F. Berghea

Extended report: Development of patient-centred standards of care for osteoarthritis in Europe: the eumusc.net-project

Objective The eumusc.net project is an initiative founded by the European Community and the European League Against Rheumatism. One aim of the project was to facilitate equal standards for musculoskeletal health across Europe. The aim of this work-package was to develop patient-centred and consensus based standards of care (SOC) for osteoarthritis (OA), which should be available in a professional and a patient version. Methods A systematic review concerning guidelines dealing with OA was conducted. Furthermore, experts in musculoskeletal diseases were contacted to ensure that ‘grey’ literature was not excluded. Documents that fulfilled predefined inclusion/exclusion criteria were included and all interventions for OA were extracted and categorised. Based on this list of interventions, a three round Delphi exercise with an international and multidisciplinary expert panel, including patient research partners, was performed to achieve expert consensus. Results Six documents were included and used for further analysis. Out of them, 46 interventions have been extracted and 10 consensus based SOC were formulated. In addition, a patient version, written in a lay-understandable wording and in the format of checklist questions was developed. An example is SOC 5: “People with OA should achieve optimal pain control using pharmacological and non-pharmacological means.” The matching patient-centred checklist question reads: “Do I know how to control pain associated with OA?” Conclusions The SOC for OA will be available in the 23 languages of the European Union to enhance unified information to patients and professionals and to further harmonise the treatment/care of OA within Europe.

Tenosynovitis US scoring systems follow synovitis and clinical scoring systems in RA and are responsive to change after biologic therapy.

AIMS To investigate by ultrasonography (US) in a cohort of active RA patients starting biologic therapy the responsiveness of tenosynovitis of wrist and hands compared to the responsiveness of synovitis in a 6 month period follow-up, to compare the responsiveness of finger flexor tenosynovitis with the responsiveness of wrist extensor tenosynovitis and to describe the subclinical synovitis and tenosynovitis in RA patients in clinical remission. MATERIAL AND METHODS Fifty seven patients with active RA starting biologic therapy were included. Clinical, laboratory, and US evaluations were performed at baseline, 1, and 6 months. US evaluation included wrist and MCPs 2-5 joints, bilaterally for synovitis and extensor tendons compartments 2, 4, and 6 and finger flexors 2-5 for tenosynovitis. Eighteen US scores based on semiquantitative or binary grades were calculated at each visit. Responsiveness of synovitis and tenosynovitis scores was calculated using the standardized response mean (SRM). RESULTS The responsiveness of US tenosynovitis was lower comparing with the responsiveness of US synovitis but both showed large effect of therapy. Furthermore, tenosynovitis responsiveness was similar to CRP responsiveness (SRM -0.90). Finger flexors tenosynovitis showed a higher responsiveness than extensor tenosynovitis on GS (-0.94 compared to -0.63) and a lower SRM on PD (-0.56 compared to -0.85). Tenosynovitis scores remission was overlapping clinical remission according to CDAI and SDAI in 100% of cases. Overall there was less subclinical tenosynovitis than subclinical synovitis at final visit according to clinical activity indices. CONCLUSION Tenosynovitis US scoring in RA may be as good as synovitis scoring for characterization of disease activity and responsiveness.

OP0157 Clinical Response of Disease Activity, Disability and Mobility Indices in Relation to Anti-Drug Antibody in the Planetas

Background Recently, the European Medicines Agency approved a biosimilar to infliximab, CT-P13. Biosimilars are not only required to have biochemical and pharmacokinetics (PK) equivalence, but also must demonstrate similarity in their therapeutic effectiveness, safety and immunogenicity. The PLANETAS was a randomized double-blind, parallel group study for demonstrating PK equivalence between biosimilar infliximab (CT-P13) and innovator infliximab (INX) in patients with ankylosing spondylitis (AS). Objectives To compare disease activity, disability and mobility indices of CT-P13 and INX and to assess the effect of anti-drug antibody (ADA) on the observed indices in patients participated in the PLANETAS. Methods In the PLANETAS, key secondary endpoints captured the clinical measures of disease activity via ASAS20/40 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), disability via the Bath Ankylosing Spondylitis Functional Index (BASFI) and mobility via the Bath Ankylosing Spondylitis Metrology Index (BASMI). The Students t test was used to compare mean change of three indices from baseline in both treatment groups. ADA was measured using the electrochemiluminescent methodology. Clinical responses, regardless of treatment groups, were examined in relation to the presence of the ADA. Results 250 patients with AS were treated with either CT-P13 or INX. Baseline comparability was demonstrated with each of these 3 indices. At week 54, BASDAI improved significantly from baseline in both treatment groups (CT-P13: from 6.74 to 3.78 and INX: from 6.57 to 3.70) and this improvement was similar between groups (difference of means -0.29; CI of the difference -0.91 to 0.32). BASFI and BASMI also improved in similar pattern: BASFI (CT-P13: from 6.20 to 3.42 and INX: from 6.24 to 3.46) and BASMI (CT-P13: from 4.0 to 2.8 and INX: from 4.1 to 3.2). At week 54, 50% improvement of the baseline BASDAI (BASDAI50) was achieved in 44.3% for CT-P13 and 46.3% for INX and BASDAI50 response rate was comparable between the two groups (p=0.7737). Overall, no statistical significance in clinical responses between the treatment groups at week 54 was found for all indices. Higher ASAS20/40 responses were seen in the ADA negative patients (72.7%/56.5%) compared with ADA positive patients (54.7%/37.7%) at week 54. Mean change from baseline for BASDAI and BASFI improved significantly in ADA negative subgroup than ADA positive subgroup (BASDAI: -3.13 vs. -2.30 and BASFI: -2.97 vs. -2.18) but no clear association with ADA was seen for BASMI. Conclusions Well-established indices of disease activity, disability and mobility in patients with AS were improved and statistically similar between CT-P13 and INX group. ASAS20/40, BASDAI and BASFI by ADA subgroup showed evidence of a relationship which was higher clinical responses in ADA negative subgroup. Disclosure of Interest W. Park Grant/research support: Celltrion, Consultant for: Celltrion, Speakers bureau: Celltrion, D. H. Yoo Grant/research support: Celltrion, Consultant for: Celltrion, Speakers bureau: Celltrion, S. Szántό: None declared, F. Berghea: None declared, M. Brzosko Grant/research support: Celltrion, P. Wiland Grant/research support: Celltrion, S. Smiyan Grant/research support: Celltrion, R. Araiza-Casillas Grant/research support: Celltrion, F. Díaz-González Grant/research support: Celltrion, J. H. Suh Employee of: Celltrion DOI 10.1136/annrheumdis-2014-eular.3804

Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study

BACKGROUND Guselkumab, a human monoclonal antibody that binds to the p19 subunit of interleukin 23, has been approved for the treatment of moderate-to-severe psoriasis. Psoriatic arthritis is a common comorbidity of psoriasis with an umet need for novel treatments. We assessed the efficacy and safety of guselkumab in patients with active psoriatic arthritis. METHODS We did a randomised, double-blind, placebo-controlled, phase 2a trial at 34 rheumatology and dermatology practices in Canada, Germany, Poland, Romania, Russia, Spain, and the USA. Eligible participants were aged 18 years or older with active psoriatic arthritis and plaque psoriasis affecting at least 3% of their body surface area, with three or more of 66 tender joints and three or more of 68 swollen joints, who had an inadequate response or intolerance to standard treatments. We randomly assigned patients (2:1) via a central interactive web-response system using computer-generated permuted blocks with a block size of six, stratified by previous anti-tumour necrosis factor-α use, to receive subcutaneous guselkumab 100 mg or placebo at week 0, week 4, and every 8 weeks thereafter for 24 weeks. Patients, investigators, and site staff were masked to treatment assignment until final database lock at week 56. At week 16, patients with less than 5% improvement in swollen and tender joint counts were eligible for early escape to ustekinumab. At week 24, the remaining placebo-treated patients crossed over to receive guselkumab 100 mg at weeks 24, 28, 36, and 44 and guselkumab-treated patients received a placebo injection at week 24, followed by guselkumab injections at weeks 28, 36, and 44. The primary endpoint was the proportion of patients with at least 20% improvement at week 24 in signs and symptoms of psoriatic arthritis according to American College of Rheumatology criteria (ACR20) in the modified intention-to-treat population (ie, all randomly assigned patients who received at least one dose of study treatment). Safety analyses included patients according to the study drug received. This study is registered with ClinicalTrials.gov, number NCT02319759. FINDINGS Between March 27, 2015, and Jan 17, 2017, we randomly assigned 149 patients to treatment: 100 to guselkumab and 49 to placebo. 17 (35%) of 49 patients in the placebo group and ten (10%) of 100 patients in the guselkumab group were eligible for early escape to ustekinumab at week 16. 29 (59%) of 49 patients in the placebo group crossed over and received guselkumab at week 24. Three (6%) of 49 patients in the placebo group, one (3%) of 29 patients who crossed over from placebo to guselkumab, and six (6%) of 100 patients in the guselkumab group discontinued study treatment before week 44. 58 (58%) of 100 patients in the guselkumab group and nine (18%) of 49 patients in the placebo group achieved an ACR20 response at week 24 (percentage difference 39·7% [95% CI 25·3-54·1]; p<0·0001). Between week 0 and week 24, 36 (36%) of 100 guselkumab-treated patients and 16 (33%) of 49 placebo-treated patients had at least one adverse event. The most frequent adverse event was infection in both groups (16 [16%] of 100 patients in the guselkumab group vs ten [20%] of 49 patients in the placebo group). The prevalence of adverse events between week 0 and week 56 in guselkumab-treated patients (51 [40%] of 129) indicated no disproportional increase with longer guselkumab exposure. No deaths occurred. INTERPRETATION Guselkumab, a novel anti-interleukin 23p19 antibody, significantly improved signs and symptoms of active psoriatic arthritis and was well tolerated during 44 weeks of treatment. The results of this study support further development of guselkumab as a novel and comprehensive treatment in psoriatic arthritis. FUNDING Janssen Research & Development.

Concepts in diagnosing, scoring, and monitoring tenosynovitis and other tendon abnormalities in patients with rheumatoid arthritis- the role of musculoskeletal ultrasound.

In the last years, important advancements have been made in implementing high resolution imaging related information inside the global management algorithm in RA patients. Musculoskeletal ultrasound has already proven its utility in visualizing directly the joint synovial tissue, the synovial vascularization and in monitoring the response to therapy. Recently, much attention has been given to the presence of tenosynovitis, as a constant, complementary but different facet of the inflammatory involvement in RA. Tenosynovitis identification in early RA stages may allow adequate treatment adjustment in early and established disease in order to prevent and/ or slow down the development of structural damage at tendon and joint level.

AB1158 Prevalence of comorbidities in psoriatic arthritis: a cross-sectional study

Background Psoriatic arthritis (PsA) is associated with important comorbidities: cardiovascular, gastro-intestinal, infectious, malignant, and psychiatric [1, 2]. However, they are less studied in PsA compared to other chronic inflammatory arthritis. Objectives The objective of this study was to calculate the prevalence of comorbidities and risk factors in a cohort of PsA patients. Methods This was an observational cross-sectional study, including consecutive, unselected adult patients, with a diagnosis of PsA according to their rheumatologist. Data collected: demographical, clinical (affected joints, current psoriasis, axial involvement, enthesitis, dactylitis), biological (acute phase reactants), and treatment related (nonsteroidal anti-inflammatory drugs, synthetic remissive drugs and biologics). Data on comorbidities and risk factors were collected according to the European League Against Rheumatism (EULAR) recommendations on reporting comorbidities in chronic inflammatory rheumatic diseases in daily practice [3]. Results In all, 129 PsA patients were included: 77 (59.7%) women, mean age ± standard deviation 53.5±11.8 years, disease duration 7±7.4 years; 53 (41.1%) had axial involvement, 33 (25.6%) dactylitis, 18 (14%) enthesitis, and 24 (18.6%) current moderate/severe psoriasis. Most of them had low or moderate disease activity and almost a quarter of them (32; 24.8%) were taking a biologic. The most prevalent comorbidities were: dyslipidaemia 103 patients (79.8%), hypertension 67 (51.9%), obesity 44 (34.1%), diabetes 21 (16.3%) and ischemic heart disease 15 (11.6%). Almost a third of patients (42, 32.6%) suffered a cardiovascular event after their PsA diagnosis, of which heart attack 2 patients, stroke 4, cardiac failure 4 and peripheral arterial disease one patient. Cardiovascular events correlated with smoking (r=0.893, p<0.001) and current moderate/severe psoriasis (r=0.218, p=0.013). Regarding infectious comorbidities: 11 patients (8.5%) had a history of tuberculosis after being diagnosed with PsA, 7 (5.4%) chronic viral hepatitis, of which 4 with B virus and 3 with C virus, and 5 patients (3.9%) developed severe infections. Five patients (3.9%) were diagnosed with neoplasia, but no correlation was identified with any of the clinical, biological or treatment related included variables. Only 11 patients (8.5%) were diagnosed with depression, but the prevalence is probably underestimated, since not all patients were screened to this end. Conclusions PsA is associated with a high prevalence of comorbidities, especially cardiovascular diseases. This should be taken into consideration in the therapeutic and the global management of PsA patients. References Husni ME, Mease PJ. Managing comorbid disease in patients with psoriatic arthritis. Curr Rheumatol Rep 2010;12(4):281–7. Ogdie A, Yu Y, Haynes K, et al. Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: apopulation-based cohort study. Ann Rheum Dis 2015;74(2):326–32. Baillet A, Gossec L, Carmona L, et al. Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative. Ann Rheum Dis 2016;75(6):965–73. Disclosure of Interest None declared

FRI0256 Significance of Cognitive Impairment in Systemic Sclerosis

Background There is an increased appreciation of the burden of cognitive impairment in people with autoimmune diseases (1). Recent studies have demonstrated that patients with systemic sclerosis (SSc) have a specific pattern of cognitive impairment: the dysexecutive syndrome (2). Objectives We evaluated the prevalence of cognitive impairment in SSc and assessed the association with the disease features and impact on daily living Methods Consecutive SSc from EUSTAR center 096 were examined. Montreal Cognitive Assessment (MoCA) was used to assess cognitive dysfunction and scores ≤26 were considered abnormal (3). SSc patients were assessed according tu MEDS evaluation sheets to determine organ involvement, autoantibody profile, disease activity (Valentine Activity Index) and disease severity (Medsger Severity Index). sHAQ (Scleroderma Health Assessment Questionnaire) has also been completed. Data were compared by difference tests according to the types of variables: t-test, Mann-Whitney or chi-square. To evaluate correlations between variables Pearson or Spearman correlations were used. Results A total of 70 SSc patients [36 (51.42%) limited SSc (lSSc) and 34 (48.57%) with diffuse SSc (dSSc), 60 female; mean age 54.5 (±11.62) years; mean disease duration 66 (±429.6) months] were included in the study. 47.14% of the patients had active disease, the mean Rodnan score was 7 (±4.17), the mean Medsger score was 5.5 (±2.89), 24.28% of the patients had lung involvement and 20% had pulmonary arterial hypertension. The mean HAQ was 1 (±0.59). Cognitive impairment was identified in 65.71% SSc patients; the mean MOCA score was 26 (±2.83). Cognitive impairment of SSc patients was related to older age (r=-0.378, p=0.001), rural provenience (r=-0.351,p=0.003), severity of the disease evaluated by the Medsger score (r=–0.262,p=0.029) and poor quality of life evaluated by sHAQ (r=-0.323,p=0.003).Correlations were also identified with musculoarticular involvement (r=-0.330,p=0.006), advanced capillaroscopy patttern (r=-0.331, p=0.006). The diiffuse SSc patients were more likely to have cognitive dysfunction (likehood ratio 0.012) as were those with SCL70 positive (0.0.18). No relationship was identified between cognitive impairment and lung, heart or renal involvement, the presence of digital ulcers, the use of corticosteoids or immunosuppression. Conclusions An increased prevalence of cognitive impairment was observed in SSc and associated with age, rural provenience, more severe disease, muscle involvement and poor quality of life. Further studies are needed to be compared with healthy controls and to assess the role of microvascular damage or that of other confounders. References T.N.Amaral et al. Prevalence and significance of cognitive impairment in systemic sclerosis Ann Rheum Dis 2015;74:605 Ylmaz N. et al Dysexecutive syndrome: a specific pattern of cognitive impairment in systemic sclerosis Cogn Behav Neurol. 2012 Jun;25(2):57–62. www.mocatest.org/normative-data/ Disclosure of Interest None declared

AB0934 Blood Pressure Is Not Changed by Topical Nsaid – A Pilot Continuous Automated Blood Pressure Monitor Study

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used by rheumatic patients for both acute and chronic conditions. A certain increase in blood pressure of 3–5 mmHg seems to be a NSAID class effect. Although the effect appears from the beginning of the treatment, due to his“modest” amplitude, it was largely ignored both by patients and physicians. However, new epidemiological data suggest that such a small increase in BP could produces in USA about 21.000 deaths per year (higher than in case of gastrointestinal deaths produced by the unprotected usage of nonselective NSAID). For the time being we do know that topical and systemic NSAID have similar therapeutic effect on superficial exposed joints (e.g. knee, wrists, elbows etc). Objectives The aim of the study was to evaluate whether or not the use of topical NSAIDs in rheumatic patients affects blood pressure or pulse rate values. Methods This was a prospective study which included patients diagnosed with various rheumatic diseases using a continuous Automated BP Monitoring (ABPM): both BP and pulse rate have been continuously recorded for 48 hours at baseline (24 hours without topical NSAID use) and day1 (24 hours with topical NSAID use). Same NSAID (namely Aceclofenac) in same dose was used in all cases. Subjects that changed their concomitant medication have been excluded from the analyses. Daytime (0700–2200), nighttime (2201–0659) and all-day (24h) systolic and diastolic BP along with pulse rate values have been analyzed. Difference between Baseline and Day1 have been tested by using ANOVA and Fisher exact test; a p<0.05 was considered significant. Results 15 subjects have been evaluated between October 2015 to January 2016. The meanSystolic BP varied between 101.75 and 147.9 in Baseline respectively between 103.9 and 132.25 during D1. The mean diastolic BP varied between 55.5 – 88.1 in Baseline and respectively between 56.4–82.5 during D1. Pulse varied between 60.2 and 95.9 in Baseline and respectively 59.3 and 90.2 during Day1. No difference between baseline and Day1 have been identified for Systolic or DiastolicBP, cardiac pulse; same results have been obtained for all-day, nighttime and daytime subanalysis. Conclusions Although this study has certain limitations our data suggest no significant change in BP or cardiac pulse associated to topic use of NSAID (in our case Aceclofenac). Larger studies should be made to confirm the conclusion of this pilot study. References Snowden S, Nelson R- The effects of nonsteroidal anti-inflammatory drugs on blood pressure in hypertensive patients. Cardio Rev2011 Jul-Aug;19(4):184–91. Howard Lee,MD; KeeSikKim,MD,- Ambulatory Blood Pressure Response to Once-Daily Fimasartan: An 8-Week, Multicenter, Randomized, Double- Blind, Active-Comparator, Parallel-Group Study in Korean Patients With Mild To Moderate Essential Hypertension Clinical Therapeutics/Volume 35, Number 9, 2013. Disclosure of Interest None declared

A5.4 Prevalence of comorbidities in Paget’s disease of the bone a single centre report

Background and objectives Paget disease (PD), also known as osteitis deformans, is characterised by single or multiple bone site alteration, including accelerated osteoclast-mediated resorption followed by increased low quality bone production. This process results in a disorganised, unsteady structure that may lead to bone deformity. This condition affects elderly adult population, with a slightly higher predominance in males and it is thought to have important genetic determinants. The association of comorbid conditions places a burden on the patients and imposes regular monitoring. The present study aims to evaluate associated medical conditions in patients suffering from PD. Methods We retrospectively identified 39 patients who were diagnosed with PD, based on clinical presentation, plain x-rays, scintigraphy or when necessary biopsy or bone turnover markers’ detection. For the study group we noted the presence of cardiovascular disorders – hypertension, ischaemic heart disease or rhythm abnormalities such as atrial fibrillation. Median body mass index (BMI) was calculated. Neurologic conditions namely hearing loss, Parkinson’s disease or cerebral stroke history were taken into account, as well as type 2 diabetes and prostate adenoma. Tobacco use was also assessed for the study group. Development of neoplasia was reviewed. Information was gathered from patients’ clinical charts over a period of one year. Results Out of the 39 patients included in the study lot, 64.1% were males and 35.9% of female gender (1.7:1 ratio) with a mean age of 65.67 years, who were mainly diagnosed on the basis of clinical and radiographic assessment (97.4%). 7.6% had positive family history of PD. The polyostotic form of PD encountered in 26 patients (66%) is prevalent over the monostotic pattern (13, 33.3%). The most common affected sites were the hip in 71.0% of patients, skull (44.7%), femoral bone (26.3%) and the lumbar spine (21.05%). 61.5% of patients were hypertensive while 28.2% associated ischaemic heart disease. 27.6% were priorly diagnosed with atrial fibrillation. Mean BMI value was calculated at 27.7 kg/m². 12.8% of patients were hypoacusic, 5.1% suffered from a cerebral stroke and the same percentage were diagnosed with Parkinson’s disease. 52% of males had prostate adenoma, 15.3% suffered from type 2 diabetes. 20.5% patients confirmed smoking status. Three patients developed neoplasia, namely squamous cell carcinoma, carcinoma of the breast and rectum with no correlation to disease duration. Conclusions Taking into consideration the difficulties that PD brings with it, associated comorbidities tend to diminish further the health and quality of life in these patients. Therefore a complete medical check-up is recommended on each follow up visit in order to improve their status.

A5.6 Muscular weakness and pain in patients with rheumatoid arthritis - correlations with electromyography, clinical and serological data

Background and objectives Muscular involvement (mostly by weakness, pain and fatigue) is frequently involved in rheumatological practice. Associated myopathy to rheumatoid arthritis (RA) is an important comorbity that causes supplementary disability. Our objectives are to investigate the muscular involvement in RA with electromyography (amplitude, duration and motor unit potential MUP) and to correlate the data with clinical and laboratory findings. Material and methods Consecutive patients with RA, weakness and muscle pain were recruited during a 9 month period. Clinical (VAS, muscular testing, 6 min walk test) and laboratory tests (creatinkinase, dehydrogenase lactate, inflammatory markers, vitamin D serological level) were performed. The electromyographic study was pursued with concentric needle for MUP evaluation, then amplitude, duration and polyphasic pattern at deltoid muscle, interosseous, vastus lateralis and anterior tibial muscle were registered. Results 50 patients (88% women, mean age 62.8 +/-11.5 years) diagnosed with PR and muscle weakness were included. Clinically, DAS 28 (mean 3.76+/-1.44), HAQ (mean 1.49+/-1.12), VAS scale pain (mean 5.18+/-2.5), time up and go test (mean 12.62+/-5.78 min) and 6 min walk test (mean 277.306+/-153.34 metres) were reported. DAS 28 correlates positively with serological levels of creatinkinase (0.768, p < 0.00), C reactive protein (0.421, p < 0.00) and vitamin D level (0.871, p < 0.00) also with polyphasic pattern at deltoid level and duration of MUP in vastus lateralis muscle (0.768, p < 0.00). Polyphasic pattern in the upper limb is related to a similar pattern in lower limb muscles (0.510, p < 0.00). Lower duration of action potential was found in: deltoid (64% of cases), anterior tibial (58%), interosseous (44%) and vastus lateralis muscle (36%). Conclusion Associated myopathy to RA affects quality of life and function impairment in upper and lower limbs. DAS 28 correlates also with myopathic involvement and vitamin D levels in patients with RA. Most affected muscles are deltoid and anterior tibial muscle. Both upper and lower limbs muscles showed similar polyphasic pattern on electromyography.