Servet Akar

The effect of antidrug antibodies on the sustainable efficacy of biologic therapies in rheumatoid arthritis: practical consequences

Biologic therapies, predominantly TNF-α inhibitors, have revolutionized the treatment of rheumatoid arthritis (RA). However, their clinical utility can be limited by the development of antidrug antibodies (ADAs). Immunogenicity is a complex phenomenon related to various drug, disease, and patient characteristics, and may be more common with the monoclonal antibodies than with etanercept, a soluble TNF receptor-Fc immunoglobulin fusion protein. Neutralizing antibodies – those that hinder bioactivity by preventing drug molecules from binding to TNF – are correlated with reduced serum drug concentrations, loss of therapeutic response, adverse events, and treatment discontinuation. Cost-effective use of these agents will depend on further research into drug and ADA assays, and how they should guide dose reduction or switching strategies.

Performance characteristics of the simplified version of ankylosing spondylitis disease activity score (SASDAS)

Various types of disease activity measures are available for axial spondyloarthritis (axSpA), and there is no gold standard for all individual patients. The ankylosing spondylitis disease activity score (ASDAS) is highly discriminatory, sensitive to change, and associated with structural progression. A simplified version of the ASDAS (SASDAS) was proposed and found to be a simple and practical tool to assess disease activity. Our aim was to test the performance characteristics of the SASDAS and compare it with validated tools. In total, 97 consecutive ankylosing spondylitis (AS) patients were included in the study. Disease activity was assessed by the ASDAS-erythrocyte sedimentation rate (ESR), ASDAS-C-reactive protein (CRP), bath ankylosing spondylitis disease activity index (BASDAI), and SASDAS. The relationship among these activity indices and the level of agreement of various activity categories were tested. There was a strong correlation between the SASDAS and other activity indices, including the BASDAI (ru2009=u20090.916, pu2009<u20090.001), ASDAS-CRP (ru2009=u20090.847, pu2009<u20090.001), and ASDAS-ESR (ru2009=u20090.942, pu2009<u20090.001). Although the agreement between the ASDAS-ESR and SASDAS was good (weighted kappa of 0.744 and total agreement of 77xa0%), there was moderate agreement between the ASDAS-CRP and SASDAS (weighted kappa of 0.579 and total agreement of 66xa0%). The disagreement was particularly striking in “moderate” and “high disease activity” states. Approximately 40xa0% of patients classified as moderate activity according to the ASDAS-ESR and 45xa0% according to the ASDAS-CRP were differentially categorized by the SASDAS. The results of the present analysis suggest that the simplified version of the ASDAS-ESR should be further validated in various settings and populations due to a questionable level of agreement between the ASDAS-CRP and SASDAS.

Do major histocompatibility complex tag single nucleotide polymorphisms accurately identify HLA-B27 in the Turkish population?

To evaluate the performance of human leukocyte antigen (HLA)‐B27 tag single nucleotide polymorphisms (SNPs) by polymerase chain reaction – restriction fragment length polymorphism (PCR–RFLP).

Role of the mTOR pathway in minor salivary gland changes in Sjogren’s syndrome and systemic sclerosis

BackgroundTo examine the activity of the mammalian target of rapamycin (mTOR) pathway and its regulators, transforming growth factor (TGF)-β1 and phosphatase and tensin homolog (PTEN), in minor salivary gland biopsies of Sjogren’s syndrome (SS) and systemic sclerosis (SSc) patients.MethodsWe retrospectively evaluated SS, SSc, and SS-SSc overlap patients admitted to our outpatient rheumatology clinic between January 2007 and December 2015 who underwent a minor salivary gland biopsy. Patient demographics and some clinical features were obtained from hospital records. Immunohistochemistry was used to analyze total mTOR, total PTEN, and TGF-β1 expression in the biopsied tissues. The biopsy specimens were also examined for the presence and degree of fibrosis.ResultsMinor salivary gland biopsies of 58 SS, 14 SSc, and 23 SS-SSc overlap patients were included in the study. There was no significant difference in mTOR expression between these groups (Pu2009=u20090.622). PTEN protein was expressed in 87.2% of patients with SS, 57.9% with overlap syndrome, and 100% of the SSC patients, and these differences were statistically different (Pu2009=u20090.023). Although ductal epithelial TGF-β1 expression was similar between the groups (Pu2009=u20090.345), acinar cell expression was found to be more frequent in the SSc (72.7%) and overlap patients (85.7%) in comparison with the SS cases (58.2%; Pu2009=u20090.004).ConclusionmTOR may be one of the common pathways in the pathology of both SS and SSc. Hence, there may be a role for mTOR inhibitors in the treatment of both diseases. Additionally, PTEN and TGF-β1 expression may be a distinctive feature of SSc.

Evaluation of periostin and factors associated with new bone formation in ankylosing spondylitis: Periostin may be associated with the Wnt pathway

Periostin has been shown to be involved in bone anabolism through the regulation of Wnt‐β‐catenin signaling. It may be one of the pathogenic mechanisms in syndesmophyte formation in ankylosing spondylitis (AS). The aim of this study was to evaluate serum periostin levels in patients with AS and to assess relationships among biomarkers of bone formation and periostin in disease outcomes, particularly radiographic changes.

Choroidal and central foveal thickness in patients with scleroderma and its systemic associations

The aim was to investigate the morphological changes in the fovea and choroid in patients with scleroderma and its systemic associations.

SAT0395 Similarities and differences between non-radiographic and radiographic axial spondyloarthritis in proof cohort

Background Previously, some differences between non-radiographic and radiographic axial spondyloarthritis (axSpA) – such as a higher prevalence of females and lower level of acute phase reactants in non-radiographic axSpA (nr-axSpA) – have been reported in national observational studies, mostly from Europe. Objectives To compare demographic and clinical characteristics of patients (pts) with nr-axSpA and radiographic axSpA (ankylosing spondylitis, AS) in a large multinational cohort of pts with recently diagnosed axSpA. Methods PROOF is a prospective observational study evaluating clinical and radiographic outcomes in axSpA pts in rheumatology clinical practice in 29 countries. Pts with axSpA fulfilling ASAS classification criteria were eligible if diagnosed ≤1 year prior to study enrolment. Investigators confidence with the diagnosis of axSpA was ascertained on a numeric rating scale (NRS 0–10) at enrolment and end of follow-up. At baseline, demographic and clinical data related to the diagnosis, disease activity, quality of life and work productivity, as well as conventional radiographs of the sacroiliac joints were collected. Classification as nr-axSpA or AS was based on the results of the assessment of sacroiliac radiographs. Available radiographs were assessed first by a local reader and then by a central reader according to the grading system of the modified New York criteria. In the case of a disagreement in the classification (nr- axSpA or AS), the radiograph was evaluated by the 2nd central reader, who was blinded to the previous assessments and the final classification was made based on the decision of 2 out of 3 readers. Results Of the 2126 pts enrolled in PROOF, 1281 (60.3%) pts were classified as AS and 845 (39.7%) as nr-axSpA according to investigators. The confidence with the diagnosis of axSpA was 8.7±1.8. The final classification according to the central assessment of sacroiliac radiographs was confirmed in1583 pts included in this analysis. A total of 987 pts (62.3%) were classified as AS and 596 (37.7%) as nr-axSpA. AS pts expectedly had longer symptom duration, more frequently had elevated and higher CRP and were more often male and treated with TNF inhibitors (Table). In addition, HLA-B27 positivity was more frequent among AS pts, while pts with nr-axSpA had a significantly higher prevalence of enthesitis, psoriasis, and inflammatory bowel disease (IBD). The prevalence of other SpA features was comparable between the two subgroups of axSpA. Mostly, pt-reported outcomes reflecting burden of disease were comparable between the two subgroups, but BASDAI was significantly higher in the nr-axSpA subgroup (Table). Conclusions There were a few differences between nr-axSpA and AS pts in the PROOF cohort. The clinical constellation of female sex, low CRP, enthesitis, psoriasis, and IBD in nr-axSpA pts appears to reflect a phenotype less prone to structural damage in the sacroiliac joints. However, the clinical burden of disease was comparable between the two subgroups of axSpA. Acknowledgements AbbVie funded the PROOF study, contributed to its design and participated in data collection, analysis and interpretation of the data, and in writing, review, and approval of the publication. Medical writing support was provided by Deepa Venkitaramani, PhD, of AbbVie. Disclosure of Interest D. Poddubnyy Grant/research support from: AbbVie, Janssen, MSD, Novartis, Pfizer, Consultant for: AbbVie, BMS, Boehringer, MSD, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, BMS, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, R. Inman Grant/research support from: AbbVie, Amgen, and Janssen, Consultant for: AbbVie, Amgen, Janssen, Lilly, Novartis, and Pfizer, J. Sieper Grant/research support from: AbbVie, Merck, and Pfizer, Consultant for: AbbVie, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Janssen, Merck, Novartis, Pfizer, Roche, and UCB, S. Akar Grant/research support from: AbbVie, BMS, MSD, Novartis, Pfizer, Roche, and UCB, Consultant for: AbbVie, BMS, MSD, Novartis, Pfizer, Roche, and UCB, Speakers bureau: AbbVie, BMS, MSD, Novartis, Pfizer, Roche, and UCB, S. Muñoz-Fernández Grant/research support from: Abbvie, BMS, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant for: Abbvie, BMS, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Speakers bureau: Abbvie, BMS, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, M. Hojnik Shareholder of: AbbVie, Employee of: AbbVie

THU0586 Agreement of Patient and Physician Global Assessment of Disease Activity in Adult Onset Still's Disease

Background There is not valid outcome measures for assessment Adult onset Stills disease (AOSD) activity. The patients or physicians global view is relevant way to assess this kind of complex diseases. However, it is well known that there is discordance between patient and physician perspective for disease activity in different inflammatory diseases. Objectives Objective of this study was to evaluate agreement of patient and physician perspective in AOSD patients. Methods We conducted a cross-sectional, multicenter study for assessment of disease activity in AOSD patients. All AOSD patients were fulfilled Yamaguchi criteria. For every center, at least 20% of AOSD patients had to be an active state according to physician assessment. Age, sex, disease duration, current disease symptoms was recorded. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leucocyte, and ferritin level also recorded. Visual analog scale (VAS) (0–10 cm) used for physician and patient global assessment of disease activity. Disease activity status were also assessed by likert scale (as remission, low, moderate, severe, and more severe disease activity) for both patients and physician perspective. Patient global assessment VAS and physician global assessment were correlated by correlation coefficient (r). Agreement of disease activity level for patient and physician perspective were calculated with kappa. Kappa >0.6 was accepted as significant. Results One hundred thirty (83, 63.4% female) AOSD patients were enrolled. Mean age was 38 (14) years old and median disease duration was 3 years (0–29). Currently AOSD symptoms followed; fever 34 (26.2%), rash 28 (21.5%), arthritis 31 (23.8%), arthralgia 60 (46.2%), sore throat 28 (21.5), myalgia 42 (32.3), lympadenopathy 12 (9.2%), splenomegaly 17 (13.1%), hepatomegaly 7 (5.4%), pleuritic 3 (2.3%), hemophagocytic syndrome 2 (1.5%). ESR 47.7%, CRP 43.8%, ferritin 27.0%, and leucocyte 43.1% were higher than upper limit. Mean patient global assessment VAS was 3.53 (3.25), and mean physician global assessment VAS was 2.71 (2.95). Correlation coefficient (r) of patient and physican global VAS was 0.89. There was excellent agreement according to severe/more severe disease activity at patient and physician level (kappa 0.88 (CI 95% 0.79–0.98). There was also good to excellent agreement according to low disease activity/remission at patient and physician level (kappa 0.74 (CI 95% 0.62–0.86). Conclusions Although, features of AOSD seems more complex with constitutional symptoms, joint or reticuloendothelial system involvement, patients and physicians assess level of disease activity similarly. We thought, this results will be helpful for procedure of new composite index in AOSD. Disclosure of Interest None declared

AB0678 A Comparison of Depression and Anxiety Levels in Patients with Non-Radiographic Axial Spondyloarthropathy with Those in Patients with Ankylosing Spondylitis: Table 1.

Background The concept of axial spondyloarthropathy (SpA) recently recommended by the ASAS includes patients comprising the early and late stages of the disease. This concept also includes patients not meeting the criteria for ankylosing spondylitis (AS) but classified as non-radiographic SpA on the basis of chronic lumbar back pain and other characteristics of SpA. Although this group is more heterogeneous and distinct from AS in terms of some characteristics, it still has a similar burden in terms of disease activity. Psychiatric symptoms can often be seen in patients during the course of AS. Depressive symptoms are seen at levels of 27.4–55.5% and anxiety symptoms at levels of 19.5–60.9%. Few studies have investigated this situation in the non-radiographic SpA group. Objectives To assess depression and anxiety levels in AS and non-radiographic SpA groups and to review potentially associated factors. Methods One hundred fifty-five (114 AS, 41 non-radiographic SpA) patients with axial SpA according to the ASAS definition were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess activity, visual anolog scale (VAS) for spinal pain, the Bath Ankylosing Spondylitis Functional Index (BASFI) for functional capacity and the Ankylosing Spondylitis Quality of Life (ASQOL) for quality of life. The State-Trait Anxiety inventory (STAI), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were used to determine psychiatric symptoms. Results The AS patient group (mean age 39±10.8, male 73.4%) was older than the non-radiographic SpA group (mean age 35±10.1, male 54.8%), and had a greater preponderance of males. No difference was determined between the two groups in terms of BASDAI, VAS spinal pain, ASQOL or BASFI scores. Psychiatric measurements were also similar between the AS and non-radiographic SpA groups. The STAI, BDI and BAI exhibited good correlated with BASDAI, BASFI, ASQOL and VAS spinal pain (Table).Table 1. Correlations between psychiatric symptoms and disease, functional capacity and quality of life scales BASDAI BASFI VAS spinal pain ASQOL STAI-I (state anxiety) r 0.432 0.343 0.373 0.481 p <0.001 <0.001 <0.001 <0.001 STAI-II (trait anxiety) r 0.375 0.342 0.234 0.420 p <0.001 <0.001 0.005 <0.001 Beck anxiety inventory r 0.430 0.375 0.326 0.508 p <0.001 <0.001 <0.001 <0.001 Beck depression inventory r 0.427 0.432 0.410 0.595 p <0.001 <0.001 <0.001 <0.001 Conclusions Despite the presence of some clinical differences between the AS group and the non-radiographic SpA group, regarded as the early stage of the disease, the two group exhibit similar features in terms of psychiatric symptoms and disease activity. Psychiatric symptoms are closely associated with disease activity, functional capacity and quality of life. Disclosure of Interest None declared

THU0407 Baseline Results from Proof – A 5-Year Observational Study of Long-Term Disease Outcome in Axial Spondyloarthritis

Background Axial spondyloarthritis (axSpA), encompassing ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) without advanced structural lesions in the sacroiliac joints (SIJ), is a relatively new disease concept. The natural disease course of axSpA, including progression of structural damage over time, has not yet been systematically studied in large patient (pt) groups. Objectives To report the baseline data of PROOF, a large study currently being conducted in 29 countries across the world, evaluating long-term outcomes in pts with axSpA classified by ASAS criteria. Methods PROOF is a multi-country prospective observational study evaluating axSpA pts in rheumatology clinical practice over 5 years. Pts with axSpA fulfilling ASAS classification criteria were eligible, if diagnosed ≤12 months prior to study enrolment. Investigators confidence with the diagnosis of axSpA is ascertained on a numeric rating scale (NRS 0–10) at enrolment and end of follow-up. Assessments of disease activity (BASDAI, ASDAS-CRP), physical function (BASFI), quality of life (SF-12v2), productivity (WPAI-SHP), and pelvic X-ray are scheduled at yearly follow-up visits. X-rays are graded according to NY criteria by local and central readers. Results 2084 pts with axSpA fulfilling ASAS criteria have been enrolled in PROOF study, 1259 pts with AS (60%) and 825 pts with nr-axSpA (40%) according to the investigators. The level of confidence with the diagnosis of axSpA was 8.7±1.8. The imaging criterion was fulfilled by 85% of pts (40% MRI, 51% X-ray, 9% both), 15% of pts were classified through the clinical arm. HLA-B27 was tested in 85% of pts and found to be positive in 68% of cases (70% with AS and 60% with nr-axSpA). Overall, pts were in their mid-thirties, had a long delay in referral to rheumatologist and recently diagnosed axSpA. Comparison of demographic and clinical characteristics between pts with AS and nr-axSpA is shown in Table 1. Pelvic x-rays were reportedly done in 1635 (78%) pts within 6 months of the baseline visit; to date both local and central readers have scored x-rays of 1344 pts (82% of available). Of the 1344 pts, 83.3% retained their classification (AS or nr-axSpA) after the central reading, while 16.7% were classified differently. Based on the kappa value, there was a substantial agreement on the grading of x-rays between the local and central readers: kappa=0.63 (95% CI, 0.59–0.68). Conclusions PROOF is the largest observational study in pts with axSpA classified by ASAS criteria so far. It provides insights into the clinical practice worldwide and aims to assess long-term outcomes of axSpA. Baseline results confirmed comparable clinical features and disease burden between AS and nr-axSpA, highlighted a long delay in referral to rheumatologists, and showed a good agreement between the SIJ x-ray grading by local and central readers. Acknowledgement AbbVie funded the PROOF study, contributed to its design and participated in data collection, analysis and interpretation of the data, and in writing, review, and approval of the publication. Medical writing support was provided by Deepa Venkitaramani, PhD, of AbbVie. Disclosure of Interest R. Inman Grant/research support from: AbbVie, Amgen, Janssen, Pfizer, and UCB, Consultant for: AbbVie, Amgen, Janssen, Pfizer, and UCB, Speakers bureau: AbbVie, Amgen, Janssen, Pfizer, and UCB, J. Sieper Grant/research support from: AbbVie, Merck, Pfizer, and UCB, Consultant for: AbbVie, Merck, Pfizer, and UCB, Speakers bureau: AbbVie, Merck, Pfizer, and UCB, D. Poddubnyy Grant/research support from: AbbVie, BMS, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant for: AbbVie, BMS, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Speakers bureau: AbbVie, BMS, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, S. Akar Grant/research support from: AbbVie, BMS, MSD, Novartis, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: AbbVie, BMS, MSD, Novartis, Pfizer, Roche and UCB, S. Munoz-Fernandez Grant/research support from: Abbvie, BMS, Janssen, MSD, Pfizer, Roche, and UCB, Consultant for: Abbvie, BMS, Janssen, MSD, Pfizer, Roche, and UCB, Speakers bureau: Abbvie, BMS, Janssen, MSD, Pfizer, Roche, and UCB, M. Hojnik Shareholder of: AbbVie, Employee of: AbbVie