SAT0432 EFFECT OF SEX ON DISEASE CHARACTERISTICS AND DISEASE IMPACT IN PATIENTS WITH PSORIATIC ARTHRITIS (PsA): INSIGHTS FROM THE REAL-WORLD, OBSERVATIONAL MULTINATIONAL PsABio COHORT

Background:Female sex has been associated with more severe disease and poorer treatment outcomes in PsA. These observations are often based on small populations or national cohorts/registries.Objectives:To investigate the effects of sex on disease characteristics and disease impact in PsA, using data of 929 consecutive patients (pts) from PsABio.Methods:PsABio is a real-world, non-interventional European study in PsA pts treated with UST or TNFi based on their rheumatologist's choice. Observed male and female baseline (BL) data were described and compared using 95% CI.Results:Women in PsABio (n=512 [55%]) were numerically older than men (mean [SD]: 50.5 [12.7] / 48.7 [12.3] years, respectively). Women were more obese (BMI >30), % (95% CI): F: 35 (30, 39), M: 24 (20, 29), men more overweight (BMI >25–30): F: 31 (27, 36), M:51 (46, 57). Age at diagnosis, delay from first symptom to diagnosis, and disease duration were similar for both sexes.Women entered PsABio more often on 3rd line treatment, whereas men started on 1st-line biologic treatment more often (F/M 1st line 47%/55%; 2nd line 34%/33%; 3rd line 20%/12%). Numerically, concomitant MTX was given more often to women vs men (32% vs 27%). At BL, 60% of women and 64% of men were on NSAIDs; 7.9% and 2.5% on antidepressant drugs. Women had significantly more comorbidities, with numerically more cardiovascular disease and anxiety/depression, and 3 times more IBD.Women had significantly higher 68 tender joint counts (TJC): 13.0 vs 10.4, while 66 swollen joint counts were not significantly different: 5.8 vs 5.5. Axial or combined axial-peripheral disease was similarly frequent, in 29% of women and 26% of men (Figs. 1, 2).Clinical Disease Activity index for PSoriatic Arthritis (cDAPSA) was higher in women (31.8 vs 27.3); pt-reported levels of pain, global disease activity (VAS scales) and higher TJC contributed to this. While enthesitis prevalence (based on Leeds Enthesitis Index) was comparable, men had significantly more frequent dactylitis, nail disease and worse skin psoriasis. At BL, 3.4% of women vs 7.1% of men, were in MDA.Regarding physical functioning (HAQ-DI), impact of disease (PSAID-12) and quality of life (EQ5D-3L health state), women with PsA starting a biologic (b)DMARD, expressed significantly greater negative impact and more limitations due to their disease (Fig. 2).Conclusion:In routine care, women with PsA starting a bDMARD presented with worse outcomes over a range of assessments compared with men (higher pt-reported pain and disease activity, TJC, and worse physical functioning and QoL), while men had worse dactylitis and psoriasis. Follow-up analysis will report whether the effects of biologic therapy are different in both sexes. The increased prevalence of associated features related to pain and impact on functioning and QoL may indicate the need for a more comprehensive treatment approach for women to avoid unnecessary and premature bDMARD stop or switch.Acknowledgments:This study was funded by Janssen.Disclosure of Interests:Michael T Nurmohamed Grant/research support from: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Consultant of: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Speakers bureau: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Arno WR van Kuijk Grant/research support from: Janssen, Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Consultant of: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – consultant, Speakers bureau: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – speakers bureau and honoraria, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Wim Noel Employee of: Janssen Pharmaceuticals NV, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UC

Increased expression of carbonic anhydrase I in the synovium of patients with ankylosing spondylitis

<p>Abstract</p> <p>Background</p> <p>One of the most distinctive features of ankylosing spondylitis (AS) is new bone formation and bone resorption at sites of chronic inflammation. Previous studies have indicated that the hyperplasia and inflammation of synovial tissues are significantly related to the pathogenic process of AS. The present study used a proteomic approach to identify novel AS-specific proteins by simultaneously comparing the expression profiles of synovial membranes from patients with AS, rheumatoid arthritis (RA) and osteoarthritis (OA).</p> <p>Methods</p> <p>Synovial tissues were collected from the hip joints of patients with AS and knee joints of patients with RA or OA (n = 10 for each disease) during joint replacement surgery. Proteins extracted from the synovial tissues were separated by 2-D electrophoresis (2-DE), and the proteins with significantly increased expression in the AS samples were subjected to MALDI-TOF/TOF-MS analysis. The results were verified using western blotting and immunohistochemistry. Levels of the candidate proteins in synovial fluids from knee joints (n = 40 for each disease) were measured using ELISA.</p> <p>Results</p> <p>The proteomic approach revealed significantly increased expression of carbonic anhydrase I (CA1) in the synovial membrane of patients with AS as compared with the RA and OA tissue samples. Immunohistochemistry and western blotting analysis confirmed the findings described above. The ELISA detected a higher level of CA1 in synovial fluids from patients with AS than those with OA. The mean value of the CA1 level was also higher in AS patients as compared with RA patients. This study also detected increased expression of alpha-1-antitrypsin in the synovial tissues from AS patients, which is in agreement with other reports.</p> <p>Conclusion</p> <p><it>In vitro </it>experiments by other groups indicated that CA1 catalyzes the generation of HCO₃^-through the hydration of CO₂, which then combines with Ca²⁺to form a CaCO3 precipitate. Calcification is an essential step of bone formation. Substantial evidence indicates that carbonic anhydrase also stimulates bone resorption. Hence, overexpression of CA1 in the synovial tissues of AS patients may promote improper calcification and bone resorption in AS.</p

Evidence for Significant Overlap between Common Risk Variants for Crohn's Disease and Ankylosing Spondylitis

BACKGROUND: A multicenter genome-wide association scan for Crohn's Disease (CD) has recently reported 40 CD susceptibility loci, including 29 novel ones (19 significant and 10 putative). To gain insight into the genetic overlap between CD and ankylosing spondylitis (AS), these markers were tested for association in AS patients. PRINCIPAL FINDINGS: Two previously established associations, namely with the MHC and IL23R loci, were confirmed. In addition, rs2872507, which maps to a locus associated with asthma and influences the expression of the ORMDL3 gene in lymphoblastoid cells, showed a significant association with AS (p = 0.03). In gut biopsies of AS and CD patients, ORMDL3 expression was not significantly different from controls and no correlation was found with the rs2872507 genotype (Spearman's rho: -0.067). The distribution of p-values for the remaining 36 SNPs was significantly skewed towards low p-values unless the top 5 ranked SNPs (ORMDL3, NKX2-3, PTPN2, ICOSLG and MST1) were excluded from the analysis. CONCLUSIONS: Association analysis using risk variants for CD led to the identification of a new risk variant associated with AS (ORMDL3), underscoring a role for ER stress in AS. In addition, two known and five potentially relevant associations were detected, contributing to common susceptibility of CD and AS

A Functional Variant in ERAP1 Predisposes to Multiple Sclerosis

The ERAP1 gene encodes an aminopeptidase involved in antigen processing. A functional polymorphism in the gene (rs30187, Arg528Lys) associates with susceptibility to ankylosying spondylitis (AS), whereas a SNP in the interacting ERAP2 gene increases susceptibility to another inflammatory autoimmune disorder, Crohn's disease (CD). We analysed rs30187 in 572 Italian patients with CD and in 517 subjects suffering from multiple sclerosis (MS); for each cohort, an independent sex- and age-matched control group was genotyped. The frequency of the 528Arg allele was significantly higher in both disease cohorts compared to the respective control population (for CD, OR = 1.20 95%CI: 1.01–1.43, p = 0.036; for RRMS, OR = 1.26; 95%CI: 1.04–1.51, p = 0.01). Meta-analysis with the Wellcome Trust Cases Control Consortium GWAS data confirmed the association with MS (pmeta = 0.005), but not with CD. In AS, the rs30187 variant has a predisposing effect only in an HLA-B27 allelic background. It remains to be evaluated whether interaction between ERAP1 and distinct HLA class I alleles also affects the predisposition to MS, and explains the failure to provide definitive evidence for a role of rs30187 in CD. Results herein support the emerging concept that a subset of master-regulatory genes underlay the pathogenesis of autoimmunity

Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force

Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field