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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 and Aim: T2D is an independent risk factor for the development of nonalcoholic steatohepatitis (NASH). Amongst NASH patients, those with elevated disease activity (NAS≥4) and fibrosis (F≥2) upon scoring of a liver biopsy are at higher risk of progressing to negative clinical outcomes. There is a lack of diagnostic tools to identify these “at-risk𠇍 NASH patients that need clinical intervention. Here we compare the ability of NIS4, a novel blood test, to other available tests for detection of “at-risk” NASH in a T2D population. Methods: The blood and liver biopsy samples from 714 patients (446 non-T2D + 268 T2D) with metabolic risk factors for NASH were used. Disease activity (NAS) and fibrosis stage (F) were evaluated by a single expert pathologist. “At-risk” NASH was defined as NASH with NAS≥4 and F≥2. The diagnostic performance of NIS4 to identify patients with “at-risk” NASH in T2D subpopulation was assessed through ROC analysis and compared versus existing tests and statistical comparisons were done by DeLong testing. Results: In the total cohort (T2D prevalence = 38%), AUROC of NIS4 was 0.83 [95% CI: 0.80 - 0.86] for identifying “at-risk” NASH. The prevalence of “at-risk” NASH was higher in T2D (61%) vs. non-T2D (45%). AUROC was comparable in T2D and non-T2D: 0.80 [0.75 - 0.85] vs. 0.83 [0.80 - 0.87]. In T2D, a head to head comparison (AUROC; 95% CI) showed that NIS4 [0.80; 0.75-0.85] significantly outperformed all other tests for the identification of “at-risk” NASH: APRI [0.74; 0.68-0.80], FIB4 [0.70; 0.64-0.77], ELF [0.70; 0.64-0.77], FibroTest [0.68; 0.61-0.74], and NFS [0.60; 0.52-0.67]. Conclusion: Amongst T2D patients with suspected NASH, the prevalence of “at-risk” NASH is high. This highlights the need for active surveillance amongst T2D patients. For that purpose, NIS4 outperforms other tests and is a promising non-invasive tool to identify and potentially track T2D patients who need clinical intervention to manage their disease. Disclosure B. Staels: None. V. Ratziu: Other Relationship; Self; Gilead Sciences, Inc. S. Francque: Consultant; Self; GENFIT. S.A. Harrison: Advisory Panel; Self; Gilead Sciences, Inc. P. Bedossa: Consultant; Self; GENFIT. A. Roudot: Employee; Self; GENFIT. Z. Majd: Employee; Self; GENFIT. J. Brozek: Employee; Self; GENFIT. F. Ben-Sudrik: Employee; Self; GENFIT. P. Birman: Employee; Self; GENFIT. D.W. Hum: Employee; Self; GENFIT. S. Hosmane: Employee; Self; GENFIT. P. Chaumat: Employee; Self; GENFIT. R. Hanf: Employee; Self; GENFIT. B. Cariou: Board Member; Self; Novo Nordisk A/S, Regeneron Pharmaceuticals. Consultant; Self; GENFIT, Sanofi-Aventis. Research Support; Self; Amgen Inc., Pfizer Inc. Speaker’s Bureau; Self; Abbott, Akcea Therapeutics, Merck Sharp & Dohme Corp. A. Sanyal: Consultant; Self; Ardelyx, Boehringer Ingelheim Pharmaceuticals, Inc., Exhalenz, Gilead Sciences, Inc., Hemoshear, Intercept Pharmaceuticals, Inc., Lilly, Mallinckrodt Pharmaceuticals, Nimbus Therapeutics, Nitto Denko, Novartis Pharmaceuticals Corporation, Pfizer Inc. Employee; Self; Sanyal Bio. Research Support; Self; Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Echosens, Galectin Therapeutics Inc., Immuron Ltd, Merck & Co., Inc., Salix Pharmaceuticals, Sequanna. Stock/Shareholder; Self; Akarna Therapeutics, GENFIT, Natural Shield, NewCo LLC, Tiziana. Other Relationship; Self; Elsevier, UpToDate.

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: Diabetes is a risk factor for advanced fibrosis due to NASH, but the effect of diabetes on disease progression is not well-characterized. Here, we describe clinical outcomes for patients with and without diabetes in two negative, randomized, placebo-controlled trials of simtuzumab. Methods: 217 patients with bridging fibrosis (F3) and 258 subjects with compensated cirrhosis (F4) were enrolled. Liver biopsies were reviewed by a central pathologist at screening and weeks 48 and 96. Patients were stratified based on the presence or absence of diabetes. Adjudicated clinical outcomes included: esophageal varices, variceal bleeding, ascites, hepatic encephalopathy, ≥2 point increase in Child-Pugh-Turcotte score, MELD >15, or death. Results: 145 (67%) of patients with F3 and 179 (69%) of patients with F4 had diabetes at baseline. Median age was 56 years. By week 96, 25% (31/129) of F3 patients with diabetes had progressed to cirrhosis, compared to 18% (11/67) of patients without diabetes [p=0.27]. Cirrhotic (F4) patients with diabetes had a higher rate of clinical events (Figure). Conclusion: Diabetes is common in patients with advanced fibrosis due to NASH and associated with numerically higher rates of progression. Larger studies are needed to confirm these findings. Patients with diabetes have a high unmet need for therapies that target advanced fibrosis due to NASH. Disclosure A.J. Sanyal: Consultant; Self; Ardelyx, Boehringer Ingelheim Pharmaceuticals, Inc., Exhalenz, Gilead Sciences, Inc., Hemoshear, Intercept Pharmaceuticals, Inc., Lilly, Mallinckrodt Pharmaceuticals, Nimbus Therapeutics, Nitto Denko, Novartis Pharmaceuticals Corporation, Pfizer Inc. Employee; Self; Sanyal Bio. Research Support; Self; Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Echosens, Galectin Therapeutics Inc., Immuron Ltd, Merck & Co., Inc., Salix Pharmaceuticals, Sequanna. Stock/Shareholder; Self; Akarna Therapeutics, GENFIT, Natural Shield, NewCo LLC, Tiziana. Other Relationship; Self; Elsevier, UpToDate. M.F. Abdelmalek: Advisory Panel; Self; Allergan, Bristol-Myers Squibb Company, Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Prometic Life Sciences Inc. Consultant; Self; TaiwanJ Pharmaceuticals Co., Ltd. Research Support; Self; Akcea Therapeutics, Allergan, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Galectin Therapeutics Inc., GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Prometheus, Shire, TaiwanJ Pharmaceuticals Co., Ltd. Speaker's Bureau; Self; Alexion Pharmaceuticals, Inc. S. Caldwell: Research Support; Self; Conatus Pharmaceuticals Inc., Galmed Pharmaceuticals Ltd., GENFIT, Gilead Sciences, Inc., Halyard, Mallinckrodt Pharmaceuticals, TARGET PharmaSolutions, Vital Therapy, Zydus Pharmaceuticals, Inc. Other Relationship; Self; Dova. M.L. Shiffman: Advisory Panel; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. Research Support; Self; Allergan, Conatus, Enanta Pharmaceuticals, Inc., Exhalenz, GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Novartis AG, Shire. Speaker's Bureau; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. R. Ghalib: None. E. Lawitz: Research Support; Self; birdrock bio, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Durect Corporation, Enanta Pharmaceuticals, Inc., Galmed Pharmaceuticals Ltd., GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., madrigal, Novartis AG, octeta, Zydus Cadila. D. Jiang: Employee; Self; Gilead Sciences, Inc. R.E. Aguilar Schall: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. B.J. McColgan: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. R. Myers: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. S. Djedjos: Employee; Self; Gilead Sciences, Inc. A. Muir: Advisory Panel; Self; AbbVie Inc., Gilead Sciences, Inc. Research Support; Self; AbbVie Inc., Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., NGM Biopharmaceuticals. V. Ratziu: Other Relationship; Self; Gilead Sciences, Inc. N. Afdhal: Advisory Panel; Self; Gilead Sciences, Inc., Ligand Pharmaceuticals, Inc. Consultant; Self; Echosens. Employee; Self; Spring bank Pharmaceuticals. Z. Goodman: None. J. Bosch: Advisory Panel; Self; Actelion Pharmaceuticals US, Inc., Conatus Pharmaceuticals Inc., Exhalenz. S.A. Harrison: Advisory Panel; Self; Gilead Sciences, Inc. Funding Gilead Sciences, Inc.

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

The US government has joined two whistleblower lawsuits as a co-plaintiff against the drug firm Mallinckrodt, accusing the company of paying kickbacks to doctors to increase prescriptions of a drug whose price has risen more than 97 000%, from $40 a vial in 2000 to nearly $39 000 (£30 000; €35 000) today. The lawsuits allege that cash payments, gifts, and junkets drove a small number of doctors to make HP Acthar Gel (repository corticotropin injection), a blockbuster drug with annual sales totalling more than $1bn, much of it coming from Medicare. Approved in 1952 to treat spasms in infants, Acthar has come to be used in adult conditions as varied as nephrotic syndrome, psoriatic or rheumatoid arthritis, sarcoidosis, optic neuritis, ankylosing spondylitis and, most lucratively, multiple sclerosis. But in addition to healthy profits the drug …

Background 177Lu-DOTATATE peptide receptor radionuclide therapy is administered to patients on an inpatient and outpatient basis for the treatment of well-differentiated, metastatic neuroendocrine tumours. Following administration, these patients present an external radiation hazard due to the gamma emissions of lutetium-177. The purpose of this study was to determine precautions to be observed by 177Lu-DOTATATE patients to restrict the dose received by patients’ family members to less than 5 mSv in 5 years and members of the public to less than 1 mSv per year in line with the current UK legislation. Retrospective data from therapeutic administrations of 177Lu-DOTATATE (Mallinckrodt Pharmaceuticals) and Lutathera® (Advanced Accelerator Applications) were analysed to measure activity retention at discharge. Patient dose rate measurements were assumed to follow the same activity decay curve as that derived from a least squares fit of geometric mean counts in planar whole-body scans performed at four time points post-administration. Combining this with social contact times, the cumulative dose received through contact with the patient was estimated and an iterative process used to determine the length of contact restrictions to ensure the relevant dose constraints are not exceeded. Results On average, 36% of the administered activity was retained at the time of discharge for inpatients receiving 177Lu-DOTATATE (Mallinckrodt). Retentions of 24% and 38% were measured for Lutathera® inpatients and outpatients respectively. Inpatients should restrict day contact and sleep separately from their partner for 15 days and remain off work for 5 days post-therapy. Contact with children for whom the patient is the main carer should be restricted for 16, 13 and 9 days for children below 2, 2–5 and 5–11 years respectively. One additional day is added to outpatient restriction periods, except for children aged 2–5 years which remains 13 days. No private transport restrictions are required. Patients should limit travel by public transport to 1 h on the day of discharge. Conclusion Restrictions are necessary to limit radiation dose to members of patients’ household and the public. Proposed precautions for inpatient and outpatient 177Lu-DOTATATE therapy protocols restrict the dose received to less than the limit imposed by the UK legislation.

Background Lupus Nephritis (LN) usually presents within five years of SLE diagnosis. Male gender, Hispanic and African American race, and childhood-onset SLE portend greater risk of early nephritis. However, patients with late-occurring nephritis are poorly characterized. Since proliferative nephritis is a more aggressive class of nephritis than membranous and mesangial, we hypothesized that female gender, Caucasian race, adult-onset SLE, and membranous pathology would be associated with a later onset of nephritis. Methods A single large urban medical center was the source for retrospective record review of patients who underwent kidney biopsy between 1999 and 2015. Patients with biopsy-proven LN were evaluated to determine whether gender, race, age at SLE diagnosis, age at first biopsy, or histopathologic classification were associated with time between SLE diagnosis and first renal biopsy. Results 630 patients were screened. After elimination of duplicates, those without initial biopsy, biopsy findings other than LN, and unknown date of SLE diagnosis, 293 subjects had adequate data available for analysis. Those with late onset SLE, diagnosis after age 50, were excluded from further analysis due to known differences in this subgroup. The remaining 278 patients had characteristics shown in table 1. Twenty-nine percent of patients in this cohort developed nephritis more than 5 years after initial SLE diagnosis. Multivariable linear regression identified greater age at first biopsy and race as the strongest predictors of time between SLE diagnosis and first renal biopsy. Hispanic patients were more likely to present with LN earlier in their course and Asian patients were more likely to present later, with African American and Caucasian groups between them. The model accounts for 27% of the variability in the time elapsed between diagnosis and biopsy. Histopathologic class did not make a significant contribution, and proliferative nephritis was noted in similar numbers of patients who developed LN after 5 years and those in the early presenting group. Conclusions Surprisingly, more than a quarter of known LN patients at this large US center present after 5 years of SLE, higher than expected based on low numbers of late onset nephritis in other cohorts. This appears to be more common in Caucasian and Asian subgroups. Older patients are more likely to develop nephritis later, but aggressive histopathology is not less likely in later presentations. The data underscore the importance of remaining vigilant about nephritis risk in patients of diverse demographics five years and more after diagnosis with SLE. Funding Source(s): Mallinckrodt Research Fellowship, NIH:T32DK007257,UL1TR001105,U54GM104938,P30AR053483,U01AI101934,U19AI082714

This retrospective study examined the effect of adrenocorticotropic hormone therapy on remission of recurrent focal segmental glomerulosclerosis (FSGS) in patients with history of kidney transplant (KT) treated at 2 transplant centers. Patients with biopsy-confirmed FSGS following KT who received Acthar Gel (Mallinckrodt ARD, Bedminster, New Jersey, United States) treatment for ≥1 month were eligible. A total of 14 patients with idiopathic FSGS were included. Acthar Gel treatment resulted in complete remission of FSGS in 3 patients and partial remission in 2 patients for a total treatment response rate of 36% (5/14) of patients. Among patients showing complete or partial remission, Acthar Gel treatment duration ranged from 6 months to 2 years and 60% (3/5 patients) had serum creatinine ≤ 2 mg/dL at the start of Acthar Gel treatment. Patient outcomes suggest Acthar Gel may be an effective and tolerable treatment for recurrent FSGS in patients with history of KT. Early initiation of Acthar Gel treatment and therapy duration of at least 6 months may be needed for optimal response to Acthar Gel in patients with history of KT and recurrent FSGS.

Background:Some patients with SSc-ILD develop dyspnoea secondary to parenchymal lung disease, while others do not report dyspnoea even when their lung function is impaired. It is unclear whether the presence of dyspnoea is associated with a worse course of SSc-ILD or with response to therapy.Objectives:To investigate the rate of decline in FVC in patients with SSc-ILD in the SENSCIS trial in subgroups by patient-reported dyspnoea at baseline.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom within ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT and FVC ≥40% predicted. Patients were randomised to receive nintedanib or placebo until the last patient reached week 52. In post-hoc analyses, we analysed the rate of decline in FVC (mL/year) over 52 weeks in patients with and without dyspnoea at baseline based on the question about dyspnoea in the St. George’s Respiratory Questionnaire (SGRQ). Patients who reported having shortness of breath “most days a week”, “several days a week” or “a few days a month” (rather than “only with chest infection” or “not at all”) over the last month were considered to have dyspnoea at baseline. A random slope and intercept model was used to assess the rate of decline in FVC (mL/year) and an interaction test was applied to assess potential heterogeneity in the treatment effect of nintedanib between the subgroups.Results:Of 576 patients, 69.8% had dyspnoea at baseline. At baseline, in patients with and without dyspnoea, respectively, mean (SD) extent of fibrotic ILD on HRCT was 37.7 (21.7)% and 31.6 (19.4)%; mean (SD) FVC was 71.0 (16.3) and 76.5 (16.8) % predicted; 50.7% and 44.8% were taking mycophenolate; 53.5% and 41.9% were taking corticosteroids. In the placebo group, the rate of decline in FVC (mL/year) was similar in patients with and without dyspnoea at baseline (Figure). The effect of nintedanib versus placebo on reducing the rate of decline in FVC (mL/year) was numerically more pronounced in patients without dyspnoea (difference: 79.8 [95% CI: 9.8, 149.7]) than with dyspnoea (difference: 25.7 [-19.9, 71.3]), but the exploratory interaction p-value did not indicate heterogeneity in the treatment effect between subgroups (p=0.20).Conclusion:In the SENSCIS trial, patients with SSc-ILD who had dyspnoea at baseline had a numerically greater extent of fibrotic ILD on HRCT and numerically lower FVC % predicted at baseline. The rate of decline in FVC in the placebo group was similar in patients with and without dyspnoea. Nintedanib had a numerically greater treatment effect in patients without dyspnoea. These data suggest that the presence of dyspnoea should not be used as a criterion for starting nintedanib in patients with SSc-ILD.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by Fleishman Hillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus and Forbius, Michael Kreuter Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim and Roche, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, Merck Sharp & Dohme and Roche, Consultant of: Actelion, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Marlies Wijsenbeek Speakers bureau: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Consultant of: Boehringer Ingelheim (fees paid to institution), Bristol-Myers Squibb (fees paid to institution), Galapagos NV (fees paid to institution), Hoffmann-La Roche (fees paid to institution), NeRRe Therapeutics (fees paid to institution), OncoArendi Therapeutics (fees paid to institution), Respivant Sciences (fees paid to institution) and Savara (fees paid to institution), Grant/research support from: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Vanessa Smith Speakers bureau: Boehringer Ingelheim and Janssen-Cilag NV, Consultant of: Boehringer Ingelheim, Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim, Janssen-Cilag NV and Research Foundation - Flanders (FWO), Dinesh Khanna Shareholder of: Eicos Sciences, Inc. (less than 5%), Consultant of: Acceleron Pharma, Actelion, AbbVie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead Sciences, Galapagos NV, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Sanofi-Aventis and United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health and Pfizer, Employee of: Chief Medical Officer- CiviBioPharma/Eicos Sciences, Inc., Christopher Denton Speakers bureau: Boehringer Ingelheim, Corbus, Janssen, and Mallinckrodt Pharmaceuticals, Consultant of: Acceleron Pharma, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mallinckrodt Pharmaceuticals, Roche, Sanofi and UCB, Grant/research support from: Arxx Therapeutics, GlaxoSmithKline and Servier, Wim Wuyts: None declared, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Steven Sambevski Employee of: Currently an employee of Boehringer Ingelheim, Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals

Background:ABBV-3373 is a novel antibody drug conjugate composed of adalimumab (ADA) linked to a proprietary and highly potent glucocorticoid receptor modulator (the anti-inflammatory payload) currently evaluated for the treatment of rheumatoid arthritis (RA).Objectives:To assess the efficacy and safety of ABBV-3373 vs ADA in RA patients (pts).Methods:This was a 24-week (wk) randomized, double-blind, double-dummy, active-controlled Phase 2a study of intravenously (IV)-administered ABBV-3373 100 mg (for 12 wks followed by placebo [PBO] for 12 wks) vs subcutaneous injections of ADA 80 mg every other wk (for 24 wks) in pts on background methotrexate. The primary endpoint was the change from baseline (BL) in DAS28(CRP) at Wk 12. Pre-planned statistical methods incorporating pre-specified historical ADA data both alone (pre-specified success criterion, 2-sided P ≤0.1) and supplemented with in-trial ADA data (pre-specified success criterion, probability >95%) were used to achieve adequate statistical power with a reduced trial size. Assay sensitivity was evaluated through construction of a synthetic PBO arm by propensity score matching, using individual pt-level PBO data from 3 recent sponsor-run trials of similar populations and trial settings. Secondary endpoints at Wk 12 included 1) mean change from BL in CDAI, SDAI, DAS28(ESR), HAQ-DI; 2) proportion of pts achieving DAS28(CRP)≤3.2, ACR20/50/70 responses, HAQ-DI≤-0.22. Continuous and categorical efficacy variables were analyzed using mixed effect model repeated measurements and Cochran-Mantel-Haenszel test, respectively; non-responder imputation was applied to missing categorical data. Treatment-emergent adverse events were summarized through Wk 12.Results:A total of 48 pts were randomized and treated (ABBV-3373: 31; ADA: 17); 46 pts (96%) completed 12 wks of study treatment. BL demographics and disease characteristics were indicative of established RA and similar among the 2 treatment arms and the synthetic PBO arm. ABBV-3373 demonstrated significant improvement in mean DAS28(CRP) at Wk 12 vs the pre-specified historical ADA (-2.65 vs -2.13; P=0.022) and numerically greater improvement vs the combined in-trial and historical ADA arm (-2.65 vs -2.29; probability 90%; Figure). Comparable improvements in disease activity and targets were observed for ABBV-3373 and in-trial ADA. Assay sensitivity was supported by the fact that both ABBV-3373 and ADA arms were superior to synthetic PBO (PTable 1.Treatment Emergent Adverse Events up to Week 12Event, n (%)ADA(N = 17)ABBV-3373(N = 31)Adverse event (AE)12 (70.6)11 (35.5)AE with reasonable possibility of being drug related$3 (17.6)2 (6.5)Severe AE01 (3.2)Serious AE04 (12.9) #AE leading to Discontinuation of Study Drug1 (5.9)1 (3.2)Serious infections02 (6.5)Opportunistic infection excluding Tuberculosis00Allergic Reactions Including Hypersensitivity, Angioedema, and Anaphylaxis2 (11.8) &1 (3.2) ^Systemic glucocorticoid events00All deaths00$As assessed by investigator. #Serious AEs: 1 non-cardiac chest pain, 1 pneumonia, 1 upper respiratory tract disease and 1 anaphylactic shock. &1 Type I hypersensitivity, 1 Pruritus ^1 Anaphylactic shockConclusion:These data demonstrate the clinical efficacy of ABBV-3373 and its potential to provide improved outcomes for RA pts compared to ADA. The safety profile of ABBV-3373 was generally similar to ADA.Acknowledgements:AbbVie and the authors we thank the patients, trial sites, and investigators who participated in this clinical trial. AbbVie, Inc was the trial sponsor, contributed to trial design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. The authors thank Yang Yang of AbbVie Inc for supporting the statistical analysis and data reporting. Medical writing support was provided by Ramona Vladea, PhD of AbbVie, Inc.Disclosure of Interests:Frank Buttgereit Consultant of: AstraZeneca, AbbVie, Grünenthal, Horizon Pharma, Pfizer, and Roche, Grant/research support from: AbbVie, Horizon Pharma, Pfizer, and Roche, Jacob Aelion Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Eli Lilly, Galapagos/Gilead, Genentech, GlaxoSmithKline, Horizon, Janssen, Mallinckrodt, Nektar, Nichi-Iko, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis, Selecta, UCB, Bernadette Rojkovich: None declared, Anna Zubrzycka-Sienkiewicz Consultant of: Astellas and Roche, Grant/research support from: AbbVie, Astellas, Galapagos NV, Gilead Sciences, Janssen, Lilly, Mabion, Pfizer, Roche, and UCB SA, Timothy Radstake Shareholder of: AbbVie, Employee of: AbbVie, Su Chen Shareholder of: AbbVie, Employee of: AbbVie, Dilek Arikan Shareholder of: AbbVie, Employee of: AbbVie, Hartmut Kupper Shareholder of: AbbVie, Employee of: AbbVie, Howard Amital Consultant of: Abbvie, Janssen, Novartis, Roche, Perrigo, Pfizer, Neopharm, Elly Lilly, Gilead, Sanofi, Teva and Rafa, Grant/research support from: Yansen, Pfizer

Background:Dermatomyositis (DM) is a rare chronic systemic autoimmune disease with characteristic skin rash and progressive proximal muscle weakness. Current therapies encompass corticosteroids and other immunosuppressants and intravenous immunoglobulins (IVIg), however, none of these therapies are proven by randomized controlled phase 3 studies. There have been no large randomized clinical trials supporting the efficacy and safety of IVIg in DM.Objectives:The ProDERM study aimed to evaluate the efficacy and safety/tolerability of IVIg in DM patients in a double-blind, randomized, placebo-controlled, international multi-center, phase III clinical trial.Methods:The trial consisted of a double-blind, placebo-controlled First Period (16 weeks), in which adult patients with definite or probable DM (according to Bohan and Peter criteria) were randomized 1:1 to either high dose IVIg (2g/kg every 4 weeks) or placebo. Patients on placebo and patients without clinical worsening while on IVIg treatment entered the open label Extension Period (24 weeks) and received 2g/kg IVIg infusions every 4 weeks. To be included, subjects must have active disease with a manual muscle testing-8 (MMT-8) score < 142/150. Patients who showed clinical worsening (defined according to Oddis et al, 2013 - with slight adaptation) at 2 consecutive visits between week 8 and week 16 were switched to the alternate treatment arm.Primary endpoint was the proportion of responders in the IVIg vs. placebo arm at week 16, where response was defined per 2016 ACR/EULAR Myositis response criteria of at least minimal improvement [Total Improvement Score (TIS) ≥ 20 points)] and without clinical worsening at 2 consecutive visits up to week 16.Results:A total of 95 adult DM patients (mean age: 53 years; 75% females; 92% Caucasian) were enrolled, with 47 and 48 randomized to IVIg and placebo, respectively. Baseline clinical characteristics (including medical history and prior DM medication) were balanced between the 2 arms.The study met the primary endpoint at week 16, with the proportion of responders being significantly higher in the IVIg group (37/47; 78.7%) as compared to the placebo group (21/48; 43.8%; p-value 0.0008; Table 1).Table 1.Total Improvement Score – Analysis of Proportion of Responders at Week 16 (Full Analysis Set, N=95)TIS Responseoctagam 10%N=47PlaceboN=48Difference octagam 10% – placeboNumber (%) of responders37 (78.72%)21 (43.75%)Difference in response rates34.97[95% CI] p-valuea[16.70, 53.24] 0.0008aCochran-Mantel-Haenszel TestCI=confidence interval; N=number of patients; TIS=total improvement scoreIn the analysis of responders per improvement category at Week 16, a 45.2% higher response rate for at least moderate improvement (TIS ≥n40 points; p < 0.0001) and a 23.6% higher response rate for at least major improvement (TIS ≥060 points; p < 0.0062) was observed in the IVIG group as compared to the placebo group.The mean (SD) TIS was significantly higher in IVIg group [48.4 (24.4)] than in placebo arm [21.6 (20.2)] at week 16 (Fig 1).Figure 1.After switching to IVIG in the Extension Period the placebo group attained a similar response rate at Week 40 as did the IVIg treated patients at Week 16, i.e approx. 70% for minimal improvement.In line with the overall primary endpoint, secondary end points including all of the sub-components of TIS except muscle enzyme (MMT-8, MD global, Extramuscular global, patient global, HAQ,) as well as CDASI (Cutaneous Dermatomyositis Disease Area and Severity Index), also showed statistically significant improvement under IVIg treatment compared to placebo treatment.The safety and tolerability profile of IVIg was consistent with previously reported safety outcomes for IVIg administration.Conclusion:This is the first large international phase III randomized, placebo-controlled trial demonstrating the efficacy and safety of IVIg as a treatment for patients with DM.References:[1]Oddis, C. V. et al. Arthritis Rheum (2013), 65, 314–324Acknowledgements:Acknowledgments to all participating investigators, centers and patients and their familiesDisclosure of Interests:Rohit Aggarwal Consultant of: Q32, Alexion, Argenx, AstraZeneca, BMS, Boehringer Ingelheim, Corbus, Csl Behring, EMD Serono, Janssen, Kezar, Mallinckrodt, Kyverna, Octapharma, Orphazyme, Pfizer., Grant/research support from: BMS, Mallinckrodt, Pfizer, EMD Serono, Christina Charles-Schoeman Consultant of: Pfizer, Abbvie, Octapharma, Gilead, Regeneron-Sanofi, Grant/research support from: Bristol Myers Squibb, Pfizer, Abbvie, Octapharma, Joachim Schessl Speakers bureau: Octapharma, Grifols, CSL Behring, Consultant of: Octapharma, Zsuzsanna Bata-Csorgo Speakers bureau: Novartis, Sanofi-Genzyme, Ewopharma, Consultant of: Sanofi-Genzyme, Novartis, Ewopharma, Mazen Dimachkie Consultant of: ArgenX, Catalyst, Cello, CSL-Behring, EcoR1, Kezar, Momenta, NuFactor, Octapharma, RaPharma/UCB, RMS Medical, Sanofi Genzyme, Shire Takeda, Spark Therapeutics and UCB Biopharma., Grant/research support from: Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics, UCB Biopharma, Viromed/Healixmith., Zoltán Griger Speakers bureau: Abbvie, CSL-Behring, Eli-Lilly, Roche, Boehringer Ingelheim, Consultant of: Octapharma, Sergey Moiseev: None declared, Chester V Oddis Consultant of: EMD Serono; Alexion Pharmaceuticals, Inc, Grant/research support from: Genentech (Clinical trial support); Bristol Myers Squibb (Clinical trial support), Elena Schiopu Consultant of: Octapharma, Grant/research support from: Octapharma, Janssen (Johnson & Johnson), BMS, Pfizer, Abbvie, Jirˇí Vencovský Speakers bureau: Abbvie, Biogen, MSD, Pfizer, Roche, Sanofi, UCB, Consultant of: Abbvie, Boehringer, Eli Lilly, Octapharma, Gilead, Irene Beckmann Employee of: Octapharma, Todd Levine Shareholder of: Corinthian Reference Labs, CND Life Sciences, Consultant of: Grifols, Octapharma, Alexion, Elisabeth Clodi Employee of: Octapharma PPG, Vienna Austria, and the ProDERM Investigators: None declared

Background:AWARE is a real-world evidence-based (RWE) study evaluating the safety and efficacy of IV golimumab (GLM) and infliximab (IFX) in adults with RA.Objectives:Evaluate safety and efficacy of IV GLM and IFX in elderly AWARE participants.Methods:AWARE, a prospective non-interventional study (88 US sites), enrolled patients (pts) initiating either IV GLM or IFX. Pt management was at the discretion of treating rheumatologists. In a post hoc analysis, pts were grouped by age (Results:1270 pts were enrolled (685 IV GLM; 585 IFX). 1047 (82%) pts were female; mean age was 60 yrs (57% 1 rates of serious AEs (SAEs) and serious infections increased with age for both IV GLM and IFX; however, increases were more notable in IFX- than IV GLM-treated pts ≥65 yrs. The incidence of serious infections was highest in pts ≥75 yrs for both treatments, although small sample size may limit data interpretation. No increase in opportunistic infections, including Varicella, was observed in pts ≥65 vs Table 1.% of pts with ≥1 AE through W52 DBLIV GLMIFX≥65 yrs≥75 yrs≥65 yrs≥75 yrsPatients, n3513349137021546Discontinued due to AE8.5%12.6%16.5%15.1%17.7%21.7%AE52.4%58.4%57.1%63.5%66.5%71.7%Most common AEs (≥5% of pts in either treatment group)Nausea3.7%3.3%3.3%8.4%6.0%2.2%Worsening of RA5.4%4.5%3.3%7.3%7.0%4.3%Upper respiratory tract infection5.7%5.1%4.4%6.2%5.6%2.2%Pruritis1.4%2.4%3.3%6.8%2.8%2.2%Sinusitis7.1%3.3%0%3.8%3.7%2.2%Urinary tract infection4.8%5.1%5.5%4.3%5.1%6.5%SAE7.7%16.8%20.9%9.7%18.6%26.1%Infection30.5%27.2%27.5%32.2%28.8%32.6%Serious infection3.7%6.3%7.7%3.5%7.9%15.2%Neoplasms benign, malignant and unspecified0.6%2.7%1.1%0.8%2.3%6.5%Latent tuberculosis0.3%0%00.3%0%0%Opportunistic infection1.4%1.8%4.4%1.9%1.4%4.3%Infusion reaction5.1%2.7%1.1%17.3%8.8%8.7%Death0.3%2.4%2.2%0%2.3%6.5%Conclusion:Elderly RA pts receiving IV GLM or IFX in this RWE study demonstrated similar safety and efficacy as reported in Phase 3 trials.2,3 The higher rates of AEs, discontinuations due to AE, and SAEs (mainly serious infections) observed in pts ≥65 yrs are in line with increased safety events seen in elderly vs younger individuals in the general population. Rates of AEs, SAEs, and infusion reactions were higher for IFX vs IV GLM. Infusion reactions were more common in pts References:[1]Castle SC. Clin Infect Dis 2000;31:578–85.[2]Lipsky PE, et al. N Engl J Med 2000;343:1594-602.[3]Weinblatt ME, et al. Ann Rheum Dis 2013;72:381-9.Disclosure of Interests:Joy Schechtman: None declared, Aaron Broadwell Speakers bureau: Amgen, AbbVie, Eli Lilly, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Radius, Sanofi/Regeneron, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Celegene, Eli Lilly, Janssen, Novartis, Pfizer, and Sandoz, Shelly Kafka Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shawn Black Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Stephen Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Wayne Langholff Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Sergio Schwartzman Shareholder of: Amgen, Boston Scientific, Gilead, Medtronic, and Pfizer, Speakers bureau: AbbVie, Janssen, Eli Lily, Novartis, Pfizer, Regeneron, Sanofi, and UCB, Consultant of: AbbVie, Gilead, Eli Lilly, Janssen, Myriad, Novartis, Regeneron, Samsung, Sanofi, and UCB

Background:Current treatments for systemic sclerosis-associated interstitial lung disease (SSc-ILD) are characterised by different attributes such as mode of administration, adverse events (AE) and efficacy. Physicians and patients often have different perspectives on treatments, thus shared decision-making between patients and physicians is essential. An understanding of patients’ decision processes when weighing treatment attributes and the trade-offs they are willing to make is important for shared decision-making.Objectives:The study aimed to 1) identify relevant treatment attributes, 2) elicit patient preferences for these attributes and 3) quantify preference as relative attribute importance (RAI; a higher RAI indicates that more of the variability in patients’ responses may be explained by changes in the attribute); and maximum acceptable risk (MAR) of diarrhoea, nausea and/or vomiting (MAR is a trade-off measure that evaluates attributes in risk-equivalences as a unit of measurement).Methods:A discrete choice experiment (DCE) was created, based on a literature review, a patient advisory board, qualitative patient interviews, and a workshop involving SSc-ILD expert physicians. Seven SSc-ILD treatment attributes were identified: 1) mode of administration; 2) shortness of breath; 3) skin tightness; 4) cough; 5) tiredness; 6) risk of gastrointestinal tract (GIT) AEs; and 7) risk of serious and non-serious infections. The levels of AE risk were informed by frequencies observed in clinical trials and patient input during the interviews. The DCE was integrated into an online survey, which asked patients to make repeated choices between two alternatives described by varying levels of included attributes. Patients with SSc-ILD were recruited by physician referral from Switzerland, Norway, France, Germany and the USA. DCE data were analysed using a logit model, and RAI and MAR measures were calculated.Results:A total of 231 patients with physician-confirmed SSc-ILD (mean age 52.6±13.2 years; 54% diagnosed for >5 years) completed the survey. Patients with SSc-ILD mostly preferred twice-daily oral treatments (pPatients accepted an additional 21% risk (95% CI 13–29%) of GIT AEs if they could reduce the frequency of infusions from monthly to 6–12 monthly, or accepted an extra 15% (95% CI 7–23%) increase in risk if changing to an oral treatment twice daily. Among symptoms, an additional 28% (95% CI 20–36%) risk of GIT AEs was considered acceptable if the severity of patients’ persistent cough was reduced to a level that was easier to tolerate, even if it remained persistent. Similarly, a 37% (95% CI 28–46%) increase in the risk of GIT AEs was acceptable if it resulted in breathlessness during routine activities rather than breathlessness at rest. Finally, patients were willing to accept an additional 36% risk (95% CI 27–45%) of GIT AEs if it reduced their risk of non-serious infections from 30% to 15% and of serious infections from 10% to 5%.Conclusion:This is the first study to quantitatively elicit patients’ preferences for attributes of SSc-ILD treatments. Preferences were driven by safety, efficacy and technical considerations. Patients showed willingness to make trade-offs, providing a firm basis for shared decision-making in routine clinical practice.Disclosure of Interests:Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Gruppo Italiano Lotta alla Scleroderma (GILS), Fondazione Italiana per la Ricerca sull’Artrite (FIRA), New Horizon Fellowship, European Scleroderma Trial and Research (EUSTAR), Foundation for Research in Rheumatology (FOREUM)., Sebastian Heidenreich Consultant of: Sebastian Heidenreich, PhD is employed by Evidera Inc, a business unit of PPD. Evidera is a CRO that offers paid research services to pharmaceutical companies., Ashley Duenas Consultant of: Yes. I am an employee of Evidera which received funding from Boehringer Ingelheim for work related to this study., Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Merck Sharp & Dohme, Lilly, Consultant of: Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX, Lilly and Medscape, Grant/research support from: Boehringer Ingelheim, Armando Gabrielli Grant/research support from: Pfizer Bhering, Yannick Allanore Consultant of: Honorarium received from Boehringer, Medsenic,Sanofi, Menarini, Grant/research support from: Grants received from Alpine, Ose Immunogenetics, Emmanuel Chatelus: None declared, Jörg H.W. Distler Shareholder of: JHWD is stock owner of 4D Science, Consultant of: JHWD has consultancy relationships with Actelion, Active Biotech, Anamar, ARXX, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi and UCB, Grant/research support from: JHWD has received research funding from Anamar, Active Biotech, Array Biopharma, ARXX, aTyr, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, Novartis, Sanofi-Aventis, RedX, UCB, Eric Hachulla: None declared, Vivian Hsu Speakers bureau: I am a speaker for Boehringer Ingelheim Pharmaceuticals, Consultant of: with Boehringer Ingelheim Pharmaceuticals, Grant/research support from: Principal Investigator for several clinical trials, currently with Genentech, Corbus Pharmaceutical, and EICOS, Nicolas Hunzelmann Speakers bureau: Boehringer, Roche, Sanofi, Dinesh Khanna Shareholder of: Eicos Sciences, Inc (less than 5%), Consultant of: Paid Consultant for: Acceleron, Actelion, Abbvie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead, Galapagos, Genentech/Roche, GSK, Horizon, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis, and United Therapeutics, Grant/research support from: Research Grant support from: Immune Tolerance Network, Bayer, BMS, Horizon, Pfizer, Employee of: Leadership/Equity position – Chief Medical Officer, CiviBioPharma/Eicos Sciences, Inc – recieves a stipend for role as Chief Medical Officer, which would technically qualify as emplyoment., Marie-Elise Truchetet Speakers bureau: Abbvie, Lilly, Sobi, Boehringer, Paid instructor for: Lilly, Consultant of: UCB, Sobi, Abbvie, Grant/research support from: UCB, Gilead, Ulrich Walker Shareholder of: Bayer, NASDAQ, MSCI-World ETF’s, Speakers bureau: All companies producing pharmaceuticals used in AIDS, Paid instructor for: Roche, Abbvie, Novartis, Consultant of: All companies producing pharmaceuticals used in AIDS, Grant/research support from: Gilead, Abbvie, (in the last two years). Other companies in previous years., Margarida Alves Employee of: Boehringer Ingelheim, Nils Schoof Employee of: Employee of Boehringer Ingelheim International GmbH, Lesley Ann Saketkoo Speakers bureau: Boehringer Ingelheim, Actelion, Janssen, Mallinckrodt, United Therapeutics, Consultant of: Actelion, Boehringer Ingelheim, Bayer, Bristol Meyer Squibb, Corbus, EICOS, Janssen, Horizon, United Therapeutics, Inc, Grant/research support from: Mallinckrodt, United Therapeutics, Oliver Distler Speakers bureau: Boehringer Ingelheim, Medscape, IQone, Roche, Consultant of: OD has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years):Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: Kymera Therapeutics, Mitsubishi Tanabe

Background:The ACR Composite Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) was developed to measure the probability of improvement in response to treatment in patients with early diffuse cutaneous SSc (dcSSc), accounting for new/worsening cardiopulmonary involvement and/or renal crisis, and changes in modified Rodnan skin score, forced vital capacity, health assessment questionnaire disability index, and patient’s and physician’s global impressions. In patients with SSc-ILD, treatment response may be reflected as slower progression, stabilisation or improvement.Objectives:Using data from patients with dcSSc and ILD in the placebo group of the SENSCIS trial, we analysed the probability of improvement using the ACR CRISS score at week 52. We also evaluated whether the CRISS numerator could provide information on the spectrum of responses in this patient population.Methods:The SENSCIS trial enrolled subjects with SSc-ILD with onset of first non-Raynaud symptom ≤7 years before screening, FVC ≥40% predicted, and fibrotic ILD ≥10% extent on an HRCT scan. Subjects on prednisone ≤10 mg/day (or equivalent) and/or stable therapy with mycophenolate or methotrexate were allowed to participate. Subjects were randomised to receive nintedanib or placebo. Subjects were not randomised by use of mycophenolate. In patients randomised to receive placebo who had dcSSc and/or mRSS >15 at baseline, we analysed the ACR CRISS and its numerator at week 52 in subgroups by use of mycophenolate at baseline. Analyses were exploratory and descriptive.Results:Of 117 analysed subjects in the placebo group who had dcSSc and/or mRSS >15 at baseline, 60 (51.3%) were taking mycophenolate at baseline. Compared with patients not taking mycophenolate at baseline, those taking mycophenolate had a lower mean age (48.4 [SD 11.8] vs 53.1 [13.4] years), lower mean FVC % predicted (68.8 [17.0] vs 73.0 [14.6]), and a greater proportion were female (76.7% vs 71.9%); median time since first onset of non-Raynaud symptom was similar (3.9 vs 4.5 years, respectively) as was mean (SD) mRSS (16.5 [7.7] vs 15.9 [8.0], respectively). One patient (taking mycophenolate at baseline) had limited cutaneous SSc. At week 52, median (Q1, Q3) ACR CRISS score was 0.036 (0.001, 0.601) in subjects taking mycophenolate and 0.002 (0.000, 0.112) in subjects not taking mycophenolate at baseline, and mean (SD) ACR CRISS score was 0.28 (0.37) in subjects taking mycophenolate and 0.16 (0.31) in subjects not taking mycophenolate at baseline (Figure 1). In these groups, respectively, 25.0% and 14.0% of subjects had CRISS score >0.6 (considered improved) at week 52. The CRISS numerator provided a broader distribution of response values, but was not informative in this patient population.Conclusion:In exploratory analyses, among subjects with dcSSc and ILD who received placebo in the SENSCIS trial, the proportion considered improved at week 52 based on ACR CRISS score was numerically greater in patients taking than not taking mycophenolate at baseline. There remains a need for composite scores that provide better interpretation of the magnitude of response in patients with SSc.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Francesco Del Galdo Speakers bureau: Actelion and AstraZeneca, Consultant of: Actelion, AstraZeneca, Boehringer Ingelheim, Capella BioScience, ChemomAb and Mitsubishi Tanabe Pharma, Grant/research support from: Capella BioScience, Kymab and Mitsubishi Tanabe Pharma, Oliver Distler Consultant of: AbbVie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Bayer, Blade Therapeutics, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Glenmark Pharmaceuticals, Horizon (Curzion) Pharmaceuticals, Inventiva, IQVIA, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Target Bioscience, Topadur Pharma and UCB, Grant/research support from: Kymera Therapeutics and Mitsubishi Tanabe Pharma, Christopher Denton Speakers bureau: Boehringer Ingelheim, Corbus, Janssen, and Mallinckrodt Pharmaceuticals, Consultant of: Acceleron Pharma, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mallinckrodt Pharmaceuticals, Roche, Sanofi and UCB, Grant/research support from: Arxx Therapeutics, GlaxoSmithKline and Servier, Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals, Daniel Wachtlin Employee of: Currently an employee of Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Dinesh Khanna Shareholder of: Eicos Sciences, Inc. (less than 5%), Consultant of: Acceleron Pharma, Actelion, AbbVie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead Sciences, Galapagos NV, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis and United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health and Pfizer, Employee of: Chief Medical Officer- CiviBioPharma/Eicos Sciences, Inc.

CME/CNE Information Activity Available Online: To access the article, post-test, and evaluation online, go to http://www.cmscscholar.org. Target Audience: The target audience for this activity is physicians, physician assistants, nursing professionals, and other health-care providers involved in the management of patients with multiple sclerosis (MS). Learning Objectives: Apply new information about MS to a comprehensive individualized treatment plan for patients with MS Integrate the team approach into long-term planning in order to optimize rehabilitation care of patients with MS Accreditation Statement: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the Consortium of Multiple Sclerosis Centers (CMSC), Nurse Practitioner Alternatives (NPA), and Delaware Media Group. The CMSC is accredited by the ACCME to provide continuing medical education for physicians. The CMSC designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse Practitioner Alternatives (NPA) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NPA designates this enduring material for 1.0 Continuing Nursing Education credit. Laurie Scudder, DNP, NP, has served as Nurse Planner for this activity. She has disclosed no relevant financial relationships. Disclosures: Francois Bethoux, MD, Editor in Chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has received royalties from Springer Publishing and has received intellectual property rights from Biogen. Laurie Scudder, DNP, NP, has served as Nurse Planner for this activity. She has disclosed no relevant financial relationships. Scott D. Newsome, DO, MSCS (author), has served on scientific advisory boards for Biogen, Genentech, Novartis, and Genzyme, and has performed contracted research (institution received funds) for Biogen, Genentech, and Novartis. Philip J. Aliotta, MD, MSHA, CHCQM, FACS (author), has served on speakers' bureaus for Astellas Pharma, Actavis, Augmenix, and Allergan and has performed contracted research for Allergan. Jacquelyn Bainbridge, PharmD (author), has disclosed no relevant financial relationships. Susan E. Bennett, PT, DPT, EdD, NCS, MSCS (author), has served on speakers' bureaus for Acorda Therapeutics, Biogen, and Medtronic; has received consulting fees from and performed contracted research for Acorda Therapeutics; and is chair of the Clinical Events Committee at Innovative Technologies. Gary Cutter, PhD (author), has participated on Data and Safety Monitoring Committees for AMO Pharma, Apotek, Gilead Pharmaceuticals, Horizon Pharmaceuticals, Modigenetech/Prolor, Merck, Merck/Pfizer, Opko Biologics, Neuren, Sanofi-Aventis, Reata Pharmaceuticals, Receptos/Celgene, Teva Pharmaceuticals, NHLBI (Protocol Review Committee), and NICHD (OPRU Oversight Committee); has received consulting fees from and/or served on speakers' bureaus and scientific advisory boards for Cerespir, Genzyme, Genentech, Innate Therapeutics, Janssen Pharmaceuticals, Klein-Buendel Incorporated, MedImmune, Medday, Nivalis, Novartis, Opexa Therapeutics, Roche, Savara, Somahlution, Teva Pharmaceuticals, Transparency Life Sciences, and TG Therapeutics; and is President of Pythagoras, Inc., a private consulting company located in Birmingham, AL. Kaylan Fenton, CRNP, APNP, MSCN (author), has disclosed no relevant financial relationships. Fred Lublin, MD (author), has received consulting fees/fees for non-CME/CE activities from Bayer HealthCare Pharmaceuticals, Biogen, EMD Serono, Novartis, Teva Neuroscience, Actelion, Sanofi/Genzyme, Acorda, Questcor/Mallinckrodt, Roche/Genentech, MedImmune, Osmotica, Xenoport, Receptos/Celgene, Forward Pharma, Akros, TG Therapeutics, AbbVie, Toyama, Amgen, Medday, Atara Biotherapeutics, Polypharma, Pfizer, Johnson & Johnson, Revalesio, Coronado Bioscience, and Bristol-Myers Squibb; has served on speakers' bureaus for Genentech/Roche and Genzyme/Sanofi; has performed contracted research for Acorda, Biogen, Novartis, Teva Neuroscience, Genzyme, Xenoport, and Receptos; is the co–chief editor of Multiple Sclerosis and Related Disorders; and has an ownership interest in Cognition Pharmaceuticals. Dorothy Northrop, MSW, ACSW (author), has disclosed no relevant financial relationships. David Rintell, EdD (author), has received consulting fees from Novartis and has served as a patient education speaker for Teva Neuroscience. He started as a salaried employee of Sanofi Genzyme in November 2015. Dr. Rintell's work on this project was completed before he became a salaried employee of Sanofi Genzyme. Bryan D. Walker, MHS, PA-C (author), has served on scientific advisory boards for EMD Serono and Sanofi Genzyme and owns stock in Biogen. Megan Weigel, DNP, ARNP-C, MSCN (author), has received consulting fees from Mallinckrodt, Genzyme, and Genentech, and has served on speakers' bureaus for Bayer Corp, Acorda Therapeutics, Teva Neuroscience, Biogen, Mallinckrodt, Genzyme, Novartis, and Pfizer. Kathleen Zackowski, PhD, OTR, MSCS (author), has performed contracted research for Acorda Therapeutics. David E. Jones, MD (author), has received consulting fees from Biogen and Novartis, and has performed contracted research for Biogen. One anonymous peer reviewer for the IJMSC has performed contracted research (institution received funds) for Novartis, Chugai, and Biogen. Another reviewer has received consulting fees and served on speakers' bureaus for Biogen, Sanofi Genzyme, Genentech, EMD Serono, and Novartis. The third reviewer has disclosed no relevant financial relationships. Lori Saslow, MS (medical writer), has disclosed no relevant financial relationships. The staff at the IJMSC, CMSC, NPA, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships. Note: Disclosures listed for authors are those applicable at the time of their work on this project and within 12 months previously. Financial relationships for some authors may have changed in the interval between the time of their work on this project and publication of the article. Funding/Support: Funding for the Framework of Care consensus conference was provided by the Consortium of Multiple Sclerosis Centers, Mallinckrodt Pharmaceuticals, and Mylan Pharmaceuticals. Method of Participation: Release Date: December 1, 2016 Valid for Credit Through: December 1, 2017 In order to receive CME/CNE credit, participants must:Review the CME/CNE information, including learning objectives and author disclosures.Study the educational content.Complete the post-test and evaluation, which are available at http://www.cmscscholar.org. Statements of Credit are awarded upon successful completion of the post-test with a passing score of >70% and the evaluation. There is no fee to participate in this activity. Disclosure of Unlabeled Use: This CME/CNE activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. CMSC, NPA, and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of CMSC, NPA, or Delaware Media Group. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health-care professionals without first evaluating their patients' conditions, considering possible contraindications or risks, reviewing any applicable manufacturer's product information, and comparing any therapeutic approach with the recommendations of other authorities.

Introduction Multiple sclerosis (MS) is an autoimmune disorder with large annual costs. This study evaluated utilization and costs for the management of MS relapses with H.P. Acthar® Gel (repository corticotropin injection; Acthar; Mallinckrodt) compared to receipt of plasmapheresis (PMP) or intravenous immunoglobulin (IVIG) among patients with MS who experienced multiple relapses. Methods We identified patients with MS diagnoses who had relapses treated with intravenous methylprednisolone (IVMP), the first-line treatment for MS relapse. Patients who were treated for the subsequent relapses were eligible for the study. We analyzed 12- and 24-month healthcare utilization and costs among patients who received Acthar prescriptions compared to patients who were treated with PMP/IVIG using generalized linear and logistic regression models to calculate unadjusted and adjusted means and 95% confidence intervals. Results For the 12-month analysis, a total of 213 patients received Acthar prescriptions and 226 were treated with PMP or IVIG. Patients who received Acthar prescriptions were similar to those who received other treatments in terms of most demographic variables. Acthar recipients had fewer hospitalizations (0.2 vs. 0.4; P = 0.01) and received fewer outpatient services (29 vs. 43; P

Introduction The purpose of this study was to describe healthcare resource utilization and costs resulting from early (within 30 days of diagnosis) versus late (>30 days after diagnosis) treatment with prescriptions for H.P. Acthar® Gel (repository corticotropin injection; Acthar; Mallinckrodt) to manage infantile spasms (IS). Methods We included all patients in the Truven Health MarketScan® Commercial Claims and Encounters Database and the Truven Health MarketScan Multi-State Medicaid Database who were diagnosed with IS from 2007 to 2012. We performed unadjusted and adjusted regressions examining the relationship between healthcare resource utilization variables and their associated costs to compare outcomes in the early and late Acthar users. Results A total of 252 patients with IS who received Acthar fit our study criteria; 191 (76%) were early Acthar users. In adjusted analyses, we found that early Acthar use was associated with, on average, 3.8 fewer outpatient services (99% CI 0.7–6.7 fewer services). We did not find significant associations between early prescriptions for Acthar and number of hospitalizations, emergency room visits, prescription medications filled, or total costs of health services. Conclusion Patients prescribed Acthar within 30 days of their IS diagnoses tended to have fewer outpatient services performed compared to patients prescribed Acthar later in the disease process. Although additional research is needed to confirm these exploratory findings, physicians may consider early treatment with Acthar to manage IS. Funding This study was funded by a grant to the University of Washington from Mallinckrodt Pharmaceuticals. Electronic supplementary material The online version of this article (doi:10.1007/s12325-016-0361-2) contains supplementary material, which is available to authorized users.

Background A randomised study was conducted on the number of attempts made during the conventional endotracheal intubation of a mannequin using two polyvinyl (PVC) tracheal tubes, apparently similar but from different manufactures: Intersurgical (IS; Intersurgical S.L., Madrid, Spain) and Mallinckrodt (ML; Mallinkrodt Medical S.A., Madrid, Spain). Methods A total of 26 anaesthesiologists, in randomly established order (generated by Epidat 3.1) intubated a mannequin twice using a different tube each time. The tubes were masked by painting them to prevent recognition. The main outcome of the study was to compare the number of attempts needed to complete the manoeuvre for each tube. Data on intubation time and failed intubations were also collected. Results The number of attempts with the ML tube was significantly lower than with the IS tube. Intubation was completed on the first attempt with the ML tube in 93.3% of cases, while using the IS tube the percentage fell to 30.8% (Fisher exact test, p Conclusions The PVC tube from the ML manufacturer was superior when compared with the IS, the latter was also associated with a larger number of attempts to complete intubation using a conventional Macintosh blade.

The authors examined the association between relational health and student adjustment to college. Data were collected from 138 undergraduate students completing their 1st semester at a large university in the mid-southern United States. Regression analysis indicated that higher levels of relational authenticity were a predictor of success during the I st semester; no significant findings were detected for relationships between relational empowerment and engagement constructs and adjustment. Suggestions for promoting relational development are provided. Keywords: relational health, authenticity, adjustment, college ********** Completion of a college degree in today's society is intricately linked to economic and social well-being across the life span (Pascarella & Terenzini, 2005). Despite an unprecedented rise in college entry, graduation rates remain strikingly low. Reports by the College Board Advocacy and Policy Center (2012) indicate that approximately 54% of students attending 2- and 4-year colleges do not persist to graduation and depart college failing to earn a degree or certification of any type. Although some students depart college because of an involuntary event that interferes with degree completion, decades of research (Pascarella & Terenzini, 2005) indicate that variables affecting student perseverance in college are systemic, constant, and, in most cases, preventable (Pritchard & Wilson, 2003). From a systems perspective, college attrition is most precipitous during the first semester, leading researchers to conclude that student adjustment is, in part, a function of how well students acclimate to campus life (Calaguas, 2011; Gerdes & Mallinckrodt, 1994; D. Lee, Olson, Locke, Michelson, & Odes, 2009; Martin, Swartz-Kulstad, & Madson, 1999; Trotter &: Roberts, 2006). Models of student adjustment proffered to explain this phenomenon identity four distinct yet theoretically related components: academic adjustment, social adjustment, personal-emotional adjustment, and institutional attachment. Merit for the fourfold adjustment model has been empirically established (Baker & Siryk, 1999; Pascarella & Terenzini, 2005; Swail, Redd, & Perna, 2003), yet no single factor, or set of these factors, can adequately account for the loss of students from the college pipeline (Pascarella & Terenzini, 2005; Pritchard & Wilson, 2003). The shortcoming of extant models to predict patterns of student attrition accurately has prompted researchers to consider alternative variables that exert influence across the traditional domains of college adjustment (Lenz, 2014; Pritchard & Wilson, 2003). Studies conducted through a feminist lens have added a fresh dimension to existing theory by illuminating how relational strength can positively affect college-going experiences (LaBrie et al., 2008; Lenz, 2014; Liang, Tracy, Kenny, Brogan, & Gatha, 2010; Liang & West, 2011). Anchored in the feminist tradition, relational cultural theory (RCT) contends that women's relationships, based on a mutual acceptance of self, serve as a natural buffer to stress and provide the platform for growth across the life span (Jordan, 1997; Miller, 1976). Although RCT developed in the context of women's studies, more recent studies have demonstrated the applicability of this model for examining characteristics of men's relational well-being (Liang, Tracy, Glenn, Burns, & Ting, 2007). In the present study, by exploring components of college students' adjustment (academic, social, personal-emotional, and institutional), we attempted to extend emergent knowledge to the quality of students' relational health. Using a mixed-gender sample, we theorized that adjustment to college during the first semester is mediated by the existence of growth-fostering relationships, as measured by core dimensions of relational health: engagement, authenticity, and empowerment (Liang, Tracy, Taylor, Williams, & Jordan, 2002). …

Mallinckrodt et al. developed the measure Everyday Multicultural Competencies and combined its items with those in the Scale of Ethnocultural Empathy to form a new scale to assess college multicultural programming. Mallinckrodt, Miles, and Recabarren used this scale as an example to provide recommendations for using focus groups and item response theory (IRT) in instrument development. In this commentary, we focus on two areas of major concerns: (a) paradigmatic and methodological issues pertaining to the use of mixed methods research design, focus groups, and IRT in developing psychological instruments aiming to assess multicultural constructs and (b) the importance of attending to the multidimensionality and context of these constructs. We believe it is important for future researchers to provide a thorough accounting of these paradigmatic and methodological issues in their studies and a clear explication of the target construct in scale development research.

As scale development researchers, we have followed Mallinckrodt and colleagues’ work over recent years with significant interest. The scale development process can be challenging and typically demands a large investment of time. However, the end of the process is rewarding when the resulting scale is psychometrically sound. Mallinckrodt, Miles, and Recabarren’s contribution in this volume of The Counseling Psychologist attempted to help integrate the use of item response theory in the scale development process. Although they are to be commended for this endeavor, there are some limitations inherent in their contribution. This reaction provides a critical evaluation of their work to augment their recommendations.

Application of nitrous oxide during anesthesia causes an increase in tracheal tube cuff pressure over time. The purpose of this study was to investigate the effect of an increase in cuff pressure on 3 types of tube (the Portex, Mallinckrodt, and Parker) commonly used for nasotracheal intubation. A cylindrical vessel was used to simulate a trachea. Cuff pressure was set at 0 cmH2O (R0) or 20 cmH2O (R20) at room temperature, or at 20 cmH2O (H20), 40 cmH2O (H40), 60 cmH2O (H60), or 80 cmH2O (H80) in 38°C hot water and pressure applied for 30 min. The value obtained at R0 was used as a reference (100%) and the rate of change under each condition determined. No change was observed at R20 in any of the 3 groups. In 38°C hot water, internal diameter in the Portex group decreased by 5.4% at H20 and 7.3% at H40, while that in the Mallinckrodt group decreased by 6% at H40. No significant change was observed in internal diameter in the Parker group, even when cuff pressure was increased. The internal diameter in the Portex group was the smallest at all cuff pressures in hot water. When the nasotracheal intubation tubes selected were placed in a simulated trachea and cuff pressure increased, internal diameter in the Portex and Mallinckrodt groups decreased.

This book deals mostly with longitudinal clinical trial data, but also with the related issue of imputing missing data. The book is an excellent resource overall, as it is fairly comprehensive, wel...

Curative potential of allogeneic hematopoietic cell transplantation (aHCT) in myeloid malignancies is principally related to the graft versus leukemia (GvL) effect exerted by donor-derived immune effectors on leukemic cells. However, different pathways may drive post-transplant relapse, including perturbation/attenuation of T cell-mediated GvL responses. For example, decreased expression of HLA alleles has been described in post-aHCT relapse.1 This could be due to down-regulation of HLA or 6p HLA locus deletion. However, the occurrence of chromosome 6p uniparental disomy (UPD) along with del6p (first described by our group in the context of aplastic anemia)2 suggests that HLA loss of heterozygosity (LOH) and inherent loss of one allele (presenting immunodominant peptides) may be a significant contributor to leukemic relapse either directly, causing decreased HLA expression or as additive effect to HLA down-regulation. In relapses after haploidentical or mismatched aHCT, LOH of mismatched allele has been described.3 Here, we hypothesize that not only copy neutral LOH or haploinsufficient HLA expression but also defective function due to HLA mutations may lead to immune escape from GvL. Such a mechanism would involve the loss of an allele responsible for the presentation of an immunodominant antigenic peptide. Moreover, unlike relapse due to the acquisition of additional myeloid mutations, HLA mutant relapse would also acquire resistance to donor lymphocyte infusion (DLI) therapy. In order to dissect the immunogenomic mechanisms leading to leukemic immune-evasion, we performed a comprehensive genetic analysis of specimens sequentially collected from a cohort of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) relapsed after aHCT. Specifically, we applied a deep-targeted NGS panel to study HLA region along with 173 genes known to have a role in leukemogenesis and cancer ontogeny. So far, 57 paired/serial biospecimens from 25 transplanted patients have been analyzed (25 samples at AML/MDS diagnosis, 25 at the moment of relapse after aHCT and 7 samples at relapse after chemotherapy) Overall, we found the acquisition of 8 disruptive HLA somatic mutations in 6 patients at post-transplant relapse (24%), 4 in class I and 4 in class II loci. None of those events were found in samples at diagnosis or at post-chemotherapy relapse, suggesting the possibility of an "immune-escape relapse". Those somatic hits accounted for 4 intronic indels, 1 frameshift insertion, one splicing site and 2 point mutations in 3′ and 5′ untranslated regions (UTRs). Median variant allele frequency (VAF) was 17% (range 2-58%). Of note is that all HLA mutant patients received a matched aHCT (4 from related and 2 from a 10/10 matched unrelated donors) suggesting that this mechanism is independent from the deletion and the loss of an immune privileged mismatched allele. Interestingly, median time to relapse was 514 (range 119-935) days for HLA-mutated patients vs 126 (62-543) for HLA wild type cases (p=.00042), consistent with the hypothesis that the establishment of immune-tolerance, and the presence of a GvL effect (less likely in early relapses) are required for the selection of those mutations. When somatic genotype of these patients prior and after transplant was studied, we found that post-aHCT relapses were associated in most cases with a new genomic configuration with either loss of previous events or acquisition of new subclonal mutations in myeloid or cancer related genes (in 17/25 cases). However no difference was seen in terms of number and patterns of new events among the HLA mutated and HLA wild type patients. Results shown here represent an important proof-of-concept for the role played by somatic mutations in HLA genes in the setting of post-aHCT AML/MDS relapses. These events, in analogy to the deletion or copy neutral LOH, may promote immune escape relapse resistant to immunologic manipulations and may coexist or be an alternative pathway to the progression/relapse characterized by acquisition of myeloid subclonal driver mutations. In that context, HLA mutations would be considered facilitator lesions. Disclosures Hsi: CytomX: Consultancy, Honoraria; Eli Lilly: Research Funding; Abbvie: Research Funding; Miltenyi: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Hamilton:Syndax Pharmaceuticals: Consultancy, Honoraria. Carraway:Abbvie: Other: Independent Advisory Committe (IRC); BMS: Consultancy, Other: Research support, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Takeda: Other: Independent Advisory Committe (IRC); ASTEX: Other: Independent Advisory Committe (IRC). Majhail:Incyte: Honoraria; Mallinckrodt: Honoraria; Nkarta Therapeutics: Honoraria; Anthem, Inc.: Consultancy. Maciejewski:Alexion, BMS: Speakers Bureau; Novartis, Roche: Consultancy, Honoraria.

Background: T cells in CTCL are functionally exhausted and are characterized by the expression of immune inhibitory molecules such as PD1 and PD-L1 (Cancer Immunol Res 6; 2018). These findings justify the evaluation of immune checkpoint inhibition to reverse T cell exhaustion in CTCL. We initiated a phase 1/2 clinical trial of lenalidomide and durvalumab to determine the safety and efficacy of this regimen. Durvalumab is a human monoclonal antibody with high affinity and selectivity for PD-L1, targeting exhausted T cells and distinct cells within their environment. Lenalidomide, an oral immunomodulatory drug (IMiD) and analog of thalidomide, has previously shown activity in CTCL (Blood 123; 2014). Durvalumab may restore an anti-tumor immune response, and the combination of durvalumab and lenalidomide may enhance immune checkpoint blockade-induced immune responses. Associations between immune checkpoints, gene expression profile and the clinical efficacy of durvalumab/lenalidomide combination were evaluated. The primary objectives were to determine the recommended phase 2 dose of lenalidomide in combination with durvalumab and safety with primary endpoint of toxicity (using CTCAE 4.03). Secondary end points included objective response rate (ORR) and median duration. Relationships between gene expression profile (GEP), PD-L1 expression, and antitumor activity were exploratory end points. Methods: A Phase 1 portion (NCT03011814) is ongoing to evaluate the safety and tolerability of the durvalumab and lenalidomide combination. Pts are enrolled in sequential cohorts to receive durvalumab (fixed dose at 1500 mg) and dose escalation of lenalidomide (dose level 1 = 10 mg for all cycles; dose level 2 = 10 mg for cycle 1, 15 mg for all subsequent cycles; dose level 3 =10 mg for cycle 1, 15 mg for cycle 2, and 20 mg for all subsequent cycles) to characterize safety, efficacy and antitumor activity. Serial skin samples were collected to assess the impact on the tumor microenvironment and anti-tumor activity. Results: Ten pts. were evaluable for toxicities. Nine patients were evaluable for response with three patients at each dose level. 8 males/2 females, age 29-59 y, with refractory/advanced CTCL, clinical stages IB (1), IIA (3), IIB (4), IIIA (1), and aggressive epidermotropic CD8+ CTCL (1) and a median of prior systemic treatments of 3 (range, 2-4) have been enrolled. Median follow up time was 12 (range, 3-24+) months. No serious AEs or DLTs were observed during the DLT evaluation period (cycles 1-3). The most frequently reported AEs were fatigue (n=7), skin pain (n=4), chills (n=3), anemia (n=3), and leukopenia (4). One grade 3 maculopapular rash (possibly due to lenalidomide) was observed, all other treatment-related AEs were grade 1/2 in severity. Median cycles of treatment were 7 (range, 3-20+) months. Median duration of response was 4 (range, 1- 21+) months. Six pts achieved PR, while 3 pts maintained stable disease. Three pts remain on treatment. Expression panels of several checkpoints (PD1, PD-L1 & ICOS) (Cycle1 Day1 vs Cycle 2 Day15) were analyzed. Detectable levels of PD-L1 but low levels of ICOS are observed in responding pts vs. high PD-L1 and ICOS levels in non-responders. GEP highlights downregulation of TNF-alpha signaling via NFkB, IFN-gamma, and PI3-AKT-mTOR signaling pathways among other pathways. Conclusions: Durvalumab/lenalidomide has significant clinical activity in refractory/advanced CTCL, which will be formally evaluated in the Phase 2 portion. Responses were durable and ongoing, and treatment was well tolerated. Dose escalation is up to lenalidomide 20 mg daily. Our preliminary results from pts on trial demonstrated that immune signatures on skin biopsies at baseline may be predictive of response to checkpoint blockade and yield insights into mechanisms of therapeutic resistance. Disclosures Querfeld: Bioniz: Membership on an entity's Board of Directors or advisory committees, Other: Investigator; Soligenix: Other: Investigator; Celgene: Other: Investigator, Research Funding; City of Hope Cancer Center and Beckman Research Institute: Employment; Medivir: Consultancy; Trillium: Consultancy, Other: Investigator, Research Funding; miRagen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Investigator; Kyowa: Membership on an entity's Board of Directors or advisory committees, Other: Investigator; Eisai: Other: Investigator; Elorac: Other: Investigator, Research Funding; Helsinn: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Investigator. Palmer:Gilead Sciences: Consultancy. Zain:Spectrum: Consultancy; Seattle Genetics: Consultancy.

Introduction Intestinal graft-versus-host disease (GvHD), following allogeneic hematopoietic stem cell transplantation (allo-HSCT), has a high mortality rate and a reduced life-expectancy. In this context, failure to respond to steroid therapy is associated with limited further therapeutic options, thereby representing an unmet medical need. Aiming at restoring microbiome functions, fecal microbiota transfer (FMT) has proved to be a promising treatment modality in this challenging clinical setting, with recent studies reporting favorable results in steroid refractory-acute GVHD (SR-aGvHD) patients. Here we report on the use of a next-gen FMT product "MaaT013", a standardized, pooled-donor, high-richness microbiota biotherapeutic, used to treat 29 patients with intestinal aGvHD as part of a compassionate use/expanded access treatment program. Patients and methods Twenty-nine allo-HSCT recipients with steroid-dependent or SR intestinal GvHD (classical aGVHD n=22, late-onset aGVHD n=2; aGvHD with overlap syndrome n=5) were treated with MaaT013 biotherapeutic as part of a compassionate use/expanded access treatment program of the developer MaaT Pharma. These patients had previously received and failed 1 to 5 lines (median 3; 22/29 received ruxolitinib) of GvHD systemic treatments. Each patient received 1 to 3 doses (median: 3; total doses administered: 71) of MaaT013, a 150 mL bag, by enema (n=28) or nasogastric tube (n=1). GI-GvHD response was evaluated 7 days after each administration and 28 days after the first dose. Prepared under Good Manufacturing Practices, MaaT013 biotherapeutics are characterized by a highly consistent richness of 455 ±3% Operational Taxonomic Units and an Inverse Simpson index greater than 20. Batch release specifications are based on potency (viability), identity (diversity), and purity (microbiological safety testing and proportion of proinflammatory species), ensuring the desired consistency across batches. Results We observed a GI overall response rate of 59% (17/29) at day 28 after first dosing, including 9 complete response (CR), 6 very good partial response (VGPR), and 2 partial response (PR). Considering the best GI response achieved, 20/29 patients (69%) achieved at least a PR, with 9 CR, 8 VGPR and 3 PR. Among the 29 treated patients, 16 were still alive at last follow-up (median follow-up (FU): 131.5 days; range [28; 413]) and 6 months overall survival was 54%. Among the 9 patients achieving CR, all were still alive at last follow-up (median FU: 197 days; [49; 301]) and were able to taper or stop steroids and immunosuppressants. Among these 9 patients, three patients presented GI symptom recurrence between 2 and 3 months after dosing. In 2 patients, this recurrence occurred after heavy antibiotic treatment, one of them received an additional MaaT013 dose and achieved a second CR. Of note, among these 9 patients, mild chronic mucosal GvHD symptoms persisted in one patient, and molecular relapse of hematologic malignancy was observed in another. The safety of the MaaT013 microbiota biotherapeutic was satisfactory for all patients. One patient developed "possibly related" sepsis one day after the third dosing but no pathogen was identified in blood cultures, and the patient recovered after a course of antibiotics. Another patient developed C. difficile diarrhea 24 hours post-administration. This was not causally related to MaaT013, as C. difficile testing was negative in the MaaT013 lot. Nosocomial transmission was suspected as the cause as several patients with C. difficile infection were hospitalized in the same unit during this period. Conclusions We herein report for the first time the treatment of 29 patients with steroid-dependent or SR intestinal aGvHD using a full ecosystem, standardized, pooled-donor, high-richness biotherapeutic. The overall response rate was 59% with the off-the-shelf MaaT013 product, which was shown to be safe and effective in these heavily pre-treated and immunocompromised patients, warranting further exploration of the full ecosystem microbiota restoration approach. Disclosures Malard: Astellas: Honoraria; JAZZ pharmaceutical: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Keocyt: Honoraria; Theralos/Mallinckrodt: Honoraria; Biocodex: Honoraria. Plantamura:MaaT Pharma: Current Employment. Mohty:BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Background:The treatment goal in rheumatoid arthritis (RA) is sustained remission and prevention of RA flares [1]. While targeted biologics have improved disease outcomes, almost one-third of patients (pts) discontinue treatment by 1 year and 50% by 2 years, with lack of efficacy as the most common reason [2]. Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogues and other pituitary peptides and is an agonist for all 5 melanocortin receptors (MCRs). Activation of MCRs by RCI has been shown to have direct and indirect anti-inflammatory and immunomodulatory effects. RCI is indicated for adjunctive therapy for short-term administration in RA flares or uncontrolled disease [3].Objectives:To characterize RA pts that initiate RCI therapy and identify predictors of RCI initiation, compared to biologic disease-modifying antirheumatic drugs (DMARDs).Methods:This retrospective cohort study identified pts with ICD-9/10 diagnosis for RA over an 11-year period (2008-2018) in a large claims database (Truven MarketScan®). Adults with ≥1 claim for RCI (RCI cohort) or ≥1 RA-related biologic claim but no RCI (non-RCI cohort) were selected and characterized by demographics, disease severity (Claims-based Index for RA Severity, CIRAS), comorbidities (Charlson Comorbidity Index, CCI), treatment patterns, and healthcare resource utilization in the 12-month baseline (BL) period prior to their index date (i.e., the 1stRCI claim or last claim for biologic for non-RCI cohort). Predictors of RCI initiation were identified by multivariable logistic regression, controlling for demographics and BL characteristics.Results:A total of 393 pts initiated RCI therapy while 188,062 initiated biologic treatment with no RCI claims. At BL, cohorts were similar with respect to mean age (~56 years), gender (76-79% female), and insurance type (79-80% commercial). Cohorts differed by region, plan type, and index year. Compared to non-RCI patients, the RCI cohort had significantly higher CCI and CIRAS scores; higher use of traditional DMARDs (65.6% vs. 61.9%), corticosteroids (CS, 91.3% vs 68.8%), prescription nonsteroidal anti-inflammatory drugs (NSAIDs, 66.9% vs 58.5%), and opioids (67.7% vs 47.5%), but lower biologic use (45.8% vs. 87.7%) (all pRCI therapy initiation was most significantly impacted by treatment patterns, including number of DMARDs, CS, and opioids tried in the previous year (Figure 1). Corticosteroid use was the strongest predictor of RCI initiation, especially extended use at any dose (OR≥2.6) and extended use of the highest doses (>15 mg/day, OR=8.5), present in 21% of the RCI cohort (Figure 1). Drug benefit generosity (proportion of out-of-pocket costs) was also associated with RCI initiation in any plan qualified as better than “below average” (OR=2.1-2.9). Anemia, renal disease, and Sjogren’s syndrome were also associated with higher odds of RCI initiation (OR=1.4-2.1).Conclusion:RA pts initiating RCI therapy were prescribed a greater number of traditional DMARDs, CS, and opioids in the previous 12 months compared to non-RCI pts, and have evidence of more severe disease and comorbidities. Extended and high dose CS use were the factors most associated with RCI initiation.References:[1]Smolen JS, et al. Ann Rheum Dis. 2017;76:960–977[2]Strand V, et al.. Rheumatol Ther. 2017;4(2):489-502.[3]Acthar Gel (repository corticotropin injection; perscribing information). Mallinckrodt ARD LLC, Bedminster, NJ 07921 USA. 2019.Disclosure of Interests:Kyle Hayes Employee of: Mallinckrodt ARD, LLC, Mary Panaccio Employee of: Mallinckrodt Pharmaceuticals, Huanxue Zhou Consultant of: I am full time employee in KMK Consulting Inc. and providing consulting service to Mallinckrodt, Mohammed Fahim Consultant of: I am full time employee in KMK Consulting Inc. and providing consulting service to Mallinckrodt

Background:Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD)1,2, but the relationship to fibrosis remains uncertain3. Moreover, it is not known whether lowering serum urate will affect the course of NAFLD. The availability of data from two randomized trials of pegloticase, a pegylated recombinant mammalian uricase, that profoundly decreases serum urate afforded the opportunity to test the hypothesis that lowering urate might improve NAFLD.Objectives:To determine whether treatment of chronic refractory gout patients with pegloticase was associated with improvement in NAFLD determined by Fibrosis 4 index (Fib4).Methods:Databases from patients with chronic refractory gout who participated in two randomized 6 month clinical trials (RCTs) of pegloticase were analyzed4. Sub-sets who had persistent urate lowering to levels 5,6calculated from measurements of AST, ALT, platelet count and age (Age x AST/platelets x √ALT). A Fib4 value of 1.3 is an indication that further evaluation of liver disease is warranted.Results:At baseline, the mean Fib4 values were 1.40 ± 0.86 in pegloticase responders and 1.04 ± 0.53 in subjects receiving placebo. As shown in figure 1, subjects receiving placebo exhibited a change of 0.26 ± 0.41 in the Fib4 score over the six months of the RCTs compared with 0.13 ± 0.62 in the pegloticase responders (p=0.048; by linear regression). When only the subjects with a Fib4 value > 1.3 were considered, a significant difference in the change in the Fib4 values over the 6 months of the trial between pegloticase responders and those receiving placebo was also observed (-0.15 ± 0.67 vs 0.37 ± 0.42, p=0.004, by linear regression). The correlations between serum urate area under the curve (AUC) over the 6 months of the trial and the change in Fib4 value was rs=0.33, p=0.0.0004 (Spearman rank-order correlation coefficient). Finally, multiple linear regression analysis indicated serum urate AUC (as a surrogate measure for group) is the main contributor to the change in Fib4 (p=0.018 by linear regression).Conclusion:The data are consistent with the conclusion that persistent lowering of serum urate had a significant impact on Fib4 levels, implying a possible effect on the course of NAFLD. The results support a more complete analysis involving biopsy examination of the impact of urate on liver inflammation and fibrosis.References:[1]Yang C et al. PlosOne2017; 12:e0177249[2]Jaruvongvanich V et al. Eur J Gastroenterol Hepatol 2017; 29:1031[3]Jaruvongvanich V et al. Eur J Gastroenterol Hepatol 2017; 29:694[4]Sundy JS, et al. JAMA. 2011; 306 (7):711-20[5]Sterling RK et al. Hepatol 2006; 43:1317[6]Shah AG et al. Clin Gastroenterol Hepatol 2009;7:1104Disclosure of Interests: :Naomi Schlesinger Grant/research support from: Pfizer, Amgen, Consultant of: Novartis, Horizon Therapeutics, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Anthony Yeo Employee of: Horizon Therapeutics, Peter Lipsky Consultant of: Horizon Therapeutics

Background:Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides approved for short-term adjunctive treatment of rheumatoid arthritis (RA).Objectives:This two-part, international, multicenter, placebo (PBO)-controlled study assessed the efficacy of RCI in persistently active RA patients (pts) using clinical and patient-reported outcome measures (PROMs) (ClinicalTrials.govNCT02919761).Methods:Adults ≥18 years with persistently active RA (DAS28-ESR >3.2) despite disease-modifying anti-rheumatic drug and glucocorticoid use received open-label RCI (80 U) subcutaneously 2x/week (BIW) for 12 weeks (Part 1). Pts with DAS28-ESR Results:In the mITT-P (N=259), 62.9% (pp=0.035) vs. PBO (43.4%). Clinically significant improvements in PROMs from BL were observed through W12 and sustained to W24 (Table 1), with mean changes exceeding the reported minimal clinically important difference thresholds (MCIDs) for each.Conclusion:RCI for persistently active RA resulted in clinically significant improvements in efficacy endpoints and PROMs for up to 6 months in pts who continued and discontinued RCI after 3 months of initial therapy.References:Acknowledgments:Editorial support was provided by MedLogix Communications, LLC, Itasca, Illinois, under the direction of authors and funded by Mallinckrodt Pharmaceuticals.Disclosure of Interests:Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Daniel Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Consultant of: AbbVie, Actelion, Amgen, BMS, Cytori Therapeutics, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), George Wan Employee of: Mallinckrodt Pharmaceuticals, Mary Panaccio Employee of: Mallinckrodt Pharmaceuticals, Jingyu Liu Employee of: Mallinckrodt Pharmaceuticals, Julie Zhu Employee of: Mallinckrodt Pharmaceuticals, Richard Brasington Speakers bureau: Amgen, Mallinckrodt Pharmaceuticals, Novartis, and Pfizer

Background:Gout is the most common form of inflammatory arthritis and its economic burden is substantial, with estimates for the overall cost exceeding $20 billion (US) annually. Contributing to the economic burden are hospital admissions and iatrogenic events associated with pharmacotherapy. Identification of modifiable risk factors would be an important contribution to clinical practice.Objectives:The aim of this study was to identify opportunities for enhancing gout care in patients presenting to the Emergency Department (ED) with gout flares.Methods:This retrospective cohort study used data from electronic medical records (EMR) at a large community hospital. All consecutive patients visiting the medical center ED with a primary diagnosis of gout from 1/1/2016 to 7/1/2019 were included. Patients were then followed for 90 days to determine whether they were readmitted to the ED for any reason. A chart review identified whether they were on appropriate medications in terms of gout flare management. All data were summarized using descriptive statistics. A multiple logistic regression was constructed to identify risk factors for ED utilization within 90 days of the index visit.Results:A total of 214 patients were included in the analysis. Most patients were male (79%), mean age was 59.4 ± 15.6 years, and mean Charlson comorbidity index was 0.5 ± 1.14. The most common medications prescribed during the ED visit included NSAIDs (41.6%), opioids (28%), corticosteroids (26.6%), and colchicine (21%). Allopurinol and febuxostat were initiated in the ED in 4.7% and 0.9%, respectively. Discharge medications for the management of gout included NSAIDs (37%), corticosteroids (34.6%), opioids (23.8%), colchicine (14%), febuxostat (7%), and allopurinol (6.5%). Of the patients sent home with an opioid, 40% were newly prescribed. An anti-inflammatory medication was not prescribed in 29.6% of patients discharged from the ED. Readmission within 90 days was recorded in 16.8% of patients. Of these readmissions, 33.3% were gout-related and 11.1% were cardiac related.After adjusting for age and comorbidity index, patients receiving colchicine were 2.8 times more likely (OR, 2.81; 95% CI, 1.12 to 7.02; p=0.027) to return to the ED within 90 days. The most common cause of readmission in this subset was gout-related (54.5%).Conclusion:Nearly 30% of patients were discharged from the ED without an anti-inflammatory medication, whereas initiation of urate lowering therapy was rare. Opiates were used frequently, but the indication was uncertain. Only 5.6% of subjects revisited the ED for gout-related diagnoses in the subsequent 3 months. Colchicine prescription was associated with an increased risk of gout-related ED utilization within 90 days. Treatment of gout in the ED is sub-optimal and often does not follow established guidelines.Disclosure of Interests: :Luigi Brunetti Grant/research support from: Astellas Pharma, CSL Behring, Consultant of: Horizon Foundation of New Jersey, Janaki Vekaria: None declared, Peter Lipsky Consultant of: Horizon Therapeutics, Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon

Background:Dermatomyositis (DM) is a systemic, autoimmune disease affecting the skin and proximal skeletal muscles. A subset of DM patients present with subclinical or resolved muscle involvement but continue to have skin disease. In these cases, first and second line treatments including glucocorticoids are sometimes insufficient for controlling the disease, necessitating escalation of treatment. Several recent studies have investigated the response of Tofacitinib, an oral Janus Kinase inhibitor approved for the treatment of rheumatoid arthritis, in DM patients and patients with inflammatory skin diseases.Objectives:Due to the reported ability of JAK inhibitors to suppress type 1 interferon (IFN) signaling, which is suspected to be upregulated in DM, we evaluated the efficacy of treatment with Tofacitinib in four refractory DM patients.Methods:Four patients with dermatomyositis without evidence of current muscle involvement began treatment with Tofacitinib 11 mg daily after they had failed or had adverse effects to first and second line immunosuppressive agents. Their medical records were reviewed at 0, 3, and 6 months, with improvement measured using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score. Throughout their treatment they were additionally monitored for improvement in markers of inflammation and the necessity for concomitant treatments. Patients were monitored for adverse effects to Tofacitinib treatment.Results:All four patients within the case series showed significant improvement of their cutaneous disease activity (CDASI scores improved by 8-15 points) over the first 6 months, with three of the four having achieved minimal clinically improved difference of >= 5 point by three months. Based on the CDASI, three of the cases’ disease classification changed from moderate-to-severe disease to mild disease. The last patient initially presented with mild disease. Other outcomes noted included improved pruritus in 3 patients and improvement of calcinosis in 1 patient. One patient was additionally able to stop concomitant treatment with prednisone and IVIG at 3 and 6 months, respectively. This patient had been on daily prednisone for 4 years. Only other patient on prednisone was on low dose of 3mg daily. The patients all had normal muscle exams prior to treatment with Tofacitinib. No worsening muscle involvement or adverse effects were noted with Tofacitinib use.Conclusion:Tofacitinib is believed to play a role in the inhibition of IFN signaling pathways that are overactive in dermatomyositis. All four patients within this retrospective study showed significant improvement of cutaneous disease with Tofacitinib use.References:[1]Moghadam-Kia S.Rheumatology. 2019;58(6):1011-1015.[2]Kurtzman D.JAMA Dermatol. 2016;152(8):944.[3]Paik J.Semin Arthritis Rheum. 2017;46(4):e19.[4]Kurasawa K.Rheumatology. 2018;57(12):2114-2119.[5]Anyanwu CO.Br J Dermatol. 2015; 173(4):969-974.Gender/ Age/ EthnicityDM Subtype /disease durationPrevious TreatmentConcomitant Treatment with TOFCDASI ActivityCDASI Activity 3 monthCDASI Activity 6 monthOther OutcomeM/ 55/ CaucasianAmyopathic DM; 5 yearsAZA, HCQ, IVIG, MTX, MMF, Prednisone, RCI, RTX, TACHCQ1254NoneF/ 37/ CaucasianAmyopathic DM; 7 yearsAZA, HCQ, IVIG, MTX, MMF, Prednisone, RCI, TACPrednisone, IVIG, MTX1585Pruritus and CRP improvedF/ 60/ CaucasianAmyopathic DM; 4 yearsAZA, MTX, PrednisonePrednisone, MTX17155Pruritus improvedF/ 47 African AmericanClassic DM; 5 yearsAZA, colchicine, HCQ, IVIG, MTX, MMF, pamidronate Prednisone, RCI, RTX, TACIVIG, Colchicine2287Pruritus and calcinosis improvedAbbreviations: CDASI, Cutaneous Dermatomyositis Disease Area and Severity Index; AZA, azathioprine; CRP, C-reactive protein; DM, Dermatomyositis, HCQ, hydroxychloroquine; IVIG, intravenous immunoglobulin; MTX, methotrexate; MMF, mycophenolate mofetil; RCI, repository-corticotropin injection; RTX, rituximab; TAC, tacrolimus; TOF, tofacitinib;Disclosure of Interests:Kirsten Riggle: None declared, Aarat Patel Speakers bureau: Abbvie, Mallinckrodt, Celgene, Lilly, Rohit Aggarwal Grant/research support from: Pfizer, Genentech, BMS, Mallinckrodt, Consultant of: Pfizer, Genentech, BMS, Mallinckrodt, Bristol Myers-Squibb, octapharma, CSL Behring, AstraZeneca, Corbus, Kezar, Abbvie

Background:Dual-Energy CT (DECT) has high sensitivity and specificity for detecting monosodium urate (MSU) crystal deposition. Although widely used in research, few studies have evaluated the usefulness of DECT in clinical practice.Objectives:To evaluate the use of DECT in a clinical setting and determine its utilityMethods:We retrospectively evaluated the records of all patients referred for DECT scans over a 6.5-year period. Patient charts were reviewed for clinical features.Results:113 patients (17.5/yr) received DECT evaluation at a university hospital over the study period (234 scans). All were referred by rheumatologists. Medical records were available for 69 patients (134 scans), including 44 males and 25 females (mean age 62 (SD, 12.9, range: 34-85 yrs). Mean duration of gout was 6.7 (SD, 8.1) yrs. DECT was ordered to evaluate known gout (36/69, 52.1%), suspected gout (32/69, 46.4%), and suspected calcium pyrophosphate (CPP) disease (1/69, 1.4%). 32/69 (46.4%) of patients were on urate-lowering therapy.61% (42/69) had MSU crystal and none had CPP deposition. Mean MSU volume was 1.6cc (SD, 5.2cc; range: 0.01-35 cc.) The joints imaged were feet/ankles (80/134, 60%) and hands/wrists (53/134, 40%). 23/33 (69.7%) patients with DECT positivity had elevated serum urate (SU) levels >6mg/dL; however, elevated SU was not significantly associated with DECT positivity (odds ratio (OR) 1.9, 95% CI:0.59-5.95, p=0.28).For patients with positive scans, mean gout duration from first known flare was 9.5 (SD, 8.8) yrs.Among patients who had scans completed within 1 yr of the first known gout flare, 1/10 were positive (10%); 4/16 within 2 yrs (25%); and 8/21 within 3 yrs (29.6%).Of patients with positive DECT scans, 24/42 (57%) had symmetric distribution of MSU crystal deposition: 10/24 (42%) hands and 14/24 (58%) feet; with gout duration of 7.9 (SD, 8.0) yrs.Conclusion:DECT was infrequently utilized and only by rheumatologists. Only 60 % of patients referred for DECT scanning because of known or suspected gout had MSU deposition. DECT was uncommonly positive in patients with a 1-3 yr history of gout. When positive, the MSU crystal deposition was symmetrical in most gout patients. DECT scans, while important in furthering our understanding of gout biology, are not routinely used in general practice and often do not provide important decision support information. Establishment of practice guidelines might be important in developing more appropriate utilization of DECT.Disclosure of Interests:Yekaterina Sherman: None declared, Peter Lipsky Consultant of: Horizon Therapeutics, Mark Bramwit: None declared, Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon

Background:Idiopathic Inflammatory Myositis (IIM) are heterogenous, with distinct autoantibodies reflecting upon possible clinical evolution and outcomes. Ethnicity has major influence on both antibody prevalence patterns as well as phenotypic behaviours linked to them.Objectives:Thus we sought prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of patients with IIM.Methods:Adult patients with a physician diagnosis of IIM as per ACR/EULAR classification criteria were investigated for the presence of MSAs/MAAs by Line immunoassay (G4, Euro-Immune, Lubeck, Germany). Anti-Nuclear Antibody (ANA) was tested by Immunofluorescence assay (IFA), and patterns in various antibody subsets explored. Prevalence and associations of different antibodies were assessed in disease subsets and clinical phenotypes.Results:MSA and MAAs were tested in 250 IIM patients (F:M 3.8:1) of median age 37 (25-47) and disease duration 6 (3-17) years. Dermatomyositis (DM) was seen in most patients 83 (33.2%) followed by overlap myositis (OM), juvenile DM, Anti-synthetase syndrome (ASS), polymyositis (PM), and cancer associated myositis (CAM). MSAs/MAAs were found in 148 (59.2%) of patients, of which 95 (64.2%) had an MSA and 53 (35.8%) had MAAs (Fig, 1A). 93 (62.8%) of autoantibody positive patients were positive for a single antibody, and only 2 (0.8%) of total had more than one MSA (Table 1).Table 1.Multiple antibodies positive upon testing for MSA and MAA by the LIANote: ** PL-7 co-exists with Ku + Pm/Scl, **PL-12 co-exists with Pm/Scl + Ro52, **SRP co-exists with Pm/Scl + Ro52The most frequently detected MSA was anti-Jo-1 (8%), with a further 9 specificities each found in 0.5–7.0% of patients. Amongst the autoantibody positive patients, 21% (n=53) had isolated MAA positivity, anti-Ro52 (33, 62.3%) being the most common, followed by anti-Pm/Scl (11, 20.8%) and anti-Ku (9, 17.0%) (Fig. 1B).Figure 1.A. MSA and MAA in Indian cohort of myositis B. ANA patterns in myositis C. MSA in ANA negative IIMOn ANA, 76.0% (172 of 226) were positive, with speckled being the most common pattern (37%,Fig. 1C). Of those ANA negative (n=54), 61% had either MSA or MAA (Fig 1D). 18 (54.6%) had autoantibodies associated with cytoplasmic patterns suggesting that cytoplasmic ANA may be underreported.Clinical presentation akin to DM was seen with all MSA except anti-SRP. PM group was heterogenous, and included ASS, OM and necrotizing phenotype (Fig. 2A). On occasion, anti-SRP, anti-Mi-2 and anti-MDA5 presented with clinical phenotype of ASS. (Fig 2A,C). Patients with ARS or anti-SAE were often clinically amyopathic (Figure 2B,C)Figure 2.A. Phenotypic associated with various antibody subsets B,C,and D. MSA/MAA in muscle weakness, rash and ILD phenotype. E. Unique feature of eye-lid edema in some patients with MDA-5 positive myositisARS were associated with mechanic’s hand (pE) and arthritis in children (p=0.01, OR 11.5). Anti-TIF-1ɣ associated with alopecia (p=0.007,OR 5.9) and malignancy (p= Conclusion:Myositis autoantibodies are seen in two-thirds IIM and identify distinct clinical subsets as well as unique phenotypes. MSA/MAA are positive in two-thirds of those negative on ANA, adding diagnostic value. MSAs are nearly always mutually exclusive and thus useful as biomarkers for diagnosis.Acknowledgments:MSA testing supported by grants from APLAR and Association of Physicians of India.Disclosure of Interests:Latika Gupta: None declared, Priyanka Gaur: None declared, Vikas Agarwal: None declared, Rohit Aggarwal Grant/research support from: Pfizer, Genentech, BMS, Mallinckrodt, Consultant of: Pfizer, Genentech, BMS, Mallinckrodt, Bristol Myers-Squibb, octapharma, CSL Behring, AstraZeneca, Corbus, Kezar, Abbvie, Ramnath Misra: None declared

Background:AWARE (Comparative and Pragmatic Study of Golimumab IV Versus Infliximab in Rheumatoid Arthritis) is an ongoing Phase 4 comparator study designed to provide a real-world assessment of intravenous golimumab (GLM) and intravenous infliximab (IFX) in patients (pts) with rheumatoid arthritis (RA). The study recently reached its primary endpoint (comparison of overall incidence of infusion reactions in GLM- vs IFX-treated pts after 52 weeks) with the last patient reaching 52 weeks of treatment or discontinuation from the study. AWARE also records prior use of biologic medications and concomitant use of methotrexate (MTX).Objectives:To assess the incidence of infusion reactions among GLM and IFX pts reported at baseline by examining the influence of prior biologic exposure or concurrent use of MTX.Methods:AWARE is a prospective, noninterventional, observational, multicenter, 3-year study conducted in the US. RA patients (1,270 adults) were enrolled at the time of initiating treatment with GLM or IFX. All treatment decisions were made at the discretion of the treating rheumatologist. An infusion reaction was any adverse event that occurred during an infusion or within 1 hour after the infusion of either GLM or IFX. Imputations were not performed on these AWARE data. Data shown are mean ± standard deviation.Results:Demographics are shown in Table 1 and the incidence of infusion reactions in different AWARE cohorts is shown in Table 2. GLM and IFX pts were comparable in sex and utilization of MTX at baseline. Both age and disease duration of GLM pts was greater than IFX pts by ~2 years. There was a higher proportion of bionaïve pts in IFX-treated group compared to GLM-treated group. Overall, infusion reactions occurred more frequently among IFX-treated pts compared to GLM-treated pts. The difference in infusion reaction rates between IFX- and GLM-treated pts was also evident among subgroups of bionaïve vs non-bionaïve pts, and among MTX non-users vs MTX users (characteristics reported at baseline). GLM pts did not report any serious or severe infusion reactions. These were reported rarely (3/585 pts) in IFX-treated pts. Among GLM and IFX pts with an infusion reaction, 55.6% of GLM and 77.1% of IFX pts had at least one medication for infusion reaction. Infusion reactions accounted for 9.7% and 35.1% of discontinuations due to adverse events in GLM and IFX pts, respectively.Table 1.Baseline Characteristics in the AWARE StudyGLM (n=685)IFX (n=585)Age (years)60.9 ± 13.4358.0 ± 12.85Sex (% female)85.0 %79.5 %Disease Duration (years)9.16 ± 9.9757.20 ± 9.716Bionaïve (%)33.0%48.6%MTX plus (%)75.4%75.1%MTX=methotrexateTable 2.Infusion Reactions in AWARE in Subsets of Patients ± Prior Biologic Use or ± Concurrent MTXGLM (n=685)IFX (n=585)GLM (n=685)IFX (n=585)BionaïveNon-BionaïveBionaïveNon-BionaïveNo MTX UseMTXUseNo MTX UseMTX UseInfusion Reactions6/242(2.5%)21/443(4.7%)36/251(14.3%)47/334(14.1%)15/265(5.7%)12/420(2.9%)44/229(19.2%)39/356(11.0%)Medication for Infusion Reactions33.3%59.1%78.9%73.6%50.%58.3%73.6%77.6%MTX=methotrexateConclusion:Whether bionaïve, non-bionaïve, MTX non-user or MTX user at baseline, the incidence of infusion reactions was notably lower among GLM- vs IFX-treated pts. Serious and/or severe infusion reactions did not occur among GLM pts and were rare among IFX pts. IFX was more commonly administered mediation for an infusion reaction compared to GLM. Infusion reactions accounted for almost four times the number of discontinuations related to adverse events in IFX pts compared to GLM pts.Disclosure of Interests: :Sergio Schwartzman Grant/research support from: Janssen Research & Development, LLC, Consultant of: AbbVie, Crescendo Bioscience, Dermtech, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceutica, Myriad Genetics, Novartis, Regeneron, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Eli Lilly and Company, Genentech, Janssen Pharmaceutica, Novartis, Pfizer, Regeneron, Sanofi, UCB, Aaron Broadwell Grant/research support from: Janssen Research & Development, LLC, Janssen, Eli Lilly, Consultant of: AbbVie, Amgen, AstraZeneca, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sandoz, Speakers bureau: AbbVie, Amgen, Celgene, GSK, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Radius, Sanofi-Regeneron, UCB, Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Shawn Black Employee of: Janssen Research & Development, LLC, Janssen Scientific Affairs, LLC, Stephen Xu Employee of: Janssen Research & Development, LLC, Wayne Langholff Employee of: Janssen Research & Development, LLC, Shelly Kafka Employee of: Janssen Scientific Affairs, LLC

Background:Intra-articular therapies (IAT) are widely used in clinical practice to treat patients with rheumatic and musculoskeletal diseases (RMDs). Many factors influence their efficacy and safety. There is a wide variation in the way IATs are delivered by health professionals. In an attempt to standardise these procedures, evidence-based recommendations are the right way forward.Objectives:To establish evidence-based recommendations to guide health professionals using IAT in adult patients with peripheral arthropathies.Methods:At a first face-to-face meeting, the results of an overview of systematic reviews were presented to the multidisciplinary task force of members from 8 countries. The aim, scope and outline of the taskforce were also established at this meeting. Thirty-two clinical questions ranked for priority (relevance for practice plus feasibility) drove the systematic reviews performed by two fellows. In addition, two surveys addressed to physicians, health professionals and patients throughout Europe were agreed to acquire more background information. At the second face-to-face meeting, the evidence for each research question was discussed, and each recommendation shaped and voted in a first Delphi round. Level of agreement was numerically scored 0 to 10 (0 completely disagree, 10 completely agree). All panellists voted anonymously using a sli.do app. Agreement needed to be greater than 80% to be included in a second Delphi round, which also allowed reformulation of statements. Finally, a third Delphi round was sent to the taskforce. The level of evidence was assigned to each recommendation according to the EULAR SOP for establishing recommendations.Results:Recommendations focus on practical aspects for daily practice to guide health professionals before, during and after IAT in adult patients with peripheral arthropathies. Five overarching principles were established, together with 11 recommendations that address the following issues: (1) patient information; (2) procedure and setting; (3) accuracy issues; (3) routine and special antiseptic care; (4) safety issues and precautions to be addressed in special populations; (5) efficacy and safety of repeated joint injections; (6) the usage of local anaesthetics; and (7) aftercare. The document includes the supporting evidence and results from the surveys, level of evidence and agreement.Conclusion:We have developed the first evidence and expert opinion based recommendations to guide health professionals using IAT.Acknowledgments:Eular Taskforce grant CL109Disclosure of Interests:Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira: None declared, Terence O’Neill: None declared, Hemant Pandit Grant/research support from: Glaxo Smith Kline (GSK) for work on Diclofenac Gel, Speakers bureau: Bristol Myers Squibb for teaching their employees about hip and knee replacement, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Ingrid Möller: None declared, Valentina Vardanyan: None declared, Jenny de la Torre-Aboki: None declared, Lene Terslev: None declared, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Willm Uwe Kampen: None declared, Elena Nikiphorou: None declared, IRENE Pitsillidou: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Rheumatoid arthritis (RA) has been shown a strong genetic association with particularHLA–DRB1alleles containing shared epitope (SE). However, whether SE is clinically useful in treatment choices is insufficiently investigated1and previous studies have presented mixed findings in the role of SE in the response of TNFi therapies2,3.Objectives:To assess the role of SE in response to TNFi treatment in real-world RA patients (pts).Methods:Pts enrolled in a large RA registry, Brigham and Women’s Hospital RA Sequential Study, with known SE and received TNFi therapies were included for the analysis. TNFi pts were identified by the first-time use of the drugs between March 2003 to June 2018. For this analysis, all pts were followed up to 1 year. Summary statistics are reported for demographics, serostatus and disease activity (DA) at baseline and follow-up, stratified by SE status. Given the strong association of SE and anti-citrullinated protein antibody (ACPA), the analysis was further stratified by ACPA status. The effect of SE on change in DA was assessed using linear regression model with age, gender, RA disease duration, baseline DA, smoking status, SE, ACPA and ACPA-SE interaction as covariates.Results:Of the 484 TNFi pts included in the study, 68.8% were SE+. SE+ pts (vs SE-) were more likely to be rheumatoid factor positive, have erosive disease and a higher disease duration, irrespective of ACPA status. No difference in the change of DA was observed by SE. In SE- pts, ACPA+ pts had a greater reduction of DA than ACPA- pts (Table 1). After accounting for baseline differences, there was no significant effect of SE status on the mean change from baseline in any of the 3 DA measures.(Figure 1) The change in DA was not associated with ACPA but was significantly affected by disease duration and baseline DA.Table 1.Disease Activity in TNFi Patients, Stratified by SE and ACPA StatusParameterSE+ (1 & 2 alleles, n=333)SE- (n=151)ACPA+ACPA–OverallACPA+ACPA-Overall(n=264)(n=69)(n=333)(n=90)(n=61)(n=151)Baseline, Mean (SD)DAS28 CRP3.94 (1.69)3.57 (1.61)3.86 (1.67)3.85 (1.49)3.45 (1.65)3.69 (1.57)CDAI23.06 (18.13)18.95 (15.96)22.25 (17.78)21.91 (15.96)17.72 (17.06)20.26 (16.48)SDAI24.08 (18.82)19.96 (16.59)23.27 (18.45)22.58 (16.34)18.55 (17.87)20.99 (17.01)Follow-up, Mean (SD)DAS28 CRP3.42 (1.55)2.69 (1.32)3.27 (1.53)3.19 (1.43)3.11 (1.53)3.16 (1.47)CDAI17.61 (15.53)12.11 (12.65)16.51 (15.14)15.15 (13.35)14.94 (14.73)15.07 (13.84)SDAI18.35 (15.73)12.45 (12.78)17.15 (15.34)15.31 (13.81)15.71 (15.45)15.46 (14.38)Change, Mean (SD)DAS28 CRP-0.48 (1.31)-0.65 (1.53)-0.52 (1.36)-0.52 (1.50)-0.24 (0.93)-0.42 (1.34)CDAI-4.29 (13.16)-4.79 (13.13)-4.39 (13.12)-6.45 (13.56)-2.63 (9.58)-4.99 (12.28)SDAI-4.74 (14.13)-5.07 (13.90)-4.80 (14.05)-6.87 (14.21)-2.97 (10.32)-5.41 (12.98)Figure 1.Linear Regression Model for Change in Disease Activity*Estimates, p-values are shown as data labels on the graphs; The above model is adjusted for age, gender, RA duration, smoking status, SE status, baseline DA, ACPA and ACPA*SE statusConclusion:This real-world study validates the finding from previous studies conducted in clinical settings that SE does not differentiate treatment response for TNFi therapies.References:[1]Saruhan-Direskeneli G, et al.Rheumatology (Oxford) 2007;46(12):1842-44[2]Skapenko A, et al.Clin Exp Rheumatol2019;37(5):783-790[3]Rigby W, et al.Annals of the Rheumatic Diseases2019;78(2):263-264Disclosure of Interests:Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Joshua Bryson Shareholder of: I own shares of Bristol-Myers Squibb Company, Employee of: I am a paid employee of Bristol-Myers Squibb Company, Qian Xia Shareholder of: I own shares of Bristol-Myers Squibb Company, Employee of: I am a paid employee of Bristol-Myers Squibb Company, Niyati Sharma Consultant of: I work as a consultant for Bristol-Myers Squibb Company, Chidananda Samal Consultant of: I work as a consultant for Bristol-Myers Squibb Company, Sonie Lama Shareholder of: I own shares of Bristol-Myers Squibb Company., Employee of: I am a paid employee of Bristol-Myers Squibb Company., Michael E. Weinblatt Grant/research support from: BMS, Amgen, Lilly, Crescendo and Sonofi-Regeneron, Consultant of: Horizon Therapeutics, Bristol-Myers Squibb, Amgen, Abbvie, Crescendo, Lilly, Pfizer, Roche, Gilead, Nancy Shadick Grant/research support from: Mallinckrodt, BMS, Lilly, Amgen, Crescendo Biosciences, and Sanofi-Regeneron, Consultant of: BMS

Background:Anifrolumab treatment resulted in improved British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA) response rates in patients with systemic lupus erythematosus (SLE) in the phase 3 TULIP-2 and TULIP-1 trials.1,2In addition, annualized flare rates were lower among the groups treated with anifrolumab compared with placebo.1,2Objectives:TULIP-2 and TULIP-1 data were analyzed to assess the effects of anifrolumab on the number of SLE flares and time to first flare during 52 weeks of treatment.Methods:The randomized, double-blind, placebo-controlled TULIP-2 and TULIP-1 trials evaluated efficacy and safety of intravenous anifrolumab 300 mg vs placebo every 4 weeks for 48 weeks, with the primary endpoints assessed at Week 52, in patients with moderate to severe SLE despite standard-of-care treatment. Flares were defined as ≥1 new BILAG-2004 A or ≥2 new (worsening) BILAG-2004 B domain scores compared with the prior month’s visit. Time to first flare was evaluated using a Cox proportional hazards model. Annualized flare rate was analyzed using a negative binomial regression model.Results:In TULIP-2 (anifrolumab, n=180; placebo, n=182) and TULIP-1 (anifrolumab, n=180; placebo, n=184), fewer patients experienced ≥1 BILAG-2004 flare in the anifrolumab groups (TULIP-2: 31.1%, n=56; TULIP-1: 36.1%, n=65) compared with the placebo groups (TULIP-2: 42.3%, n=77; TULIP-1: 43.5%, n=80; Figure 1). Results favoring anifrolumab were observed in time to first flare (TULIP-2: hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.46–0.91 and TULIP-1: HR 0.76, 95% CI 0.55–1.06; Figure 2) and BILAG-based annualized flare rates (TULIP-2: adjusted rate ratio 0.67, 95% CI 0.48–0.94 and TULIP-1: rate ratio 0.83, 95% CI 0.60–1.14) across both trials.Conclusion:Across 2 phase 3 trials, we observed reductions in the total number of flares and annualized flare rates, as well as prolongation of time to first flare with anifrolumab treatment compared with placebo. These results support the potential of anifrolumab to reduce disease activity and reduce flares, benefiting patients with SLE.References:[1]Morand EF, et al.N Engl J Med. 2020;382:211–221.[2]Furie RA, et al.Lancet Rheumatol.2019;1:e208–e219.Disclosure of Interests:Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Eric F. Morand Grant/research support from: AstraZeneca, Consultant of: AstraZeneca, Speakers bureau: AstraZeneca, Anca Askanase Grant/research support from: Regeneron and Pfizer, Consultant of: AbbVie and BMS, Employee of: GSK, AstraZeneca, Janssen, Lilly, and Mallinckrodt, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Rubana Kalyani Employee of: AstraZeneca, Gabriel Abreu Employee of: AstraZeneca, Lilia Pineda Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca

Background:Multimorbidity (≥2 chronic conditions) escalates the risk of adverse health outcomes. However, its burden in people with osteoarthritis (OA) remains largely unknown.Objectives:To identify the clusters of patients with multimorbidity and associated factors in OA and non-OA populations and to estimate the risk of developing multimorbidity clusters after the index date (after diagnosis).Methods:The study used the Clinical Practice Research Datalink – a primary care database from the UK. Firstly, age, sex and practice matched OA and non-OA people aged 20+ were identified to explore patterns and associations of clusters of multimorbidity within each group. Non-OA controls were assigned with same index date as that of matched OA cases. Secondly, multimorbidity trajectories for 20 years after the index date were examined in people without any comorbidities at baseline in both OA and non-OA groups. Latent class analysis was used to identify clusters and latent class growth modelling was used for cluster trajectories. The associations between clusters and age, sex, body mass index (BMI), alcohol use, smoking habits at baseline were quantified through multinomial logistic regression.Results:In total, 47 long-term conditions were studied in 443,822 people (OA- 221922; non-OA- 221900), with a mean age of 62 years (standard deviation ± 13 years), and 58% being women. The prevalence of multimorbidity was 76.6% and 68.9% in the OA and non-OA groups, respectively. In the OA group five clusters were identified including relatively healthy (18%), ‘cardiovascular (CVD) and musculoskeletal (MSK)’ (12.3%), metabolic syndrome (28.2%), ‘pain and psychological (9.1%), and ‘musculoskeletal’ (32.4%). The non-OA group had similar patterns except that the ‘pain+ psychological’ cluster was replaced by ‘thyroid and psychological’. (Figure 1) Among people with OA, ‘CVD+MSK’ and metabolic syndrome clusters were strongly associated with obesity with a relative risk ratio (RRR) of 2.04 (95% CI 1.95-2.13) and 2.10 (95% CI 2.03-2.17), respectively. Women had four times higher risk of being in the ‘pain+ psychological’ cluster than men when compared to the gender ratio in the healthy cluster, (RRR 4.28; 95% CI 4.09-4.48). In the non-OA group, obesity was significantly associated with all the clusters.Figure 1: Posterior probability distribution of chronic conditions across the clusters in Osteoarthritis (OA, n=221922) and Non-Osteoarthritis (Non-OA, n=221900) group. COPD- Chronic Obstructive Pulmonary Disease; CVD- Cardiovascular; MSK- MusculoskeletalOA (n=24139) and non-OA (n=24144) groups had five and four multimorbidity trajectory clusters, respectively. Among the OA population, 2.7% had rapid onset of multimorbidity, 9.5% had gradual onset and 11.6% had slow onset, whereas among the non-OA population, there was no rapid onset cluster, 4.6% had gradual onset and 14.3% had slow onset of multimorbidity. (Figure 2)Figure 2: Clusters of multimorbidity trajectories after index date in OA (n=24139) and Non-OA (n=24144)Conclusion:Distinct identified groups in OA and non-OA suggests further research for possible biological linkage within each cluster. The rapid onset of multimorbidity in OA should be considered for chronic disease management.Supported by:Acknowledgments:We would like to thank the University of Nottingham, UK, Beijing Joint Care Foundation, China and Foundation for Research in Rheumatology (FOREUM) for supporting the study.Disclosure of Interests:Subhashisa Swain: None declared, Carol Coupland: None declared, Victoria Strauss: None declared, Christian Mallen Grant/research support from: My department has received financial grants from BMS for a cardiology trial., Chang-Fu Kuo: None declared, Aliya Sarmanova: None declared, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Weiya Zhang Consultant of: Grunenthal for advice on gout management, Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium

Background:The use of a specific and widely used type of intravenous ferrotherapy, ferric carboxymaltose (FCM), has been linked to the development of an asymptomatic and transient hypophosphataemia. However, in recent years it has been published that it can generate a severe hypophosphataemic osteomalacia (HPO) mediated by fibroblast growth factor 23 (FGF23) that is associated with high morbidity1. It is a potentially serious adverse effect whose prevalence is unknown and that clinicians may know little about.Objectives:To know the clinical and biochemical characteristics of this adverse effect and make it visible in the medical community.Methods:Observational descriptive study of three cases of patients assessed in the Rheumatology department of our hospital who were referred for study of recurrent fractures and diagnosed of FGF23-mediated HPO due to FCM. Demographic, clinical and laboratory data of the patients are described.Results:The clinical and laboratory characteristics of the patients are shown in table 1. All patients presented clinical and biochemical features compatible with FGF23-mediated HPO (mean of FGF levels 240 kRU/L, NR 0-145). All had multiple insufficiency fractures (Fx) and/or avascular necrosis (AN), with hip involvement in all 3 cases. Other causes of HPO were ruled out in all of them using PET18F-FDG, octreotide scintigraphy, abdominal magnetic resonance and PET68Ga-DOTATOC, and a genetic study of hypophosphataemic rickets was also performed in case 1. In all patients FCM was discontinued and phosphate levels were progressively normalized allowing the withdrawal of oral phosphate and calcitriol replacement therapy. After metabolic normalization, none presented new Fx or AN.Table 1.Clinical and biochemical characteristics of the patientsCase 1Case 2Case 3Age (years)a367543Medical historyCrohn’s disease (CD), right hemicolectomy. CD-associated spondyloarthritisSmall bowel angiodysplasiasAntisintetase syndrome. Uterine fibroids.Cause of anemiaGastrointestinal bleeding and malabsorptionGastrointestinal bleedingGynecological bleedingFe-CBX start date10/201008/201302/2018Fe-CBX discontinuation date10/201811/201806/2018Total time Fe-CBX (months)96634FracturesAN: left calcaneus posterior tuberosity, astragaline dome, right femoral headFx: left talus, tibial pylon, tibia-astragaline and ischiopubial branch; right 2nd metatarsal, distal tibia, posterior tuberosity of calcaneusFx both femoral necks and right sacral wingAN both femoral headsBone densitometryLS: Z-score-2.4FN: Z-score -2.4LS: Z-score -0.5FN: Z-score -1.3Phosphate, mg/dL (NR 2.5-4.5)a1.81.61.3Calcium, mg/dL (NR 8.6-10.2)a9.18.39.01,25(OH)zD3, ng/ml (NR 30-100)a54127PTH, pg/ml (NR 12-65)a71223104AP, UI/L (NR 46-116)a11314086Ph-exc, mg/24h (NR 400-1300)a16091630489TPR, % (NR 73-87)a58.350.270.7FGF-23, kRU/L (NR 0-145)a183335201Time to normalizationb1048aDuring treatment with FCM.bOf serum phosphate levels since FCM discontinuation in months. LS: Lumbar spine. FN: Femoral neck. NR: Normality range..PTH: Parathyroid hormone. AP: Alkaline phosphatase. Ph-exc: 24-hour urine phosphate excretion. Ph-cl: phosphate clearance. TPR: Tubular phosphate reabsorption. Data highlighted in bold indicate altered values.Conclusion:Treatment with FCM can cause severe FGF23-mediated HPO, multiple fractures and a great decrease in the quality of life. Since it can be potentially serious and easily reversible, it is important to favor the dissemination of these new cases and the knowledge of this disease. The need to monitor phosphate and/or FGF23 levels in patients receiving this intravenous iron therapy should be evaluated.References:[1]Bishay RH, Ganda K, Seibel MJ. Long-term iron polymaltose infusions associated with hypophosphataemic osteomalacia: a report of two cases and review of the literature. Ther Adv Endocrinol Metab. 2017;8(1-2):14–19. doi:10.1177/2042018816678363Disclosure of Interests:Elisa Fernández: None declared, Carolina Tornero: None declared, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB, Gemma Bonilla: None declared, Chamaida Plasencia: None declared, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz, Pilar Aguado: None declared

Background:Intra-articular therapies (IAT) are routinely used in rheumatic and musculoskeletal diseases (RMDs); however large variability exists regarding current practice of delivery amongst health professionals.Objectives:To inquire about common practice aspects to inform the EULAR Taskforce for the IAT of arthropathies.Methods:A steering committee prepared a 160-item questionnaire based on the information needs of the Taskforce. The survey was disseminated via EULAR professional associations and social media and it was open to any health professional treating persons with RMDs, regardless of using IAT personally.Results:The survey was answered by 186 health professionals from 26 countries, the large majority of whom (77%) were rheumatologists, followed by nurses (12%), general practitioners (2%) and orthopaedic surgeons (2%). The two collectives that perform IAT routinely are rheumatologists (97%) and orthopaedic surgeons (89%), with other professionals Conclusion:Although often performed in clinical practice for RMDs, there is apparent variability in several elements related to delivery of this treatment. This information, together with patient input, will help design current recommendations where research evidence is not available.Acknowledgments:Eular Taskforce grant CL109Disclosure of Interests:Jenny de la Torre-Aboki: None declared, IRENE Pitsillidou: None declared, Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Lene Terslev: None declared, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Hemant Pandit Grant/research support from: Glaxo Smith Kline (GSK) for work on Diclofenac Gel, Speakers bureau: Bristol Myers Squibb for teaching their employees about hip and knee replacement, Ingrid Möller: None declared, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Willm Uwe Kampen: None declared, Terence O’Neill: None declared, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Valentina Vardanyan: None declared, Elena Nikiphorou: None declared, Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)