas, Akros, Centocor (Janssen), Celgene, Bristol Myers Squibb, Beiersdorf, Abbvie, TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor, Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Karyopharm, CSL Behring Biotherapies for Life, Glaxo Smith Kline, Xenoport, Catabasis, Meiji Seika Pharma, Takeda, Mitsubishi,Tanabe Pharma Development America, Genentech, Baxalta, Kineta One, KPI Therapeutics, Crescendo Bioscience, Aclaris, Amicus, Reddy Labs, Speakers bureau: Abbvie, J. Merola Consultant for: Biogen IDEC, AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Janssen, UCB, Kiniksa, Momenta and Mallinckrodt, L. Aikman Shareholder of: Pfizer, Employee of: Pfizer, A. Szumski Employee of: InVentiv Health, A. Chhabra Shareholder of: Pfizer, Employee of: Pfizer

Background Tofacitinib is an oral Janus kinase inhibitor under investigation for treatment of psoriatic arthritis (PsA). Objectives To assess the efficacy and safety of tofacitinib vs placebo (PBO) in patients (pts) with active PsA. Methods Eligible pts in this randomised, PBO- and active-controlled, 12-month Phase 3 trial had ≥6-months9 PsA diagnosis, fulfilled CASPAR criteria, had active arthritis (≥3 tender/painful and ≥3 swollen joints) and active plaque psoriasis at screening, inadequate response to ≥1 csDMARD, and were tumour necrosis factor-inhibitor (TNFi)-naive. 422 pts were randomised 2:2:2:1:1 to tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg subcutaneous injection every 2 weeks, or PBO (advancing to tofacitinib 5 or 10 mg BID at Month [M]3). Stable treatment with 1 csDMARD was required. Primary endpoints comparing tofacitinib vs PBO were ACR20 response rate and change from baseline in Health Assessment Questionnaire Disability Index (ΔHAQ-DI) at M3. Secondary endpoints included: ACR20 response rates and ΔHAQ-DI through M12; pts achieving ACR50, ACR70, ≥75% improvement of PASI and PsARC at all time points; and changes from baseline in LEI, Dactylitis Severity Score and SPARCC Enthesitis Index. Radiographic progression was assessed by van der Heijde-modified Total Sharp Score (mTSS). Results 96.9% of pts were white and 53.3% were female; mean age was 47.9 years. 96.2% and 88.4% of pts completed M3 and M12, respectively. At M3, tofacitinib 5 and 10 mg BID significantly improved ACR20 response rates (50.5% [p≤0.05] and 60.6% [p 91% of pts were radiographic non-progressors at M12 (defined as an increase from baseline in mTSS ≤0.5). M12 safety findings were similar between groups (Fig 1E). The most common adverse events were upper respiratory tract infection (7.5–10.6%), nasopharyngitis (7.5–11.5%) and headache (3.8–10.6%). Conclusions In TNFi-naive pts with active PsA, tofacitinib was superior to PBO in ACR20 response rates and ΔHAQ-DI at M3, with superiority vs PBO as early as Week 2 for ACR20, which was maintained to M12. No new safety risks were identified vs previous studies in other indications. Acknowledgements Previously presented at ACR 2016, to be presented at AAD 2017 and reproduced with permissions. This study was sponsored by Pfizer Inc. Editorial support was provided by AG McCluskey of CMC and was funded by Pfizer Inc. Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sun, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, CORRONA, Dermira, Janssen, Eli Lilly, Merck, Novartis, Pfizer Inc, Sun, UCB, Zynerba, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Novartis, Pfizer Inc, UCB, S. Hall Consultant for: AbbVie, Celgene, Eli Lilly, Janssen, Pfizer Inc, Roche, O. FitzGerald Grant/research support from: AbbVie, Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Speakers bureau: Celgene, Janssen, Novartis, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer Inc, Roche, Sanofi-Aventis, UCB, Employee of: Imaging Rheumatology BV, J. Merola Grant/research support from: Biogen Idec, Consultant for: AbbVie, Amgen, Biogen Idec, Eli Lilly, Janssen, Momenta, Mallinckrodt, Novartis, Pfizer Inc, Speakers bureau: AbbVie, Eli Lilly, F. Avila-Zapata: None declared, D. Cieślak: None declared, D. Graham Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background Type I interferons (IFN-I) are central to the pathogenesis of systemic lupus erythematosus (SLE). BDCA2 is a plasmacytoid dendritic cell (pDC)-specific receptor that, upon engagement, inhibits the production of IFN-I and other inflammatory mediators. Targeting BDCA2, therefore, represents an attractive therapeutic strategy for inhibiting pDC-driven inflammation that is such a key feature of SLE pathogenesis. BIIB059, an investigational anti-BDCA2 humanized monoclonal antibody, has been shown to engage BDCA2, and this interaction leads to BDCA2 internalization and the consequent in vitro inhibition of TLR-induced IFN-I production by pDCs (Pellerin 2015). Objectives This first-in-patient study aimed to assess safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects and clinical activity of BIIB059 in adult SLE patients with active cutaneous lupus (CLE) following administration of a single BIIB059 dose. Methods A Phase 1b randomized, double-blinded, placebo controlled, multicenter clinical trial was conducted in 12 adult SLE subjects (meeting 1997 ACR criteria) with active cutaneous manifestations (including acute, sub-acute and/or chronic cutaneous forms of cutaneous lupus erythematosus (CLE)). Subjects received a single IV administration of either BIIB059 20mg/kg (n=8) or placebo (n=4). A panel of IFN-responsive genes (IRG) was assessed from whole blood by qPCR at baseline and several post-dose time points. Skin biopsies from active lesions were obtained and evaluated at baseline and week 4 for IFN-regulated proteins, including MxA and IFITM3 using quantitative immunohistochemistry. CLE disease activity was assessed using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), and safety data, including adverse events (AEs) and laboratory tests, were also collected. Results Most SLE subjects had high IRG signatures in the blood. Skin biopsies demonstrated features of inflammation consistent with active CLE, including elevated expression of MxA and other IFN-regulated proteins. A single dose of BIIB059 decreased the expression of IRG in blood and MxA and IFITM3 proteins in the skin in most patients. CD45+ cells were reduced in skin biopsies of BIIB059-treated patients. The reduction in inflammatory cells as well as MxA and IFITM3 expression at week 4 correlated with improvement in CLASI activity score at multiple timepoints post-dose. BIIB059 was generally well tolerated with no discontinuations due to AEs. The incidence of AEs was similar between BIIB059- and placebo-treated SLE subjects, and most AEs were mild or moderate in severity. Conclusions A single dose of BIIB059 resulted in inhibition of the IRG in peripheral blood and MxA and IFITM3 expression in lesional skin of SLE subjects, consistent with BIIB0599s proposed mechanism of action. The clinical and biomarker data together confirm the role of human pDCs in the pathogenesis of SLE, and support further development of BIB059 in SLE. Disclosure of Interest R. Furie Consultant for: Biogen, V. Werth Grant/research support from: Biogen, Consultant for: Biogen, J. Merola Grant/research support from: Biogen, Consultant for: Biogen, AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Janssen, Mallinckrodt, Momenta, Speakers bureau: AbbVie, Eli Lilly, T. Reynolds Shareholder of: Biogen, Employee of: Biogen, L. Stevenson Shareholder of: Biogen, Employee of: Biogen, W. Wang Shareholder of: Biogen, Employee of: Biogen, K. Smirnakis Shareholder of: Biogen, Employee of: Biogen, C. Barbey Shareholder of: Biogen, Employee of: Biogen, C. Musselli Shareholder of: Biogen, Employee of: Biogen, B. Werneburg Shareholder of: Biogen, Employee of: Biogen, D. Rabah Shareholder of: Biogen, Employee of: Biogen, N. Franchimont Shareholder of: Biogen, Employee of: Biogen

Background Recent studies have indicated that being overweight or obese could reduce the effect of anti-TNF treatment in patients (pts) with RA. 1,2 Other data show that certain biologic (b)DMARDs, such as abatacept, work independently of BMI. 3,4 Additional data on the role of BMI on treatment outcomes in clinical practice settings is required to inform clinical practice. Objectives To evaluate the impact of BMI on outcomes of disease activity in pts with RA treated with TNF and non-TNF agents (conventional or other bDMARDs). Methods Pts enrolled in a tertiary care centre RA registry, established in 2003, were analysed. The registry mostly comprises pts with established RA who were evaluated semi-annually for multiple clinical patient-reported outcomes and resource utilization parameters, and annually for composite disease activity measures such as DAS28 (CRP), CDAI and SDAI. The current analysis is based on pts enrolled in the RA registry with BMI values at time of enrolment. Pts were classified into groups based on BMI: normal (BMI 2 ), overweight (BMI ≥25 to 2 ) and obese (BMI ≥30 kg/m 2 ). Outcomes evaluated included change from baseline in DAS28 (CRP), CDAI, SDAI and joint counts at 12 months from treatment exposure. Treatments were categorized into TNF and non-TNF, which included conventional DMARDs and other non-TNF biologics. Multivariate linear regression analyses were used to evaluate impact of BMI on treatment outcomes controlling for baseline covariates of age, sex, disease duration, co-morbidities, baseline disease activity and serostatus. Separate models were run for the TNF and non-TNF groups. Results A total of 997 (78%) pts in the registry had baseline BMI values and were included in the analysis. Around 37% (n=371) had TNF exposure and were included in the TNF cohort; the remainder (63%; n=626) were included in the non-TNF cohort. Proportions of pts in the normal, overweight and obese groups for the TNF cohort were 45.5% (n=169), 27.5% (n=102) and 27.0% (n=100), respectively. For the non-TNF cohort, these were 41.7% (n=261), 33.1% (n=207) and 25.2% (n=158), respectively. In both cohorts, pts with normal BMIs were younger vs the overweight and obese BMI groups. However, obese BMI pts had higher disease activity measures at baseline (mean [SD] CDAI: 22.8 [17.8] for TNF and 24.9 [17.3] for non-TNF) vs the normal BMI pts (17.5 [15.9] for TNF and 19.9 [16.7] for non-TNF) and overweight BMI pts (20.9 [16.5] for TNF and 20.5 [15.0] for non-TNF). Adjusted mean change from baseline in disease activity in the TNF cohort was significantly reduced across all disease activity measures for the normal BMI group (p Conclusions Independent of BMI, non-anti-TNF therapy demonstrated similar outcomes in pts with RA. However, obese and overweight pts with RA (vs normal weight) had less improvement in disease activity (as measured by DAS28 [CRP]) with anti-TNF therapy. References Gremese E, et al. Arthritis Care Res 2013;65:94–100. Klaasen R, et al. Arthritis Rheum 2011;63:359–64. Gardette A, et al. Ann Rheum Dis 2015;74:1041. Disclosure of Interest E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Z. Guo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, C. Iannaccone: None declared, M. Frits: None declared, M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Biosciences, UCB, DxTerity, Consultant for: Amgen, Bristol-Myers Squibb, Crescendo Biosciences, UCB, AbbVie, Lilly, Pfizer, Roche, N. Shadick Grant/research support from: Bristol-Myers Squibb, UCB, Mallinckrodt, Amgen, Brescendo Biosciences, Consultant for: Bristol-Myers Squibb