ABSTRACTS - Wiley Online Library

bs_bs_banner

Abstracts

ABSTRACTS ARA Oral Abstracts ARA1 EXOMEWIDE ASSOCIATION STUDY OF ANKYLOSING SPONDYLITIS IDENTIFIES ADDITIONAL CODING REGION GENETIC ASSOCIATIONS WITH AS AND STRENGTHENS EVIDENCE OF SHARED GENETIC BACKGROUND WITH INFLAMMATORY BOWEL DISEASE Robinson P1, Leo P2, Pointon J3, Harris J4, Cremin K4, Bradbury L4, Stebbings S5, Harrison A6, Duncan E4, Wordsworth P3, Brown M4 1

Centre for Neurogenetics and Statistical Genomics, Queensland Brain Institute, University of Queensland 2 University of Queensland Diamantina Insititute, University of Queensland, Brisbane, Australia 3 National Institute for Health Research (NIHR) Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre, Headington, Oxford, UK 4 University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia 5 University of Otago, Dunedin, New Zealand 6 University of Otago, Wellington, New Zealand Aim: Ankylosing spondylitis is a common chronic immune-mediated arthropathy affecting primarily joints of the spine and pelvis. The condition is strongly associated with HLA-B27, and association with other HLA variants has been demonstrated. In addition to these effects, to date 30 nonMHC loci have been associated with the disease, and significant additional heritability remains. Methods: To identify further genetic variants associated with the disease, we undertook a study of ankylosing spondylitis using 5,040 patients and 21,133 healthy controls using the Illumina Exomechip microarray. This assays all coding variation in the genome along with genomewide association hits and major histocompatibility tag single nucleotide polymorphisms. Analysis was carried out with logistic regression using principal component analysis to correct for any population stratification.

Results: Novel associations achieving genomewide significance were found in USP8 (P = 3.5 × 10–52, OR = 1.97) and CDKAL1 (P = 1.8 × 10-8, OR = 1.18). Suggestive associations with common variants in FAM118A (P = 5.9 × 10-8, OR = 1.16), C7orf72 (P = 1.9 × 10-7, OR = 1.14) and FAM114A1 (P = 1.4 × 10-6, OR = 1.14) were also found. A low frequency SNP was associated (MAF cases/controls: 0.0044/0.0017) in patatin-like phospholipase domain containing 1 (PNPLA1) at a suggestive level of significance (P = 1.5 × 10-6, OR = 2.6). Conclusions:This study describes novel genetic associations with ankylosing spondylitis. Three of the variants have been previously associated with inflammatory bowel disease (IBD), and one variant with low hip bone mineral density.These findings further increase the evidence for the marked similarity of genetic risk factors for IBD and AS, consistent with the two diseases having very similar aetiopathogenesis. ARA2 A NOVEL MONOCYTE-SPECIFIC NON-CODING RNA UNDERLIES THE CHROMOSOME 21Q22 INTERGENIC GENETIC ASSOCIATION IN ANKYLOSING SPONDYLITIS Haynes K, Kenna T, Glazov E, Brown M, Thomas G The University of Queensland Diamantina Institute, Queensland Aim: Of the 43 independent genetic associations that have been reported for ankylosing spondylitis, most occur in intergenic, intronic or other untranslated regions of the genome. One in particular, at chromosome 21q22, occurs in a gene desert region with no annotated genes.

Results: We identified two completely novel divergently transcribed long non-coding RNAs (lncRNA) expressed from this region, which were upregulated in AS cases compared with healthy controls, as well as those subjects carrying the susceptibility allele. This overexpression in PBMCs was confirmed in two independent data sets, using both conventional RNAseq and qPCR. To further elucidate the potential function of this novel transcript we mined the Fantom5 Atlas of human gene expression which showed expression of the 21q22 transcripts in CD14+ monocytes. We confirmed this in purified CD14+ cells from our PBMC samples with no expression seen in any other cell type. Expression was also significantly enhanced by stimulation of the monocytes with microbial components. Conclusions: This is the first example of a role for a lncRNA in AS and strongly supports a role for monocytes in AS aetiology possibly through responses to microbes. Monocyte antigen presentation has previously been implicated in AS strengthened by the identification of the HLA-B27ERAP1 genetic interaction. Aberrant microbial-induced CD14+ monocyte expression of the 21q22 transcript presents a novel potential mechanism by which AS might be influenced by microbes. ARA3 INFLAMMASOME ACTIVATION IN SALIVARY GLAND EPITHELIAL CELLS – A DISEASE MODEL FOR PRIMARY SJÖGREN ‘S SYNDROME Lau A1, Bosco M2, Lester S2, Roscioli E3, Zalewski P3, Rischmueller M2 1

The University of Adelaide Rheumatology Department, the Queen Elizabeth Hospital Department of Medicine, the Queen Elizabeth Hospital, South Australia

2 3

Aim: Primary Sjögren’s Syndrome (pSS) is an autoimmune inflammatory disease affecting salivary glandular epithelium. It is characterised by the presence of immune complexes comprising autoantibodies bound to RNA/ protein, which correlate with disease severity and potentially drive inflammation. Inflammasomes are a component of the innate immune system thought to play a role in immune surveillance of mucosal surfaces. We hypothesise that inflammasome activation by immune complexes may play a key role in salivary gland inflammation in pSS. In immune cells, inflammasome activation requires both priming through toll-like receptors (eg LPS-TLR4 for NLRP3), followed by specific activation. However, nothing is known about inflammasome priming in salivary gland epithelial cells (SGEC). The aim of this study was to examine TLR priming, of both NLRP3 and AIM2 inflammasomes in a human, secondary SGEC line. Methods: A253 cells were primed with PolyIC (TLR 3), LPS (TLR4), Imiquimod (TLR 7) and CL264 (TLR 7) for 6 hours. Changes in transcript/ protein levels were measured by both qPCR, western blotting and immunocytochemistry. Results: NLRP3 was lowly expressed, by both qPCR and western blot, and was not induced by any TLR ligands. However, polyIC upregulated both AIM2 and IL-1beta as shown by both qPCR (6-fold and 3-fold respectively, p < 0.05) and western blot. Preliminary immunohistochemistry demonstrates AIM2 staining of the epithelium lining the ducts and acini of salivary gland biopsies from both pSS patients and controls. Conclusions: The AIM2 inflammasome is expressed in SGEC lining the ducts and acini, and polyIC, a dsRNA analogue, primes the AIM2 inflammasome in the A253 SGEC cell line. These results support a potential role for inflammasome activation in SGEC in pSS, possibly mediated by RNA containing immune complexes which are present in this disease. The A253 SGEC cell line may be a suitable model to further investigate inflammasome activation by immune complexes in epithelial cells.

Methods: We have used a new technique known as CaptureSeq, which utilises RNAseq on samples enriched for transcripts from a genomic region of interest allowing the detection of very rare or highly cell-specific transcripts expressed at too low levels for detection by conventional RNAseq. Using this technique, we undertook ultra-deep transcriptional profiling in peripheral blood mononuclear cells from 5 cases carrying the protective allele and 5 carrying the susceptibility allele at the 21q22 gene desert locus.

© 2015 The Authors Internal Medicine Journal © 2015 Royal Australasian College of Physicians Internal Medicine Journal (2015) 45 (Suppl. 2): 1–46

1

Abstracts

ARA4 NEUTROPHIL EXTRACELLULAR TRAPS (NETS) ARE PRESENT IN THE JOINT FLUID OF INFLAMMATORY ARTHRITIS PATIENTS Chatfield S1, Grebe K1, McKenzie B2, Wicks I1 1 2

Walter and Eliza Hall Institute of Medical Research CSL Ltd, Victoria

ARA6 SINGLE NUCLEOTIDE POLYMORPHISMS IN THE PROTEIN TYROSINE PHOSPHATASE (PTPN22) GENE ARE ASSOCIATED WITH SUSCEPTIBILITY TO IDIOPATHIC INFLAMMATORY MYOSITIS Maundrell A1, Wiese M2, Lester S3, Rischmueller M4, Cleland L1, Blumbergs P5, Limaye V1 1

Aim: Neutrophil Extracellular Traps (NETs) are structures released by activated neutrophils, comprising neutrophil-derived DNA bound to neutrophil proteins, such as myeloperoxidase (MPO). Stimuli such as urate crystals and rheumatoid arthritis (RA)-associated autoantibodies can trigger NET release in vitro. Markers of NET formation could be clinically useful. This study measures MPO-DNA complexes ex vivo in the synovial fluid (SF) and serum of patients with various types of arthritis. Methods: Synovial fluid (SF) was aspirated from patients with inflammatory arthritis (IA): RA (n = 24); spondyloarthritis (SpA, n = 15) and; crystal arthritis (CA, n = 13) and degenerative osteoarthritis (OA, n = 10). Serum was taken from a subset of patients and from healthy controls.We developed a novel antibody capture and DNA fluorescence assay to measure MPODNA complexes in cell-free supernatant, with results expressed as arbitrary fluorescence units (AFU). Results: Patients with IA had higher levels of MPO-DNA complexes (reflecting NET formation), than patients with OA. The levels of MPODNA in the IA samples were similar: RA 24,169 median AFU, SpA 8,331 AFU, CA 26,628 AFU, OA 436 AFU (p < 0.01 for each, compared individually to OA). SF MPO-DNA correlated with SF white cell counts in RA and CA synovial fluids, but not in SpA SF. In contrast, MPO-DNA levels were not elevated in the majority of serum samples. Conclusions: MPO-DNA is found in the SF but not the serum of patients with inflammatory arthritis, and levels are higher than in non-inflammatory OA SF. These findings suggest that under inflammatory conditions, NETs form in the articular space, leading to high local extracellular DNA concentrations. The physiological implications of this finding are being currently explored. ARA5 DEFICIENCY OF GILZ CHARACTERIZES ACTIVE SLE Morand E, Toh A, Harris J, Jones S Monash University, Victoria Aim: Glucocorticoids (GC) are used in >70% of patients with SLE. GILZ has emerged as a major anti-inflammatory mediator of GC actions, but its role in SLE is unknown. We tested the hypothesis that GILZ is deficient in SLE. Methods: Intracellular GILZ was measured in PBMC obtained from consenting controls (n = 17) and SLE patients (ACR 4 or more, n = 31) in a single centre cohort, by multicolour FACS. Disease activity was measured using SLEDAI2k. Public domain mRNA expression databases were mined.

Royal Adelaide Hospital University of South Australia 3 The Queen Elizabeth Hospital 4 The Queen Elizabeth Hospital, the University of Adelaide 5 SA Pathology, the University of Adelaide, South Australia 2

Aim: A single nucleotide polymorphism (SNP) (1858Cïƒ T, R620W) in the protein tyrosine phosphatase N22 (PTPN22) gene confers susceptibility to autoimmune diseases including rheumatoid arthritis and has been shown to be associated with susceptibility to idiopathic inflammatory myositis (IIM) in a UK-based population.This aim of this study was to determine whether R620W confers susceptibility to IIM in South Australian (SA) patients with IIM. Methods: Genotyping for the PTPN22 SNPs was performed on stored DNA from 199 patients with histologically-confirmed polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) and compared with 241 Caucasian local population controls. The control group conformed to Harvey-Weinberg equilibrium and allele frequencies were comparable to a control cohort from a published meta-analysis (1). Within the IIM population, associations with myositis-specific (MSA) and myositisassociated (MAA) autoantibodies were investigated. Typing for HLA Class I (serology) and Class II (allele level) has been previously performed on many patients with IIM and possible associations of the 8.1 ancestral haplotype (AH) and PTPN22 mutations were investigated. Results: The PTPN22 R620W minor allele frequency was increased in IIM patients (50/398, 12.6%) compared to controls (36/482, 7.5%), OR 1.74 (1.12–2.72), p = 0.015. The results for the disease subgroups were as follows: DM [n = 24, OR 0.83 (0.24–2.79), p = 0.76], PM [n = 75, OR 1.95 (1.09–3.49), p = 0.02] and IBM [n = 61, OR 1.77 (0.93–3.35), p = 0.07]. Within IIM patients, there was no association between the R620W minor allele and detection of any MSA/MAA [OR 0.76 (0.31–1.83), p = 0.54] nor HLA-DR1*03 A1B8 [OR 1.9 (0.84–4.4), p = 0.13]. Conclusions: The PTPN22 R620W minor allele is associated with susceptibility to IIM in South Australian patients, in particular in those with PM and IBM.This association appears to be independent of the known risk for disease conferred by the 8.1 AH. REFERENCE 1. Song GG et al. The PTPN22 C1858T polymorphism and rheumatoid arthritis: a meta-analysis. Rheumatol Int. 2013;33(8):1991–9)

Results: Using several public databases, we observed reduced GILZ mRNA expression in SLE PB B cells, and in renal biopsies of patients with active nephritis, as well as a negative association of GC-adjusted GILZ with disease activity. We therefore next studied GILZ expression in SLE patient leukocytes subsets in detail. SLE patients were 40 (23–66) years old, 90% female, had median ACR criteria of 5 (4–9) and active disease (median SLEDAI-2k = 6 (0–22)). 71% were taking prednisolone. GILZ was readily detected in PBMC and subsets. Significant differences in GILZ expression were observed, with highest expression in myeloid cells than B and T cell subsets. Moreover, GILZ was significantly lower in pDC than monocytes (p < 0.001), and in post-switch than in pre-switch memory B cells (p < 0.01). GILZ expression was higher in patients taking GC (prednisolone) across multiple subsets. However, intracellular GILZ normalized to prednisolone dose exhibited highly significant negative correlation with disease activity (SLEDAI-2k) in total PBMC and in subsets including pDC, monocytes, mature naïve B cells, HLADRLo plasmablasts, and CD4 and CD8 T cell subsets. Conclusions: These data indicate a strong association between reduced GILZ and the presence of SLE, as well as active disease among SLE patients. These findings add to evidence of GILZ as a potential therapeutic target in SLE.

2


Abstracts

ARA7 TARGETED PLASMACYTOID DENDRITIC CELL (pDC) DEPLETION WITH AN ANTI-CD123 mAb (CSL362) – A POTENTIAL NOVEL TREATMENT FOR SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Oon S1, Wilson N2, Wicks I1 1

The Walter and Eliza Hall Institute, the Royal Melbourne Hospital, the University of Melbourne 2 CSL Limited, the University of Melbourne, Victoria Aim: pDCs produce IFNα, a key pathogenic cytokine in SLE. CSL362, a novel anti-CD123 mAb, effects antibody-dependent cell-mediated cytotoxicity (ADCC) against CD123-expressing cells and neutralizes IL-3 signaling. This study of SLE and healthy donors evaluates 1) CD123 expression on pDCs and other cells, 2) CSL362-mediated pDC depletion, and 3) the effect of CSL362 on IFNα production and IFNα-inducible gene expression from peripheral blood mononuclear cells (PBMCs) in vitro. Methods: CD123 expression was assessed by quantitative flow cytometry using Quantibrite-PE beads (n = 50). The percentage of viable pDCs after 24 hour incubation of PBMCs with CSL362, the Fab portion of CSL362 (which only neutralizes IL-3 signaling), or isotype control was determined by flow cytometry (n = 44). IFNα production was measured by ELISA after stimulating PBMCs with TLR9 agonist (CpG) for 18 hours, following pre-treatment with CSL362, Fab or isotype control for 24 hours (n = 20). A novel ‘IFN gene score’, comprising 11 IFNα-inducible genes, was developed to serve as a targeted ‘gene signature’. This score was validated by quantitative PCR on whole blood RNA, by comparing the average of the log2 fold change for the 11 genes between SLE and healthy donors (n = 50). This score was also evaluated by quantitative PCR on PBMCs stimulated with CpG, following CSL362 or isotype control pre-treatment (n = 12). Results: In peripheral blood, pDCs most highly expressed CD123. CSL362 potently depleted pDCs (15.8 ± 3.1% [mean ± SEM], p < 0.0001) and inhibited CpG-induced IFNα production (0.8 ± 0.6%, p < 0.0001) compared to isotype control; effects not observed with Fab.The IFN gene score was elevated in SLE (3.0 ± 0.4) compared to healthy (0.4 ± 0.3, p < 0.0001) donors. CpG-induced upregulation of the score (4.7 ± 0.7) was reduced by CSL362 pretreatment (1.3 ± 0.6, p = 0.001). Conclusions: CSL362 potently depletes pDCs and decreases CpGinduced IFNα production and IFNα-inducible gene expression in vitro in SLE and healthy donors. Cytoreductive therapy with CSL362 may therefore represent a novel treatment strategy in SLE. ARA8 COMPARATIVE RE-FRACTURE RATES IN HOSPITALS WITH AND WITHOUT A FRACTURE LIAISON SERVICE: A 6 MONTH HISTORICAL COHORT STUDY Nakayama A, Major G, Bogduk N

Conclusions: During the study period there were ∼30% reduction in any re-fractures and ∼40% reduction in major re-fractures at John Hunter Hospital compared with another tertiary hospital without a fracture liaison service. ARA9 INTERLEUKIN-23 MEDIATES PSORIASIS-LIKE INFLAMMATION IN THE SKG MOUSE MODEL OF SPONDYLOARTHROPATHY Benham H1, Rehaume L1, Baillet A1, Bhuyan Z1, Bowman J1, Pang D1, Kikly K2, Strutton G3, Ranjeny T1 1

University of Queensland Diamantina Institute Biotechnology Discovery Research, Eli Lilly and Co 3 Department of Pathology Princess Alexandra Hospital, Queensland 2

Aim: Psoriasis (Ps) is a common immune-mediated inflammatory skin disease and is a well recognised extra-articular manifestation of the spondyloathopathies (SpA). Genetic studies implicate IL-23 signalling in the pathogenesis of both Ps and SpA. Spondyloarthritis and psoriasis-like disease develop in an IL-23-dependent fashion in ZAP70-mutant SKG mice.We characterised curdlan (1,3-D-Bglucan) induced psoriasis-like inflammation in the SKG mouse model of SpA, investigating the role of IL-23, IL-22/IL-17, regulatory T cells and microbiota. Methods: SKG, IL-17A-deficient SKG, Germ Free SKG and Foxp3-DTR SKG mice were injected intraperitoneally with curdlan to induce disease. Anti-mouse IL-22, anti-IL-23 or isotype antibodies were given i.p one day before curdlan, and weekly until sacrifice. Recombinant IL-23 or PBS was administered intra-dermally into ear skin. Outcomes were measured by clinical and histological scoring; cytokines by qRT-PCR and in supernatants of tissue explants by ELISA/CBA and cell phenotype from skin-draining lymph nodes by flow cytometry. Results: Curdlan induced ps-like inflammation in addition to SpA in 100% of SKG mice. SKG skin lesions showed a histological phenotype similar to human Ps with elevated constitutive levels of IL-23a(p19) and increased secretion of both IL-17 and IL-22, 7 days after curdlan. Neutralisation of both IL-23 and IL-22 suppressed development of skin inflammation and IL-17A-deficient SKG mice were partially spared. GF-SKG mice failed to develop significant skin inflammation after curdlan; however, colonisation with a limited microbiota induced mild psoriasis-like inflammation. Tregs modulated the severity of skin inflammation through the suppression of IL-23 secretion. Intradermal injection of IL-23 induced IL-22 mediated, microbiota dependent psoriasis-like inflammation in naïve SKG mice. Conclusions: In curdlan-treated SKG mice IL-23-driven psoriasis-like inflammation is induced in the setting of SpA. The skin inflammation recapitulates several features of human Ps and is dependent on the relative contributions of IL-23-mediated IL-17, IL-22, microbiota and the balance of Tregs and T effector cells.

Royal Newcastle Centre, John Hunter Hospital, Newcastle, NSW Aim: To evaluate the effectiveness of the fracture liaison service (FLS) to prevent osteoporotic re-fractures Methods: All patients aged ≥ 50 years with a minimal trauma fracture (fall from a standing height or less impact) between July 2010 and December 2010 at John Hunter Hospital (FLS hospital) were compared to patients at another tertiary hospital (non-FLS hospital) draining a similar patient demographic without a fracture liaison service. The hospital computer system was used to collect information on baseline patient characteristics (age, gender, baseline fracture site) as well as re-fracture rates in a 3 year follow up period. Mortality data was collected from NSW Death and Birth registries. Results: 515 patients at the FLS hospital and 416 patients at the non-FLS Hospital were included in the study. Over 3 years, 63/515 (12%) patients at the FLS hospital and 70/416 (17%) patients at the non-FLS hospital had a minimal trauma re-fracture. All patients were analyzed in an intention-totreat analysis regardless of whether they were seen in the fracture liaison clinic. Statistical analysis using proportional hazards models in the presence of a competing risk of death from any cause was used. After adjustments for baseline characteristics, there was a ∼30% reduction in rate of any re-fracture at the FLS hospital (HR 0.67, CI 0.47–0.95, p-value 0.025).There was also a ∼40% reduction in major re-fractures (hip, spine, femur, pelvis or humerus) (HR 0.60, CI 0.39–0.91, p-value 0.017).


3

Abstracts

ARA10 IDIOPATHIC INFLAMMATORY MYOSITIS IS ASSOCIATED WITH SYSTEMIC SCLEROSIS Maundrell A1, Chaudhary S2, Blumbergs P3, Proudman S4, Limaye V4 1

Royal Adelaide Hospital The University of Adelaide 3 SA Pathology, the University of Adelaide 4 Royal Adelaide Hospital, the University of Adelaide, South Australia 2

Aim: The aim of this study was to describe the clinical, histopathological and serological features of idiopathic inflammatory myositis (IIM) patients who have an overlap syndrome with systemic sclerosis (SSc), and to determine whether this group is distinct from IIM patients who do not have other connective tissues diseases (CTD). Methods: The South Australian (SA) Myositis Database is a registry of adult patients with biopsy-proven IIM subsequent to 1980. The following was determined from this database: presence/absence of associated CTD, histological details (lymphocytic invasion of myofibres, polyfocal polyphasic myonecrosis, myofibre regeneration, perifascicular atrophy, expression of MHC1/MHCII, detection of CD45/CD68), presence/absence of myositisspecific (MSA) or myositis-associated (MAA) antibodies. Four groups of patients were defined: IIM alone; IIM with SSc; IIM with mixed connective tissue disease (MCTD); IIM with other CTD, namely, primary Sjögren’s syndrome (PSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods: The discovery sample was drawn from the Australian CLARITY JIA biobank. Rs2476601 was genotyped in 413 cases (67% female, mean age at recruitment 9.1 years) and 690 healthy controls (42% female, mean age at recruitment 7.1 years). We used logistic regression to assess the association of rs2476601 with JIA in the total sample (males and females). We then explored the role of sex in this association: we adjusted the regression analysis for sex, stratified by sex, and performed a genotype-bysex interaction analysis. We sought to replicate the sex-specific associations in an independent JIA case-control sample collected from the USA and Norway and held at the Children’s Hospital of Philadelphia (1008 JIA cases and 9287 controls). Analyses were performed using Stata or PLINK. Results: PTPN22 rs2476601 was associated with JIA in both datasets (Discovery OR = 1.71, 95% CI 1.26–2.33, p = 0.00066; Replication OR = 1.30, 95% CI 1.09–1.55, p = 0.0068). The association remained when adjusted for sex (Discovery OR = 1.63, 95% CI 1.18–2.24, p = 0.0028; Replication OR = 1.30, 95% CI 1.08–1.56, p = 0.0051). Discovery sample sexstratified analyses demonstrated association in females (OR = 2.35, 95% CI 1.52–3.63, p = 0.00011) but not males (OR = 0.91, 95% CI 0.52–1.60, p = 0.75).This was also observed in the replication sample (Female OR = 1.38, 95% CI 1.09–1.73, p = 0.0068; Male OR = 1.19, 95% CI 0.88–1.63, p = 0.26). There was evidence for genotype-by-sex interaction (p interaction = 0.0087). Conclusions:We have demonstrated that the association between PTPN22 rs2476601 and JIA appears restricted to females, helping to explain the greater number of females that develop this disease.

Results: Among patients with IIM, a significantly greater proportion had SSc 33/656 (5%) than MCTD (12/656, p = 0.002), PSS (12/656, p = 0.002), SLE (10/656, p < 0.001) and RA (7/656, p < 0.0001). Polymyositis was the most common IIM diagnosis in all groups. Those with IIM/SSc had significantly less frequent lymphocytic invasion of myofibres than those with IIM alone (OR 3.97, p = 0.0008). In those with IIM/SSc, at least one MSA was identified in 11/15 (73%) patients, with anti-PM-Scl and anti-Ro being the most common (both 6/15, 40%). MSA/MAA were more commonly detected in patients with IIM/SSc than those with IIM alone (OR 5.25, p = 0.005), with significantly higher frequency of antibodies to PM-Scl (p < 0.0001), Scl70 (p < 0.0001) and Ro (0.002). Conclusions: The higher prevalence of SSc in IIM together with the more frequent detection of autoantibodies in this group suggests that these conditions may be pathogenetically linked. Vigilance for a second diagnosis of SSc in IIM patients with anti-Pm-Scl antibodies is warranted. ARA11 THE ASSOCIATION OF PTPN22 RS2476601 WITH JUVENILE IDIOPATHIC ARTHRITIS IS SPECIFIC TO FEMALES Chiaroni-Clarke R1, Li Y2, Munro J3, Chavez R1, Scurrah K4, Pezic A5, Akikusa J3, Allen R3, Piper S6, Becker M7, Thompson S8, Lie B9, Flato B10, Forre O10, Punaro M11, Wise C11, Saffery R1, Finkel T12, Hakonarson H2, Ponsonby A1, Ellis J1 1

Murdoch Childrens Research Institute; University of Melbourne, Parkville, Australia 2 Children’s Hospital of Philadelphia; University of Pennsylvania, Philadelphia, USA 3 Murdoch Childrens Research Institute; Royal Children’s Hospital, Parkville 4 University of Melbourne, Parkville, Australia 5 Murdoch Childrens Research Institute 6 Monash Children’s Hospital, Clayton, Australia 7 Children’s Mercy Hospital, Kansas City 8 Cincinnati Children’s Hospital Medical Centre, Cincinnati, USA 9 Oslo University Hospital; University of Oslo, Oslo, Norway 10 Oslo University Hospital 11 Texas Scottish Rite Hospital for Children, Dallas 12 Nemours Children’s Hospital, Orlando, USA Aim: A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this female bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. The JIA genetic risk variant, PTPN22 rs2476601, has been reported to show female-specific association in type 1 diabetes. We sought to determine whether rs2476601 exhibits a female-specific association in JIA.

4


Abstracts

ARA12 THE ASSOCIATION OF HYPOCOMPLEMENTEMIA WITH DISEASE ACTIVITY IN SYSTEMIC SCLEROSIS Esposito J1, Stevens W1, Rabusa C1, Sahhar J2, Walker J3, Thakkar V4, Major G5, Roddy J6, Zochling J7, Proudman S8, Nikpour M1 1 Departments of Rheumatology and Medicine, the University of Melbourne at St Vincent’s Hospital, Melbourne, Victoria, Australia 2 Department of Rheumatology, Monash Medical Centre, Melbourne, Victoria, Australia 3 Department of Rheumatology, Flinders Medical Centre, South Australia, Australia 4 Departments of Rheumatology and Medicine, the University of Melbourne at St Vincent’s Hospital, Department of Rheumatology, Liverpool Hospital, School of Medicine, University of Western Sydney, New South Wales, Australia 5 School of Medicine and Public Health, University of Newcastle, New South Wales, Australia 6 Department of Rheumatology, Royal Perth Hospital, Perth, Western Australia, Australia 7 Department of Rheumatology, Menzies Institute Tasmania, Hobart, Tasmania, Australia 8 Department of Rheumatology, Royal Adelaide Hospital and Discipline of Medicine, University of Adelaide, South Australia, Australia

Aim: Hypocomplementemia constitutes one of the ten parameters needed to determine the European Scleroderma Study Group (EScSG) disease activity score. However few studies have investigated the clinical manifestations and relationship to disease activity of hypocomplementemia in systemic sclerosis (SSc).The objective of this study was therefore to determine the clinical features of hypocomplementemia in SSc and define its utility as a marker of disease activity. Methods: 1140 patients from the Australian Scleroderma Cohort Study, comprising a total of 2867 visits were included. These patients fulfilled the 2013 ACR classification criteria for SSc. Demographic, serological and clinical data obtained through annual review were analysed using univariate methods. Linear and logistic regression, together with generalised estimating equations were used to determine the independent correlates of hypocomplementemia ever, and at each visit, respectively. Results: At least one episode of hypocomplementemia (low C3 and/or low C4) occurred in 24.1% of patients over a follow-up of 3.4 ± 1.7 years, these patients were more likely to be seropositive for anti-ribonuclear protein (odds ratio [OR] = 3.8, p = 0.002), anti-Ro (OR = 2.2, p = 0.002), antiSmith (OR = 6.3, p = 0.035) and anti-phospholipid antibodies (OR = 1.4, p = 0.021) and display features of mixed connective tissue disorder (OR = 1.5, p = 0.007), specifically polymyositis (OR = 16.0, p = 0.012). No association was found between hypocomplementemia and the EScSG disease activity score (calculated without hypocomplementemia to avoid over correlation) or any of its components (including ESR). Among patients with overlap disease features (n = 221), those who were hypocomplementemic were more likely to have a lower BMI (OR = 0.9, p < 0.0005), digital ulcers (OR = 1.6, p = 0.034), tendon friction rubs (OR = 2.4, p = 0.037) and a forced vital capacity 0.45 mmol/L. Results: The overall prevalence of gout was 5.2%. Males were significantly more likely to have gout than females (8.5% vs 2.1%, p < 0.001). The overall prevalence of hyperuricaemia was 7.2%, with being male again identified as a significant risk factor (12.3% vs 2.4%, p < 0.001). Univariate analysis showed that both gout and hyperuricaemia were significantly associated with age, hypertension, body mass index, renal disease and cardiovascular disease. Current smoking was associated with a decreased risk of gout (OR 0.4, p = 0.02). There was no significant difference reported in quality of life (mean SF-36) scores in either the gout or hyperuricaemic participants, compared to unaffected individuals. Conclusions: In the South Australian population the prevalence of gout and hyperuricaemia is high, comparable to New Zealand. Gout and hyperuricaemia are associated with hypertension, obesity, kidney and heart disease, emphasising the importance of cardiovascular risk factor management for this disease. Similar to other recent population studies, current smoking was associated with a reduced risk of gout.

Aim: To evaluate the effects of vitamin D on knee pain and structural changes in knee OA patients with low vitamin D. Methods: A multicentre, parallel-randomized, placebo-controlled and doubleblind clinical trial in patients with symptomatic knee OA and a low 25(OH)D


5

Abstracts

ARA15 BONE MARROW LESIONS DETECTED BY TWO MRI SEQUENCES ASSOCIATE WITH SEVERITY OF KNEE OSTEOARTHRITIS Muratovic D1, Cicuttini F2, Wluka A2, Wang Y2, Findlay D3, Otto S4, David T5, Collings S5, Mercer G6, Julia H7, Lee Y7, Kuliwaba J8 1

Bone and Joint Research Laboratory, Sa Pathology Discipline of Orthopaedics and Trauma, the University of Adelaide, Adelaide 2 Department of Epidemiology Preventive Medicine, Monash University, Melbourne 3 Discipline of Orthopaedics and Trauma, the University of Adelaide, Adelaide 4 Anatomical Pathology, SA Pathology, Adelaide 5 Department of Radiology, Royal Adelaide Hospital, Adelaide 6 Department of Orthopaedics, Repatriation General Hospital, Adelaide 7 Bone and Joint Research Laboratory, SA Pathology, Adelaide 8 Bone and Joint Research Laboratory, SA Pathology Disciplines of Orthopaedics and Trauma and Anatomy and Pathology, the University of Adelaide, Adelaide Aim: Bone Marrow Lesions (BMLs) correlate strongly with severity of knee OA symptoms and osteo-chondral structural degeneration. Tissuelevel changes based on the presence/absence of BMLs have not been comprehensively investigated. Thus, the aims of this study were to characterise the bone and marrow changes in BMLs, to address how their presence relates to changes in the overlying cartilage, and to investigate possible differences when imaged using specific MRI sequences. Methods: Tibial plateaus (TP) were obtained from 56 patients (28 females, 28 males), aged 51–86 years, undergoing knee arthroplasty for OA. To identify BMLs, MRI scans were performed ex vivo using T1 and PDFSweighted sequences. Microstructure and bone turnover indices were quantitated separately for subchondral plate and trabecular bone. Histopathology of the whole osteo-chondral unit was examined using the OARSI grading system and by routine pathologist assessment.

Results: MRI detected BMLs in 78% of TP, BML-1 (PDFS) represented 48%, BML-2 (PDFS + T1) 30%. 22% of TP had no BML. Bone and marrow of BMLs were characterised by more bone marrow oedema (p = 0.02) and necrosis (p = 0.005), thicker subchondral plate (p = 0.002) and higher trabecular bone volume with more plate-like structure (p = 0.0004), and increased plate/trabeculae bone formation (p = 0.003) compared to no BMLs. There was also reduced cartilage volume (p = 0.008), with greater loss of proteoglycans (p = 0.004). BML-1 compared to BML-2 had higher cartilage volume (p = 0.003) and number of thick-walled vessels (p = 0.001). BML-2 had more bone marrow fibrosis (p = 0.002), necrosis (p = 0.01) and fibro-vascular cysts (p = 0.04), compared to BML-1. Conclusions: This study clearly confirms that BML presence/absence is related to the degree of structural and cellular change in the osteo-chondral unit. Furthermore, presence/absence of BMLs in specific MRI sequences differentiated 3 stages of structural progression. Therefore, sequencespecific BMLs could act as potential MRI biomarkers to identify individuals with more severe OA and for development and monitoring of new therapies.

6

ARA16 DISRUPTIVE PATHOLOGY RATHER THAN DEGENERATIVE OR DISCRETE TEAR ARE ASSOCIATED WITH KNEE PAIN, INCREASING BONE MARROW LESION VOLUME AND A PROXY FOR TOTAL KNEE ARTHROPLASTY: LONGITUDINAL ANALYSIS FROM THE OSTEOARTHRITIS INITIATIVE Eathakkattu Antony B1, Driban J2, Price L3, Lo G4, Ward R5, Nevitt M6, Lynch J6, Eaton C7, Ding C1, McAlindon T2 1

Menzies Research Institute Tasmania, University of Tasmania Division of Rheumatology, Tufts Medical Center, Boston, USA 3 The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, USA 4 Division of Rheumatology, Baylor College of Medicine, Houston, USA 5 Division of Radiology, Tufts Medical Center, Boston, USA 6 Department of Epidemiology and Biostatistics, University of California at San Francisco, USA 7 Center for Primary Care and Prevention, Alpert Medical School of Brown University, Pawtucket, USA 2

Aim: Meniscal pathology increases the risk for the incidence and progression of knee osteoarthritis but it is unclear if different types of pathology are associated with symptomatic and structural progression.We aimed to explore the association of different types of knee meniscal pathology with knee pain, bone marrow lesion (BML) volume, and a proxy for total knee arthroplasty (TKA). Methods: We selected a convenience sample of the Osteoarthritis Initiative (OAI) who had symptomatic knee osteoarthritis and complete data for the OAI Bone Ancillary Project. A musculoskeletal radiologist reviewed the 24-month OAI magnetic resonance images for meniscal pathology by location using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) meniscal tear classification system. We reclassified the types of pathology into 5 categories: normal, degenerative signal, morphological deformity, any tear, and maceration. Outcomes included WOMAC knee pain and BML volume at 24 and 48 month visits. We used an algorithm developed by Escobar et al (2003) and adapted to OAI by Riddle et al (2014) to define the appropriateness for TKA. Results: 463 participants were included in the analysis with mean age of 63 (9.2) years, 53% male, body mass index 29.6 (4.6) kg/m2, 71% KellgrenLawrence grade > 1. Morphological deformity and maceration, but no other types of pathology, were associated with BML volume (OR: 5.85, 95% CI: 3.40, 10.06), change in BML volume (OR: 3.12, 95% CI: 1.87, 5.19), and a proxy for TKA (OR: 2.62, 95% CI: 1.38, 4.95). Maceration was associated with knee pain (OR: 2.82, 95% CI: 1.79, 4.43) but not with increase in knee pain. Conclusions: Among the five categories of meniscal pathologies, disruptive pathology (i.e., morphologic deformity or maceration) rather than degenerative or discrete tear was associated with knee pain, structural changes and a later clinical state that is proxy for TKA. This suggests that only pathologies that severely impair normal load distribution properties of meniscus can cause damage to the knee joint.


Abstracts

ARA17 USE OF NON-PBS-FUNDED ‘OFF-LABEL’ RITUXIMAB IN RHEUMATOLOGY Liew D1, Morrisroe K2, Romas E2, Buchanan R3, Foote A4 1

Austin Hospital, Melbourne and Northern Hospital, Melbourne St Vincent’s Hospital, Melbourne and the University of Melbourne Austin Hospital, Melbourne, Northern Hospital, Melbourne and University of Melbourne 4 Northern Hospital, Melbourne, Monash Health, Melbourne and Monash University, Melbourne 2 3

Aim: Rituximab is approved for the PBS-funded treatment of rheumatoid arthritis in Australia, however non-PBS-funded ‘off-label’ rituximab (OLR), informed by varying levels of evidence, is used to treat a variety of other conditions. There is limited published data regarding usage, screening, side effects and response to OLR for rheumatological indications. Methods: A retrospective chart review was completed at two tertiary public hospitals in Melbourne for OLR spanning January 2009-December 2013. Cases were identified from the pharmacy department of each hospital. Clinical notes and pathology records were analysed for demographic information, dosage regimens and indication. For rheumatological indications, previous therapy, screening, side effects and response were measured. Results: In the five-year period there were 205 clinical episodes where OLR was given, with a total cumulative dosage of 470.8 g. Of these, 79 cases were for a rheumatological indication, with a cumulative dosage of 140.3 g (29.8% of total). Patients with rheumatological indications were younger (median 40 y vs 51 y) and more likely to be female (OR 4.07 (2.18, 7.61)) than those with non-rheumatological indications. Small-vessel vasculitis (including ANCA-associated) was the most common rheumatological indication for OLR (47%), followed by lupus nephritis.Treatment response was inconsistently recorded, although clinician-assessed complete response was documented in the majority of these patients. Over one-third (28/79) of OLR approvals for rheumatological indications had not had any input from the hospital’s rheumatology unit. Conclusions: Twenty-nine percent of hospital-funded OLR is for rheumatological indications. It is most commonly used to treat small vessel vasculitis, including ANCA-associated vasculitis for which level one evidence of efficacy exists. The majority of episodes resulted in clinician assessed complete responses. Our data supports the proposition that there is a discrepancy between the efficacy of OLR and existing funding models. Screening, side effects, and efficacy measures are inconsistent and further study is required. ARA18 IS SERUM LEVEL OF 25-HYDROXYVITAMIN D ASSOCIATED WITH THE RISK OF HIP REPLACEMENT FOR OSTEOARTHRITIS? RESULTS FROM A PROSPECTIVE COHORT STUDY Hussain S1, Daly R2, Wang Y1, Shaw J3, Magliano D3, Graves S4, Ebeling P1, Wluka A1, Cicuttini F1 1

Monash University Deakin University 3 Baker IDI 4 University of Adelaide 2

Aim: Evidence is conflicting for the association between serum 25-hydroxyvitamin D[25(OH)D] concentrations and risk of hip osteoarthritis.The aim of this prospective cohort study was to determine whether serum 25(OH)D concentrations were associated with the incidence of hip replacement for osteoarthritis.

Results: Over an average 9.1 (SD 2.7) years of follow-up, 90 males and 111 females had hip replacements for osteoarthritis. In males, a one SD increase in 25(OH)D concentrations was associated with a 25% increased incidence of hip replacement for osteoarthritis (HR 1.25, 95% CI 1.02, 1.56), with a dose response relationship observed by quartiles of 25(OH)D concentration (P for trend 0.04). No significant association was observed in females (HR 1.10 per SD increase in 25(OH)D concentrations, 95% CI 0.87, 1.39). Conclusions: Higher serum 25(OH)D concentrations were associated with an increased risk of hip replacement for osteoarthritis in males, but not in females. The mechanism for the association warrants further investigation.

RHPA Oral Abstracts RHPA1 HOSPITALISATIONS AND DIRECT COSTS RELATED TO OSTEOPOROTIC FRACTURES AND RISK OF FRACTURERELATED RE-ADMISSIONS IN WESTERN AUSTRALIA: A 10-YEAR REVIEW USING THE LINKED WA HOSPITAL MORBIDITY DATA SYSTEM Briggs A1, Sun W2, Miller L2, Geelhoed E3, Huska A2, Inderjeeth C4 1

Curtin University Department of Health, WA 3 University of Western Australia 4 North Metropolitan Health Service, WA; University of Western Australia 2

Aim: Fractures related to osteoporosis impose a substantial personal and health system burden. Once an initial fracture is sustained, the risk of re-fracture rises markedly. The aim of this study was to examine the costs associated with this fracture cascade. Specifically we aimed to quantify direct hospitalisation costs to Western Australia (WA) for osteoporosisrelated fractures, and estimate risk of re-admission after incident fracture using linked data. Methods: All hospitalisation records for WA residents aged ≥50 years admitted to a WA hospital between 2002–2011 due to osteoporotic fractures were extracted from the WA Hospital Morbidity Data System. Data linkage enabled identification of the first (index) fracture admission, determination of subsequent osteoporotic fracture-related re-admissions, and quantification of total admission costs and bed days. Cox proportional hazard models assessed factors influencing first readmission for fracture. Results: 5,326 patients were admitted to WA hospitals for an index fracture. Of the 2,037 (38.2%) patients who sustained a re-fracture requiring readmission, 1,223 (23.0%) sustained one re-fracture episode, 453 (8.5%) sustained two, and 361 (6.8%) sustained ≥3 re-fracture episodes requiring readmission. Cost of index admissions was $AU57,007,262 while $AU48,948,623 was associated with re-admissions (CPI-adjusted to 2011/ 12). Cumulative probability of readmission within 6 months of the index admission was 20% (males) and 17% (females). Conclusions: Osteoporotic fracture-related hospitalisations impose a substantial financial impact to WA, exceeding $AU100M in a decade. Considering the large system costs, policy and programmes to improve identification of index fractures and initiation of osteoporosis treatments and primary prevention initiatives are justified.

Methods: This study examined 9,135 participants from the Australian Diabetes, Obesity and Lifestyle Study who had serum 25(OH)D measured in 1999–2000 and were aged ≥40 years at the commencement of hip replacement data collection. The incidence of hip replacement for osteoarthritis during 2002–2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. The association between serum 25(OH)D and incidence of hip replacement for osteoarthritis was estimated by hazard ratio [HR, 95% confidence interval (CI)] with age as the time-scale. Since a sex interaction was identified, all analyses were stratified by sex and adjusted for body mass index, smoking status, ethnicity, physical activity, season of blood collection, latitude, area-level disadvantage, diabetic status and hypertension.


7

Abstracts

RHPA2 THE CONSENSUS ON EXERCISE REPORTING TEMPLATE (CERT CHECKLIST): A DELPHI STUDY INVESTIGATING A STANDARDISED METHOD FOR REPORTING EXERCISE PROGRAMS Slade S1, Dionne C2, Underwood M3, Buchbinder R1 1

Monash University and Cabrini Hospital, Melbourne, Australia Laval University, Québec, Canada 3 The University of Warwick, Coventry, UK 2

Aim: Exercise is effective, integral to health and important for people with chronic health conditions. A systematic review of exercise for chronic conditions reported suboptimal descriptions of interventions and concluded that this hinders replication and implementation. Without explicit descriptions, clinicians, patients and researchers remain unclear about effective programs. The aim was to develop a standardised method for reporting essential exercise program details evaluated in clinical trials. Methods: A Protocol has been accepted in BMJ Open. A modified Delphi technique was used to gain consensus among an international panel of experts identified by systematic review authorship, international research and clinical profile and peer referral. An online survey of 42 questions was developed from our systematic review. Experts from 14 countries indicated item importance on a scale of 0–10 and gave free text comments. We used three sequential rounds of anonymous online questionnaires.The final draft template will be piloted on a random sample of systematic reviews and RCTs of exercise. Modifications will be made and final approval sought from the expert panel. Results: There were 57/137 respondents in Round 1 (42%) with 10 items accepted in original format and 14 reformatted for Round 2 which had 53/57 respondents (93%). Sixteen items were distributed for Round 3 which had 48/54 respondents (88%). The final core set was 16 items and 520 comments were thematically analysed. The final template was modeled according to the CONSORT Statement and TIDieR Checklist and, following final panel review, we will develop an explanatory statement and implementation strategies such as journal endorsement for manuscripts and peer-review and a CONSORT Item 5 extension. The CERT checklist is registered on the Equator Network. Conclusions: The CERT checklist will improve reporting of exercise interventions in clinical trials; increase clinical uptake of effective exercise programs; enable research replication; and improve patient outcomes. RHPA3 WHAT HAVE WE LEARNT FROM 10 YEARS OF BIOLOGICAL DISEASE MODIFYING AGENTS ON THE PHARMACEUTICAL BENEFIT SCHEME? Hopkins A1, Proudman S2, Vitry A1, Sorich M3, Cleland L2, Wiese M1 1 University of South Australia, Sansom Institute for Health Research and School of Pharmacy and Medical Sciences 2 Royal Adelaide Hospital, Department of Rheumatology 3 Flinders University, Department of Clinical Pharmacology, SA

Conclusions: The impact of strict initiation and continuation rules, plus a modest price reduction over time, on an overall bDMARDs expenditure that continues to increase, is uncertain. It is also unclear if any lessons have been learnt from the introduction of these systems, with expenditure predictions still performing poorly. Present and future opportunities that could be explored include utilisation of data from authority prescription requests that have been collected for the past 10 years, which may help in the strategic development, regulation and use of biosimilars. RHPA4 THE ASSOCIATION OF FAT MASS AND ADIPOKINES WITH FOOT PAIN IN A COMMUNITY COHORT Walsh T1, Gill T2, Shanahan EM3, Hill C4 1

Flinders University The University of Adelaide Flinders University, The Repatriation General Hospital 4 The University of Adelaide, The Queen Elizabeth Hospital, SA 2 3

Aim: To determine if fat mass and adipokines are (1) associated with prevalent foot pain, and (2) are predictive of future foot pain. Methods: The North West Adelaide Health Study is a cohort study located in Adelaide, South Australia. Three phases of data collection have been conducted, 2000–2002 (Stage 1), 2004–2006 (Stage 2) and 2008–2010 (Stage 3). In Stage 2, participants were asked in if they had foot pain, aching or stiffness on most days. In Stage 3, they were asked if they had foot pain, aching or stiffness on most days, over the past month. In Stage 2 those aged ≥35 years had serum analyses for TNF-α and IL-6, those aged ≥50 years had dual-energy X-ray absorptiometry scans, providing data to calculate fat mass index (FMI). Confounding variables from Stage 2 such as activity levels, alcohol intake, age, body mass index (BMI), depression, diabetes, self-reported doctor-diagnosed arthritis, sex and smoking history were used in logistic regression analysis to determine if fat mass and adipokines were associated with foot pain. Results: In unadjusted analysis, TNF-α and IL-6 were significantly associated with prevalent foot pain and was predictive of future foot pain. However, after multivariate analysis, they were not associated with foot pain. FMI, depression, poor general health, diabetes, osteoarthritis, arthritis (type unknown) and RA were associated with prevalent foot pain after multivariate analysis. Only FMI (OR = 1.000061, 95% CI 1.000018– 1.000104), arthritis (OR = 1.99, 95% CI 1.36–2.91) and depression (OR = 1.90, 95% CI 1.04–3.45) were significant predictors of developing future foot pain. Conclusions: Increased FMI, but not BMI,TNF-α or IL-6, was associated with both prevalent and predictive of future foot pain. These results suggest that body composition may be more important than body weight and adipokines (other than those tested for in this study) could be responsible.

Aim: Biological disease modifying anti-rheumatic drugs (bDMARDs) were among the first high cost medicines to be subsidised in Australia, and as such posed several challenges for providing timely access at a cost individuals and the community could afford. A unique subsidy scheme was developed which requires clinicians to complete written authority applications for initial use and response criteria to permit continuation of treatment. In this study we assessed the uptake of bDMARDs since subsidisation and the expenditure on the newer agents’ tocilizumab, certolizumab pegol and golimumab in rheumatoid arthritis (RA). We use this is an example of current and future challenges to the use of high cost medicines in Australia. Methods: A longitudinal analysis of PBS cost expenditure and dispensing data for available bDMARDs was conducted between 2003 and 2013. National bDMARD utilisation was evaluated through the Defined Daily Doses (DDDs)/1,000 inhabitants/day. Results: The national utilisation of bDMARDs in the treatment of RA increased from 0.006 DDDs/1,000 inhabitants/day in 2003 to 0.503 in 2012, similarly the incurred cost to the PBS and RPBS increased from $3 million to $281 million. Four years after their introduction tocilizumab, certolizumab pegol and golimumab accounted for a combined expenditure of approximately $66 million in 2013, 120% over the predicted estimate.

8


Abstracts

RHPA5 WHAT ARE PATIENT BELIEFS AND PERCEPTIONS ABOUT EXERCISE FOR NON-SPECIFIC CHRONIC LOW BACK PAIN? A SYSTEMATIC REVIEW OF QUALITATIVE STUDIES Slade S1, Patel S2, Underwood M2, Keating J3 1

Monash University and Cabrini Hospital, Melbourne, Australia The University of Warwick, Coventry, UK 3 Monash University, Melbourne, Australia 2

Aim: Clinical practice guidelines recommend individualized exercise with consideration of patient preferences and it is likely that observed moderate effects will improve if programs align with participant preferences.To perform a systematic review and meta-synthesis of qualitative studies that explored peoples’ beliefs about exercise for low back pain. Methods: The review was conducted according to Cochrane Collaboration Guidelines and reported according to the PRISMA statement. Eight electronic databases were searched until July 2012 and inclusion criteria were: English-language studies published in peer-reviewed journals; participants consulted a practitioner who prescribed exercise; > 80% of participants had back pain longer than six weeks; reported data enabled evaluation. Pairs of independent reviewers screened titles and abstracts, extracted data, appraise method quality, conducted thematic analysis and synthesized the results in narrative format Results: From a search yield of 3431 titles, 48 papers were read in full and 15 papers were included for method quality assessment, data extraction and data synthesis. Four key themes emerged: 1) Perceptions and classification of exercise; 2) Role and impact of the health professional; 3) Exercise and activity enablers/facilitators; 4) Exercise and activity barriers. Exercise skill and experience require consideration in program design. Care-seekers perceive that when an intervention interferes with everyday life, is ineffective or too difficult they will discontinue. Questions suited to collect information about patient preferences have been collated into a checklist. Conclusions: People are likely to engage in exercise programs that are designed with consideration of their preferences, fitness levels and exercise experience. In the area of exercise and low back pain research there is a paucity of qualitative data. This contrasts with over 500 RCTs listed in the Cochrane Library. Consideration must be given to participant facilitators and barriers when designing exercise programs. Research is recommended to test effectiveness of patient preferences input. RHPA6 IMPROVING PHYSIOTHERAPY WORKFORCE READINESS IN BEST PRACTICE MANAGEMENT OF RHEUMATOID ARTHRITIS USING E-LEARNING: A MIXED METHODS STUDY Fary R1, Slater H1, Gardner P1, Jordan J2, Chua J3, Briggs A4 1

Curtin University Healthsense (Aust) Pty Ltd Department of Health, WA; Curtin University 4 Curtin University; Arthritis Osteoporosis Victoria 2 3

assisted RA learning with key elements including: i) providing in-depth insight into patient and treating clinician perspectives, ii) more clinicallyfocussed than lectures, iii) a comprehensive, centralised learning resource, iv) a holistic approach to chronic disease management, and v) a userfriendly interface and information. Conclusions: Embedding RAP-eL in the entry-level physiotherapy program was very effective in improving students’ self-reported confidence in knowledge and skills to manage people with RA, specific RA clinical knowledge, and likely practice behaviours. Students identified RAP-eL as an effective, innovative and useful educational resource for the entry-level curriculum. RHPA7 FACTORS AFFECTING CHANGE IN CHILDREN WITH JOINT HYPERMOBILITY SYNDROME: RESULTS OF A PROSPECTIVE LONGITUDINAL STUDY Pacey V1, Tofts L2, Adams R3, Nicholson L3 1

MacQuarie University The Children’s Hospital at Westmead 3 The University of Sydney 2

Aim: To determine whether patient characteristics can predict change in health-related quality of life (HRQOL) scores or change in the number of painful joints reported by children with Joint Hypermobility Syndrome at eighteen months following the initial assessment. Methods: Children with JHS and one of their parents completed the Pediatric Quality of Life Inventory 4.0 Generic Core Scale, the Multidimensional Fatigue Scale and the Pediatric Pain Questionnaire. Demographic and anthropometric measures, joint hypermobility, foot posture, strength, balance, walking capacity, physical activity and reported symptoms were recorded at baseline and again 18 months later. Stepwise multiple regression was undertaken to determine whether any combination of measures could predict the change in HRQOL and number of painful joints reported 18 months following initial assessment. Results: Eighty nine children (50 girls) aged 6–16 years were assessed at baseline. Sixty-three children (35 girls, mean age 11.2 years) were assessed 18 months later. HRQOL remained stable in 49 children, improved in 6, and declined in 8 children.Thirty-four percent of the variance in the change in child-reported HRQOL scores 18 months following baseline could be accounted for by four baseline variables – HRQOL score, body mass index centile for age, foot posture and the total number of reported painful joints (p < 0.001). For the number of painful joints reported 18 months later, child-reported fatigue and the number of painful joints reported at baseline accounted for 37% (p < 0.001) of the variance in the change scores. Conclusions: Factors amenable to change, such as BMI for age and child-reported fatigue, contribute to the decline in both the HRQOL and increase in number of painful joints experienced by children with JHS over an 18 month period. Management strategies aimed at improving these factors may assist in minimising the impact of JHS in some children’s daily lives.

Aim: Entry-level physiotherapy education in rheumatology is limited. This study aimed to 1. Evaluate the effectiveness of embedding an interactive Rheumatoid Arthritis for Physiotherapists e-Learning (RAP-eL) package into an entry-level physiotherapy program in upskilling students in bestpractice RA management, and 2. Determine its acceptability as a learning tool in this cohort. Methods: RAP-eL was embedded within the entry-level physiotherapy program at Curtin University, WA, in 2014. Students were given 5 weeks access to RAP-eL. Pre- and immediately post-RAP-eL, students completed an online outcomes questionnaire. The primary outcome measure was self-reported change in confidence in knowledge (possible total 9–45) and skills (possible total 8–40) post-RAP-eL intervention. Secondary outcomes included responses to RA-relevant clinical questions and two clinical vignettes. Purposive sampling was used to recruit 23 students to participate in a nested qualitative study to capture the students’ experience of RAP-eL. Results: 137 students (mean (SD) age 23 (3.5), 72% female) participated. Significant improvements were observed in self-reported confidence in knowledge (mean change 18.5, 95% confidence interval (95% CI) 17.6 to 19.4, p < 0.001) and skills (mean change 14.9, 95% CI 13.9 to 15.9, p 0.05). During US assessment, joint effusion due to rheumatoid arthritis, ganglion cyst beneath to median nerve and bifid median nerve were seen in three patients. Conclusions: Diagnostic ultrasonography maybe a useful non-invasive confirmatory test in the patient whom there is a strong clinical suspicion of CTS. Before surgery of CTS, patients were evaluated anatomically and additional differential diagnosis can be provided by US. US maybe preferred as the initial step instead of electrophysiological studies.

Conclusions: The majority of final year medical students would order an MRI as part of the initial approach for acute radicular back pain. A short intervention reviewing red-flag indicators for appropriate use of imaging was able to reduce this. However this observation (although limited to a © 2015 The Authors Internal Medicine Journal © 2015 Royal Australasian College of Physicians Internal Medicine Journal (2015) 45 (Suppl. 2): 1–46

11

Abstracts

ARP9 THE APPLICATION OF DEXAMETHASONE IONTOPHORESIS IN CARPAL TUNNEL SYNDROME Baklaci K

Conclusions: Each of three groups except placebo group had favorable effects on nerve conduction studies, patient based assessments and these effects last significantly longer and more apparent in splinting group. Patient satisfaction for the treatment was found maximum in physical therapy plus splinting group and minimum in plasebo group.

Turkish Armed Forces Health Corps, Turkey Aim: The aim of this study is to demonstrate the effects of the conservative treatment of carpal tunnel syndrome (CTS) by means of steroid antiinflammatory drugs applied by iontophoresis. Methods: Fifteen female patients (age 34.4 ± 7.6 years) participated in this study. Four of them had unilateral, and 11 had bilateral, idiopathic CTS. The onset of symptoms was from 3 weeks to 3 months prior to diagnostics and therapy. The diagnose was established by electromyographic examination. Dexamethasone, 8 mg water solution for the parenteral use, was administered daily, at the wrist region, by iontophoresis (150 mA/min). Treatment was applied during 15 consecutive days. The modification of daily activities was recommended to all of the patients, during and after the treatment. Follow-up period was 12 months. Pain was evaluated by VAS other symptoms (numbness, night pain, limitations of daily activities etc.), were evaluated by self-administered questionnaire, and the same set of EMG tests were used for follow-up. Results: In 13 patients, because of symptoms persistence, the same therapeutic protocol was repeated after 3 weeks. In two patients with bilateral CTS (15.4%), bilateral open surgery was performed, because of the progression of symptoms and EMG changes. In the other patients, pain was significantly reduced (p < 0.01), as well as the other symptoms. No significant changes of median nerve distal latency (DL) occurred during the first three months of follow-up, as well as the changes in median sensory nerve conduction velocity (SNCV) in hand region.€¨¨At the 6 months follow-up, significant shortening of median nerve DL (p < 0.01), occurred. At the end of follow-up period, normal finding was registered in 61.5% cases. Median nerve SNCV changes, despite the registered improvement were not statistically significant. Conclusions: With the intention to reduce the swelling of median nerve, Dexamethasone iontophoresis could be used as a modality of conservative treatment in CTS. ARP10 LONG-TERM EFFECTIVENESS OF PHYSICAL THERAPY MODALITIES IN CARPAL TUNNEL SYNDROME Baklaci K

ARP11 DECT IMAGING REVEALS NOVEL FINDING OF EXTENSIVE URATE DEPOSITION IN COSTAL CARTILAGES AND INTERVERTEBRAL DISCS IN PATIENTS WITH TOPHACEOUS GOUT AND AGE-MATCHED CONTROLS Carr A, Doyle A, Dalbeth N, Aati O, McQueen F University of Auckland, New Zealand Aim: To investigate monosodium urate (MSU) deposition in extraarticular sites within the abdomen in patients with tophaceous gout using dual energy computed tomography (DECT) scanning. Methods: 20 patients with tophaceous gout and 10 age and sex-matched controls plus one 15 year-old male control were enrolled. Patients were assessed for disease activity and serum creatinine and urate levels. DECT scans were obtained of the abdomen in all, centred on the kidneys. A dual x-ray tube 128-detector-row scanner (Siemens) was used; Tube A was operated at 100kV/260 mAs, tube B at 140 kV/130 mAs. Reconstructions used bone and soft tissue algorithms, 512 matrix, 0.75-mm slices with 0.5-mm increment. MSU deposition was quantified volumetrically using standardised software, separately by 2 readers, at the costal cartilages (CCs) and intervertebral discs (IVDs). Results: The median duration of gout was 17.5.years, tophus count 2, swollen/tender joint counts 0/0, CRP 2 mg/L, creatinine 101.5 umol/L (60– 105), and serum urate was 0.35 mmol/L (0.2–0.42).There was no evidence of MSU deposition in the kidneys in any of the patients or controls. However, there was extensive non-artefactual deposition of MSU in CCs and IVDs in patients and controls. Inter-rater reliability was very high at 0.99 for CC and 0.97 for IVD volumes; median (range) CC and IVD MSU volumes were 3.3 (0.07–11.6) and 0.5 (0.03–1.24) cm3 respectively and did not differ between patients and controls (p > 0.1). MSU volumes did not correlate with uric acid levels. No MSU deposits were present in IVDs of the 15 year-old male; further young controls are being recruited. Conclusions: We report a new finding of extensive asymptomatic MSU deposition in CCs and IVDs on DECT imaging in patients with tophaceous gout and in age-matched controls. This suggests that MSU deposition is common and physiological in the axial skeleton of older men.

Turkish Armed Forces Health Corps, Turkey Aim: This prospective, randomized, plasebo controlled clinical study aimed to investigate the effects of splinting, placebo (sham) physical therapy and real physical therapy combined with dexamethasone iontophoresis, therapeutic ultrasound and paraffin bath on electroneurophysiological and clinical parameters in carpal tunnel syndrome. Methods: 80 patients (78 female, 2 male) with CTS were included in the study.Patients were randomly assigned to physical therapy (n = 21), splinting (n = 22), physical therapy + splinting (n = 18) and placebo (sham) physical therapy (n = 19) groups. Steroid iontophoresis using dexamethasone as a conductive agent (500 g/mol, 2.5–4 mA), continuous ultrasound at 2.0 W/cm2 (3 MHz, 4 cm2 probe area), paraffin bath for hands was applied to the physical therapy group for fifteen sessions. Lightweight, neutralpositioned wrist splint was applied to the second group for one month (24 hours a day). Both physical therapy and splinting were applied to the third group in the same way and duration of first and second groups. Placebo (sham) ultrasound and placebo (sham) iontophoresis without steroid (both without energy emission) were applied to the sham therapy group. Evaluations were performed before, after the treatment and at first, third and sixth months. On the each evaluation session; electroneurophysiological parameters (distal motor latency, motor amplitude, sensory nerve conduction velocity, sensory peak latency and sensory amplitude of median nerve) and Boston Scale were assessed. Results: At the end of the study, mSNCV, mMDL and motor amplitude of splinting group were significantly improved (P < 0.05). Statistically significant improvement in mSNCV, mMDL and mSDL variables were found in physical therapy group (P < 0.05). mSNCV, mMDL and Boston symptom severity score variables of physical therapy plus splinting group were significantly improved (P < 0.05).

12


Abstracts

ARP12 GOUT PREVALENCE AND QUALITY OF CARE IN AN AUSTRALIAN GENERAL PRACTICE POPULATION Robinson P1, Taylor W2, Dalbeth N3 1 Centre for Neurogenetics and Statistical Genomics, Qld Brain Institute, University of Queensland, Brisbane, Australia 2 Department of Medicine, University of Otago, Wellington, New Zealand 3 Bone and Joint Research Group, University of Auckland, Auckland, New Zealand

Aim: Gout is a common and treatable form of arthritis.The central strategy for effective gout management is long-term urate-lowering therapy to main the serum urate at a target below 0.36 mmol/L.We sought to determine the prevalence of gout and quality of care in an Australian general practice population. Methods: Data was sourced from general practice point of care electronic records across Australia over a 5-year period (n = 1,479,449). Information was collected on patients with gout according to a validated definition. All patients who visited the same general practices over the study period formed the denominator group. The estimated prevalence of gout, the frequency of allopurinol prescription, and serum urate testing, and the percentage of patients achieving a serum urate target 65 years). At least one prescription for allopurinol was given to 57% of patients with gout during the five years of the study. Only 55% of patients with gout had serum urate tested at any time during the five years study period. A target serum urate concentration of 2000 IU/ml (nepholometry) could not be adequately blocked without compromising immunoassay measurement. After excluding patients with very high RF, many within-plate ICCs were >0.95, between run/within technician ICCs >0.85 and between plate longitudinal change scores ICCs >0.9. Serum with high RF needed higher concentrations of blocking agents than recommended in the literature. Some blocking agents, removed RF but the agent interfered with the immunoassay. Some blocking agent concentrations caused a high dose hook effect. Spike/recovery experiments showed that addition of RF factor increased many cytokine levels. Longitudinal serum mixing studies demonstrated satisfactory accuracy. Conclusions: These analytical studies demonstrate that MBIA are sufficiently robust for longitudinal evaluation of cytokine profiles in most patients with rheumatoid arthritis using selected blocking agents in pre-selected concentrations. Care must be taken with MBIA even when using these blocking agents in appropriate concentrations in serum with very high RF. ARP58 SAFETY AND EFFICACY OF BARICITINIB THROUGH 128 WEEKS IN AN OPEN-LABEL, LONG-TERM EXTENSION STUDY IN PATIENTS WITH RHEUMATOID ARTHRITIS Keystone E1, Taylor P2, Genovese M3, Schlichting D4, De La Torre I4, Beattie S4, Rooney T4, Suters A5 1

University of Toronto, Toronto, Canada 2 University of Oxford, Oxford, UK 3 Stanford University Medical Center, Palo Alto, USA 4 Eli Lilly Company, Indianapolis, USA 5 Eli Lilly Australia Pty Limited, Sidney, Australia

(96%) were treated and 133 (92%) completed an additional 52 wks.TEAE, SAE, and infection rates were slightly lower in Part D than in Part C. No opportunistic infections, tuberculosis, or lymphomas were observed through 128 wks. One fatal myocardial infarction occurred in the 8 mg group in Part C. Conclusions: Among pts completing 128 wks of a phase 2b study, clinical improvements observed at Wk 24 were maintained through Wk 128. Safety data collected during the OLE were consistent with previous baricitinib findings. ARP59 COMPARISON OF RHEUMATOID ARTHRITIS PATIENTS IN 3 ETHNIC GROUPS INVOLVING ENDOTHELIAL DYSFUNCTION AND TNF-α LEVELS Mohd Shahrir MS1, Asrul Abdul Wahab2, Kek Xin Yi1, Mohamad Norazrin Mohd Abas1, Siti Amira Kamarul Abdul Wahid1, Faridah Hanun bt Othman1 1

Department of Medicine, Faculty of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Jalan Yacoob Latif, 56000, Kuala Lumpur, Malaysia 2 Department of Pathology Faculty of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia, Jalan Yacoob Latif, 56000, Kuala Lumpur, Malaysia

Background and aims: Rheumatoid arthritis (RA) is a chronic destructive inflammatory disease which is associated with accelerated arteriosclerosis process that increases cardiovascular morbidity and mortality.This study is to determine the correlation between endothelial dysfunction using Carotid Intima MediaThickness (CIMT) measurement andTumour Necrotic Factor-α (TNF-α) levels between 3 ethnic groups which are Malay, Chinese and Indian. Materials and methods: A cross sectional study was done in 15 RA female patients from 3 different ethnic groups who free from cardiovascular (CV) risk factors. Patients were assessed using DAS28 for disease activity and Health Assessment Questionnaire (HAQ) for Standard Disability Index (SDI) before blood taking for TNF-α level and performing carotid ultrasonography for CIMT measurement. Results: Patients mean age was 51.9 ± 13.5 years and the mean disease duration was 7.1 ± 5.1 years. Among the patients, there were no thickened CIMT (>75th percentile matched for age and sex from the ‘Carotid Atherosclerosis Progression Study’). On multivariate analysis using KruskalWallisTest, factors such as duration of disease,TNF-α level, CIMT, DAS28C-Reactive Protein (CRP), DAS28 –Erythrocyte Sedimentation Rate (ESR) and SDI were not statistically significant associated with ethnic groups (p > 0.05). Furthermore, on Pearson correlation, there was no correlation of betweenTNF-α level and endothelial dysfunction among RA patients (p > 0.05). There was also no significant association between TNF- α level and CIMT with factors such as duration of disease, DAS – 28 CRP and SDI among RA patients. The non-significant association between any groups and dependent variables could be due limitation of sample sizes. Conclusion: In this study, there is no correlation between endothelial dysfunction and TNF α levels among 3 ethnic groups. Hence, there might be other risk factor that leads to CV diseases among RA patients.

Aim: Safety and efficacy findings of baricitinib (an oral JAK1/JAK2 inhibitor) treatment in RA patients (pts) to 128 wks are reported. Methods: Pts completing 24 wks of randomized and blinded treatment with 2, 4, or 8 mg baricitinib QD or 12 wks of randomized and blinded treatment with placebo or 1 mg baricitinib QD followed by 12 wks with 4 mg QD or 2 mg BID. Pts completing Part B entered a 52 wk open-label extension (OLE; Wks24-76, Part C), where pts received 4 or 8 mg QD. Pts completing Part C were eligible to enter 52 wk OLE (Wks 76-128, Part D) with 4 mg QD. Results: Of 204 pts at sites participating in Part C, 201 (99%) were treated and 169 (84%) completed 52 wks. Among those treated throughout with 4 mg (N = 108),TEAEs occurred in 63%, SAEs in 16%, infections in 35%, and serious infections in 5%. Among those receiving 8 mg at any time (N = 93), TEAEs occurred in 68%, SAEs in 13%, infections in 40%, and serious infections in 3%. Of 150 pts at sites participating in Part D, 144

26


Abstracts

ARP60 PREVALENCE, LONGEVITY AND SAFETY OF bDMARD TREATMENT FOR RHEUMATOID ARTHRITIS IN THE WESTERN REGION OF MELBOURNE

ARP62 EVALUATING FATIGUE IN RHEUMATOID ARTHRITIS PATIENTS ON BIOLOGIC THERAPY USING THE FUNCTIONAL ASSESSMENT OF CHRONIC ILLNESS THERAPY FATIGUE SCALE (FACIT-F)

Lim K, Jiang M

Paterson R1, Borissiouk I1, Griffiths H2, Wood N2, Holliday S2, Gibb L2, Crowley T3, Strickland G2

Western Health, Victoria

1

Aim: To evaluate the prevalence of bDMARD (biologic disease modifying anti-rheumatic drug) use in patients with rheumatoid arthritis in a public rheumatology clinic, and assess the treatment longevity and safety of bDMARD use in this population. Methods: Observational retrospective cohort study of public rheumatology outpatients at Western Health with rheumatoid arthritis who had used bDMARDs in the period between January 2011 to July 2014. A total of 2286 individual outpatient episodes were reviewed for a diagnosis of rheumatoid arthritis and of this group of patients, further review of records was performed to look for the use of bDMARDs and other characteristics i.e. duration of treatment, change in treatment and adverse events. Results: 27 out of 184 patients with rheumatoid arthritis had been treated with bDMARDs during the study period, giving a prevalence of 14.6%. Mean age of patients was 53, with a female: male ratio of 26:1. Average longevity of bMARD use during the study period was 13.4 months ± 11.4 (range 1–48 months). 7 patients (26%) required a change in their management (ceased in 3 out of 7). For patients requiring change in management, the average longevity was 14.8 months ± 10.31 (range 3–32 months).There were no serious adverse events related to bMARDs. Conclusions: The prevalence of bMARDs in patients with rheumatoid arthritis was 14.6% with an average longevity of greater than one year. About one quarter of patients required a change in management while on bDMARDs, with no serious adverse events reported. This data suggests that bMARD use in our population has been a safe and effective treatment option for patients with rheumatoid arthritis. ARP61 DO PATIENTS RESIDING IN RURAL AREAS REPORT LESS PAIN? A COMPARATIVE, CROSS SECTIONAL ANALYSIS OF AUSTRALIAN PATIENTS WITH RHEUMATOID ARTHRITIS RESIDING IN RURAL VERSUS METROPOLITAN AREAS OF NSW

Barwon Health Geelong University Hospital, Geelong, Victoria Barwon Rheumatology Service, Geelong, Victoria 3 School of Medicine, Faculty of Health, and Molecular and Medical SRC, Deakin University, Victoria 2

Aim: Fatigue is a debilitating, yet poorly understood symptom affecting patients with Rheumatoid Arthritis (RA). At Barwon Rheumatology, our impression has been that fatigue tends to improve with the commencement of biologic therapy, but this has never been objectively measured in our cohort of patients.This study aims to assess whether fatigue in patients with RA improves after 12 weeks of biologic therapy. Methods: The FACIT-F is a 13-item questionnaire evaluating fatigue, with higher summary scores indicative of less fatigue (scored 0–52). Twenty-two patients with RA (13 female, mean age 53, mean disease duration 9.2 years) completed the FACIT-F and Health Assessment Questionnaire disability index (HAQ-DI) questionnaires at baseline and after 12 weeks of biologic therapy. The HAQ-DI is scored out of 3, with lower scores indicating less disability. Clinical measures of disease activity and patient demographics were also recorded. Results: All patients demonstrated significant baseline to week 12 improvements in their mean FACIT-F (29 vs.37, p = 0.016), HAQ-DI (1.19 vs. 0.74, p = 0.019), ESR (24.2 vs. 11.4, p = 0.005), CRP (17.7 vs. 6.08, p = 0.004) and DAS-28-ESR (5.07 vs. 3.04, p = 0.0004). There was a moderate correlation between the FACIT-F score and measures of disease activity at baseline and week 12 including the ESR (r = −0.47, p = 0.27 at baseline and r = −0.57, p = 0.05 week 12) and DAS-ESR (r = −0.45, p = 0.03 at baseline and r = −0.60, p = 0.03 week 12). Disability assessed using the HAQ-DI strongly correlated with levels of fatigue (r = −0.59, p = 0.004 at baseline and r = −0.65, p = 0.001 week 12). In contrast, no association was found between the FACIT-F score and either age, disease duration or type of biologic therapy.

Royal Prince Alfred Hospital, NSW

Conclusions: The burden of fatigue at baseline in our study was similar to that reported in previous RA studies. Biologic therapy significantly improved levels of fatigue, physical functioning and disease activity after only 12 weeks of treatment.

Aim: Despite significant advances in treatments over the past few decades, pain management remains a significant issue for many patients with rheumatoid arthritis (RA). 1 On some measures of health, residents of rural areas fare worse than those in urbanised areas. 3 International evidence suggests there is a higher prevalence of pain in patients residing in rural areas compared to their metropolitan counterparts. 4 Few studies have evaluated this in Australian patients with RA.

ARP63 DEDUCE (DEFINING RHEUMATOID ARTHRITIS PROGRESSION USING DOPPLER ULTRASOUND IN CLINICAL PRACTICE): THE USE OF DOPPLER ULTRASOUND (DUS) IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA) IMPROVES PATIENT UNDERSTANDING OF DISEASE AND ADHERENCE TO TREATMENT

Honey A, Bleasel J, Richards B, Fowler D

Aim: To compare the prevalence and severity of residual pain in patients with well controlled RA, and to assess for any geographical variability. Methods: We performed a cross sectional analysis of 128 consecutive adult outpatients with RA who presented for review at a metropolitan (Royal Prince Alfred Hospital) or rural centre (Wagga Wagga). A paper-based anonymous questionnaire evaluating demographics, pain intensity and management and HRQOL (SF-36) was administered. Disease activity was assessed using DAS-28 ESR/CRP (complete remission ≤2.6, low disease activity ≤3.2).The postcode of usual residence was used to allocate a Rural, Remote and Metropolitan Areas (RRMA) score. Results: 111 patients (54 metropolitan and 57 rural) completed the questionnaire. 88% of all patients reported some level of pain (mean 45.3 mm (range 0–100 mm). 63% metropolitan patients and 74% rural patients had low disease activity.The prevalence of pain in those with complete remission and low disease activity was 80% (mean 33.5 mm) and 83% (mean 30.5 mm) respectively. For patients in complete remission, metropolitan patients reported a mean pain score of 23 mm, versus 36 mm in rural patients (p = 0.068). Conclusions: The prevalence of moderate levels of pain in patients with well controlled RA remains high. There was no significant geographical variation in the magnitude of pain reported, although there was a trend towards those living in rural areas reporting high levels of pain.


Joshua F1, Wong P2, Romas E3, Marabani M4, White R5, Bailey C6 1

Prince of Wales Hospital, Sydney, NSW Mid-North Coast Arthritis Clinic UNSW Rural Clinical School, Coffs Harbour, NSW 3 Department of Medicine, University of Melbourne, Melbourne, Victoria 4 Private Rheumatology Practice, Campsie, NSW 5 Private Rheumatology Practice, Campbelltown, NSW 6 Abbvie Australia, Sydney, NSW 2

Aim: To determine current use of DUS by rheumatologists and to assess the value of a DUS assessment tool for RA patients in clinical remission. Methods: Australian rheumatologists were invited to take part in the DEDUCE Medical Practice Activity that involved enrolling 4–6 RA patients aged ≥18 years in DAS28 remission. Rheumatologists and patients completed a preactivity survey assessing experience of DUS prior to DUS evaluation using the US7 score. Rheumatologists discussed results with patients using specifically developed visual aids. Patients and rheumatologists then completed post-activity questionnaires. Results: Eighty patients recruited by 21 rheumatologists completed preactivity questionnaires. Patients who had previously undergone DUS found DUS improved their understanding of RA (18/19, 95%) and the likelihood of medication adherence (16/19, 84%). Fifteen of the 21 rheumatologists had previously used DUS. 10/15 (67%) used DUS in patients in clinical

27

Abstracts

remission and low disease activity. 12/15 (80%) and 9/15 (60%) agreed it aided patient communication and medication adherence, respectively. Sixtysix patients completed post-activity questionnaires. Of the 58 patients who had post-DUS discussions with their rheumatologist, 51 (88%) reported that these discussions improved understanding of their disease and 55 (95%) believed that it will help them to take medications as prescribed. 50 of the 61 (82%) patients whose discussions utilised the visual aids found them useful. Overall, 56/66 (85%) of patients agreed that DUS imaging is a useful tool in assessing disease activity. Post-activity, 20/21 (95%) rheumatologists felt they would use DUS to guide therapeutic decisions and 16/21 (76%) found the visual aids useful for patient communication. 13/21 (62%) thought DUS would aid patient medication adherence. Conclusions: Almost all rheumatologists and patients who experienced DUS felt that DUS was a useful tool. Communication of the results using visual aids enabled patients to better understand their disease and take medications as instructed. ARP64 PATTERNS OF TOCILIZUMAB USE AND SAFETY IN PATIENTS WITH RHEUMATOID ARTHRITIS: INTERIM RESULTS FROM A MULTINATIONAL OBSERVATIONAL STUDY (ENCORE PRESENTATION) Haraoui B1, Casado G2, Theander E3, Czirjã¡k L4, Taylor A5, Button P6, Hinsch Gylvin L7, Caporali R8 1

Department of Medicine, Centre Hospitalier De L’université De Montréal, Montréal, QC, Canada 2 Hospital Militar Central, Buenos Aires, Argentina 3 University Hospital Malmö, Lund University, Malmö, Sweden 4 University of Pécs, Pécs, Hungary 5 Royal Perth Hospital, Perth, Australia 6 Roche Products Pty Limited, Dee Why, Australia 7 F. Hoffmann-La Roche, Basel, Switzerland 8 Division of Rheumatology, University of Pavia, Irccs Policlinico San Matteo, Pavia, Italy Aim: To report interim observations of patterns of tocilizumab (TCZ) use, adherence to label recommendations, and safety from the ACT-UP study. Methods: ACT-UP is an umbrella project; data is pooled from several international, observational, post-marketing studies investigating intravenous TCZ use in patients with RA in routine care. Adult patients with moderate to severe RA who started TCZ within 8-weeks of enrolment were observed for 6-months. Dosing regimens, interventional procedures, clinic visits, and laboratory analyses were at investigator’s discretion. Results: Of 961 patients who received their first TCZ dose by June-302013, 352 (37%) started monotherapy (Mono) and 609 (63%) started combination DMARDs (Combo); 94% Mono and 95% Combo patients started TCZ at 8 mg/kg. At 6-months 72%-mono and 84%-combo patients continued to receive 8 mg/kg TCZ.TCZ dose changes were reported for 34 (10%) Mono patients (7-increased, 11-decreased, 16 both increased and decreased) and 66 (11%) Combo patients (11-increased, 20-decreased, 35 both increased and decreased). Reasons for dose changes were adverse events (AEs) (3.7%-Mono; 4.9%-Combo) and lack of efficacy (1.7%Mono; 0.5%-Combo). Median methotrexate dose for Combo patients was 15 mg/wk. Sixty-four patients changed methotrexate dose during the study (median dose change:-5 mg/week).Twenty-eight (8.0%) patients who started TCZ Mono added a DMARD during the study. Baseline corticosteroids were used by 46%-Mono and 57%-Combo patients. TCZ therapy was discontinued in 97 (27.6%) Mono and 97 (15.9%) Combo patients. Reasons for discontinuations included lack of efficacy (11%-Mono; 27%-Combo), AEs (27%-Mono; 29%-Combo), and other (62%-Mono; 44%-Combo). AEs occurred in 53% of patients in each group. Infections were less common in Mono than Combo patients. Conclusions: In this multinational observational study, 37% of patients started monotherapy TCZ. TCZ was well tolerated both as monotherapy and combination therapy. # Haraoui B, et al. Arthritis and Rheumatology 2014;66(11):S226. Copyright©2014 ACR, Atlanta, GA. ‘This material is reproduced with permission of John Wiley & Sons, Inc.’

28

ARP65 CANCER-RELATED INCIDENCE (SIR), CANCER-RELATED MORTALITY (SMR) AND THEIR PREDICTORS: 20 YEAR FOLLOW-UP OF THE SYDNEY RHEUMATOID ARTHRITIS LONGITUDINAL OBSERVATIONAL STUDY (SRALOS) Lassere M1, Portek I2, Sturgess A1, Edmonds J3 1

St George Hospital, University of NSW Combined Rheumatology Practice, St George Hospital 3 University of NSW 2

Aim: The primary objective of this study is to report cancer-related standardised incidence ratio (SIR), cancer-related standardised mortality ratio (SMR) and their predictors in the Sydney Rheumatoid Arthritis Longitudinal Observational Study (SRALOS). Methods: Study population was all RA patients seen at a teaching hospital rheumatology clinic and four private practices between 1/1/1990 and 31/12/ 1994. Clinical, pathology, imaging and patient-reported outcome data collection occurred in 1991, 1992–1993, 1995, 2002 and 2004. In 2014 record linkage with Australian National Death Index was performed to determine fact of death until end 2013 and cause of death to end of 2012. Record linkage with the NSW Central Cancer Registry performed in 2005 and 2008 determined cancer incidence (except non-melanotic skin cancers) with ICD-10-AM Topography and ICD3 Morphology Codes (histology). All-cause and cause-specific cancer SIRs, cancer-specific SMRs and predictors were evaluated using survival analysis. Results: The 608 subjects with RA had median disease duration of 7 years at cohort entry. SIR for any cancer was 1.2 (95% CI 1.0, 1.5), in males SIR 1.34 (1.01, 1.8), females SIR 1.1 (0.88, 1.4). Cancer specific SIRs: melanoma 1.12 (0.55, 2.23): ever on methotrexate (MTX) 1.6 (0.7, 3.3), never MTX 0.63 (0.09, 4.4). Lymphoma 1.96 (0.9, 4.1), breast 0.78 (0.4, 1.4); lung 1.1 (0.6, 2.0): MTX ever 0.55 (0.2, 1.7), MTX never 3.3 (1.7, 6.6). All-cause mortality SMR was 1.7 (95% CI 1.6, 1.9). All-cause cancer SMR was 1.5 (1.2, 1.9): ever MTX 1.2 (0.9, 1.6), never MTX 1.9 (1.3, 2.8). Cancer specific mortality for lymphoma SMR 3.3(1.6, 6.6): ever MTX 2.1 (0.7, 6.5), never MTX 5.4 (1.7, 16.6), lung 1.6 (1.0, 2.6): males 1.9 (1.1, 3.4); ever MTX 0.9 (0.4, 2.0), never MTX 4.8 (2.8, 8.2), melanoma, breast and prostate no signal. Conclusions: In an RA cohort established in the early 1990s, all-cancer specific mortality was increased. Although the most frequent cancers were breast and prostate, after adjusting for age and gender there was an excess of deaths from lung cancer and lymphoma. Methotrexate was protective. Reasons for these findings are explored and implications discussed. ARP66 INCREASES IN SERUM CHOLESTEROL WITH BARICITINIB TREATMENT ARE ASSOCIATED WITH FAVORABLE CHANGES IN APOLIPOPROTEIN CONTENT AND WITH IMPROVEMENT IN DAS28-CRP IN PATIENTS WITH RHEUMATOID ARTHRITIS Kremer J1, Genovese M2, Keystone E3, Taylor P4, Zuckerman S5, Schlichting D5, Nantz E5, Beattie S5, MacIas W5, Suters A6 1

Albany Medical College, Albany, USA Stanford University Medical Center, Palo Alto, USA 3 University of Toronto, Toronto, Canada 4 University of Oxford, Oxford, UK 5 Eli Lilly Company, Indianapolis, USA 6 Eli Lilly Australia Pty Limited, Sydney, Australia 2

Aim: Treatment with baricitinib, an oral JAK1/JAK2 inhibitor, demonstrated improvements in signs and symptoms of RA through 52 wks in a Phase 2b study* and also in dose- and time-dependent changes in serum lipids, LDL particle size, and HDL and VLDL particle numbers**. Methods: Patients (pts) with RA were randomized to QD blinded treatment with placebo (PBO) (n = 98) or baricitinib 1 mg (n = 49), 2 mg (n = 52), 4 mg (n = 52), or 8 mg (n = 50) for 12 wks. Apolipoprotein content was assessed at Wks 4/12 for PBO and 4-/8-mg baricitinib groups. Results: Pts who continued treatment with baricitinib through 52 wks maintained stable cholesterol and triglyceride profiles with no further changes beyond Wks 12/24. Increases in apolipoprotein A-I, apolipoprotein B, and total apolipoprotein CIII through 12 wks were observed with 4-/8-mg baricitinib with no increase in LDL-associated apolipoprotein CIII. Baricitinib treatment also demonstrated a reduction in HDL-associated SAA at 4-/8-mg doses while a reduction in Lp(a) was observed only with 8-mg baricitinib © 2015 The Authors Internal Medicine Journal © 2015 Royal Australasian College of Physicians Internal Medicine Journal (2015) 45 (Suppl. 2): 1–46

Abstracts

(all p < 0.05).These apolipoprotein changes coincided with the increases in serum lipids apparent by Wk 4. In pts treated across all doses of baricitinib, change in HDL cholesterol correlated with absolute DAS28-CRP score at Wk 12 (r = −0.32, p < 0.001) and the change from baseline to Wk 12 in DAS28-CRP (r = −0.28, p < 0.001). Specifically, pts achieving DAS28CRP 3 times the upper limit of normal on two or more blood tests, while 55% indicated that they would just stop leflunomide. Conclusions: Choice of initial dosing of leflunomide among responding rheumatologists varied substantially, although the loading dose initially recommended has fallen out of favour. Given the variable pharmacokinetics of leflunomide, alternate daily dosing is a rational option, used by 70% of rheumatologists. Future research should focus on establishing whether this dosing schedule has any observable benefit. The use of cholestyramine washout for hepatic toxicity is not universal, despite being recommended by clinical guidelines. RHPA-P9 A SYSTEMATIC EVALUATION OF SINGLE MEASURES IN DISCRIMINATING CHANGES IN RHEUMATOID ARTHRITIS DISEASE ACTIVITY Wojciechowski J1, Wiese M2, Proudman S3, Foster D1, Upton R1 1

Australian Centre for Pharmacometrics, School of Pharmacy and Medical Sciences, University of South Australia, SA 2 Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, SA 3 Rheumatology Unit, Royal Adelaide Hospital. Discipline of Medicine, University of Adelaide, SA Aim:The treat-to-target approach in the management of rheumatoid arthritis (RA) involves frequent assessments of disease activity to guide drug dose and regimen adjustments until a pre-defined low disease activity state and/or remission has been achieved. As a single or composite measure that best reflects a change in disease activity in response to treat-to-target therapy (or lack thereof) is yet to be identified, a systematic evaluation of single RA measures on their ability to do so using population-modelling methods was conducted. Methods: A total of 11 single measures of RA disease activity (tender and swollen joint counts, acute phase reactants, and global health, pain and physical function assessments) were obtained from patients with recent-

46

onset RA who attended the Royal Adelaide Hospital. Participants received combination disease-modifying anti-rheumatic drugs (DMARDs) according to a treat-to-target approach with pre-defined triggers for treatment intensification. Models for each measure describing the magnitude and variability of score change from baseline to a single ‘treated’ state (follow-up clinic visit at approximately 2-years) in the population were developed using NONMEM®. Measures that displayed a large change between states with minimal variability in the population were ranked highly in their discriminatory capacity. Results: A total of 203 patients over a follow-up of 1.8 ± 0.37 years were included. Physician’s assessment of the patient’s global health and swollen joint counts demonstrated a greater ability to discriminate changes in RA disease activity than others. Limited joint counts (both tender and swollen 28-joint counts) were no less sensitive to change than comprehensive joint counts. Non-specific markers of inflammation such as ESR and CRP were less discriminatory. Conclusions: Population-modelling methods had not previously been applied to evaluating the discriminatory capacity of single RA disease activity measures. This is the first step in establishing and evaluating the best composite index for the treat-to-target approach. RHP-P10 UNUSUAL POSTOPERATIVE PELVIC FLOOR DYSFUNCTION IN PATIENTS WITH SJÖGREN’S SYNDROME: A CASE SERIES OVER 7 YEARS IN A REGIONAL REFERRAL UNIT Budden A1, Sturgess A2, Moore K3 1

Gynaecology Department, Royal Hospital for Women, UNSW Rheumatology Department, St George Hospital, UNSW 3 Pelvic Floor Unit, St George Hospital, UNSW, NSW 2

Aim: Autoantibodies against the muscarinic M3 receptor may cause salivary underproduction in patients with Sjögren’s Syndrome (SS), as well as parasympathetic and detrusor muscle dysfunction. We aim to investigate whether women with SS are more likely to have post-operative voiding dysfunction, vaginal stenosis, poor response to anticholinergic medication, or all of the above compared to the general population. Methods: Patients presenting with pelvic floor dysfunction, who were known to have a diagnosis of Sjögren’s Syndrome, were prospectively recorded since 2007. Patient notes were searched for presenting complaint, abnormal pelvic examination findings including vaginal fibrosis, pelvic surgery and subsequent surgical complications, voiding dysfunction, and response to anticholinergic medication. Results: 2688 new women with pelvic floor dysfunction were seen between 2007 and 2014 with 13 SS patients (0.5%) identified. All presented with symptoms of incontinence or voiding dysfunction with five also complaining of pelvic organ prolapse. In 7 patients with no previous surgery, mild fibrosis was observed after vaginal ring use in one. Of 6 women who underwent previous surgery, severe fibrosis was observed in 4 including 3 where a speculum could not be passed and another who could not pass urine due to retropubic fibrosis, and moderate fibrosis occurred in 2 others. Post-operative voiding dysfunction affected 6 of 9 women (10–15% in the general population). Anticholinergic medication was not tolerated by 7 of 10 women, despite the use of newer anticholinergics. Of the 13 patients, only one patient was unaffected by fibrosis, voiding dysfunction, or anticholinergics intolerance however she never underwent operation. Conclusions: This case series demonstrates a substantial risk of vaginal stenosis or vaginal tissue thickening, an increased likelihood of either postoperative voiding dysfunction or poor response to anticholinergic medication, or both, which occurred in 92% of women with Sjögren’s Syndrome in this case series.
