T. Gudu

Monitoring Drug and Antidrug Levels: A Rational Approach in Rheumatoid Arthritis Patients Treated with Biologic Agents Who Experience Inadequate Response While Being on a Stable Biologic Treatment

Clinical response in patients with rheumatoid arthritis (RA) treated with biologic agents can be influenced by their pharmacokinetics and immunogenicity. The present study evaluated the concordance between serum drug and antidrug levels as well as the clinical response in RA patients treated with biological agents who experience their first disease exacerbation while being on a stable biologic treatment. 154 RA patients treated with rituximab (RTX), infliximab (IFX), adalimumab (ADL), or etanercept (ETN) were included. DAS28, SDAI, and EULAR response were assessed at baseline and reevaluated at precise time intervals. At the time of their first sign of inadequate response, patients were tested for both serum drug level and antidrug antibodies level. At the next reevaluation, patients retreated with RTX that had detectable drug level had a better EULAR response (P = 0.038) with lower DAS28 and SDAI scores (P = 0.01 and P = 0.03). The same tendency was observed in patients treated with IFX and ETN regarding EULAR response (P = 0.002 and P = 0.023), DAS28 score (P = 0.002 and P = 0.003), and SDAI score (P = 0.001 and P = 0.026). Detectable biologic drug levels correlated with a better clinical response in patients experiencing their first RA inadequate response while being on a stable biologic treatment with RTX, IFX, and ETN.

Fatigue in psoriatic arthritis - a cross-sectional study of 246 patients from 13 countries.

OBJECTIVESnFatigue is an aspect of psoriatic arthritis (PsA), which is important to patients. The objective was to evaluate magnitude of fatigue in PsA patients and to assess factors that might explain high levels of fatigue.nnnMETHODSnThis was an ancillary analysis of a cross-sectional study in 13xa0countries of unselected PsA patients who fulfilled the CASPAR criteria. Patient-perceived importance of fatigue was assessed through a priority exercise. Levels of fatigue were assessed by a numeric rating scale (range 0-10). Factors potentially associated with fatigue>5/10: i.e., demographic variables (age, gender, disease duration, education level) and disease related characteristics including joint counts, C-reactive protein, skin psoriasis, axial involvement, enthesitis, dactylitis, structural damage, were assessed by univariate, multivariate logistic and multiple linear regression.nnnRESULTSnIn all, 246xa0patients were analysed: mean±standard deviation age 51.2±13.0years, mean disease duration 9.9±10.1years, mean DAS28 3.5±1.3. Fatigue was ranked second in patient-perceived importance, after pain. Magnitude of fatigue was high: mean fatigue 5.0±3.0. Fatigue>5/10 was well explained (variance explained 73%) by skin psoriasis (odds ratio 4.67 [95% confidence interval 1.05; 20.72]), tender joints (1.30 [1.01; 1.68]) and lower education level (1.09 [1.02; 1.23]). In the multiple linear regression model, fatigue was explained by skin psoriasis, tender joints, enthesitis, female gender, education level.nnnCONCLUSIONSnFatigue is a priority for PsA patients. Fatigue levels were high in these patients and fatigue>5/10 was mainly associated with disease-related factors but also patient-related variables, indicating that the etiology of fatigue in PsA is multifactorial.

Statins Do Not Influence Long-Term Rituximab Clinical Efficiency in Rheumatoid Arthritis Patients

Objective. This longitudinal study aims to determine if statins inhibit the response to rituximab in rheumatoid arthritis (RA) patients. Methods. 41 patients initiating rituximab were included; 17 patients were exposed to the combination of statins and rituximab. The total cholesterol, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed. The clinical response was evaluated using Disease Activity Score (DAS28) and European League against Rheumatism (EULAR) response at 6 and 18 months. Results. A tendency of increasing in DAS28 was observed in statin-exposed group but the correlation was very weak (at 18 months: r = 0.013, P = 0.952). The statin-exposed status was negatively and very weakly correlated with EULAR response at 6 months (r = −0.073, P = 0.661) and 18 months (r = −0.197, P = 0.244). There was a negative correlation between statin-exposed status and inflammatory markers values (ESR and CRP); however, the correlation was very weak. The use of statin did not influence the cardiovascular risk measured by modified Systematic Coronary Risk Evaluation (mSCORE). Conclusions. Long-term significant inhibitory effects of statins on rituximab treatment in RA have not been proved using clinical response scores or biologic markers.

Mapping the Effect of Psoriatic Arthritis Using the International Classification of Functioning, Disability and Health

Objective. The effect of a disease can be categorized by a standardized reference system: the International Classification of Functioning, Disability and Health (ICF). The objective was to map the effect of psoriatic arthritis (PsA) from the patient’s perspective to the ICF. Methods. A systematic literature review was performed. Qualitative publications reporting domains of impact important for patients with PsA were identified using the following terms: (“psoriatic arthritis”) AND (“quality of life” OR “impact”). Meaningful concepts were extracted from the publications, grouped into domains and linked to the ICF categories. The number of concepts linked to each ICF category and to each ICF level was calculated. The number of concepts not linkable was also calculated. Results. Eleven studies (13 articles) were included in the analysis. Twenty-five domains of impact were cited, of which the ability to work/volunteer and social participation were the most cited (both by 10 studies). In total, 258 concepts were identified, of which 217 could be linked to 136 different ICF categories; 41 concepts, mostly personal factors, could not be precisely linked. The most represented ICF component was activities and participation (42.6%) rather than body structures (10.3%) or body functions (29.4%). Ten studies (90.9%) reported impairments in the ability to work/volunteer and social participation, and 7 (63.6%) reported leisure activities, family and intimacy, pain, skin problems, and body image. Conclusion. PsA widely affects all aspects of patients’ lives, in particular aspects related to activities and participation. The ICF is a useful approach for the classification of disease effect.

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

AB0647 Diagnosis of systemic sclerosis – “a tangled story”

Background Proper diagnosis of scleroderma is often long and difficult, since it is such a rare disease, and one which few doctors or patients are familiar with. Objectives To establish the interval between the symptoms onset of systemic sclerosis (SSc) and what type of investigations are performed until the patients reach the final diagnosis of a rheumatologist Methods This is a cross-sectional study that included randomly selected patients with a a diagnosis of SSc which were evaluated based on a questionnaire about symptoms at onset, specific consults and investigations. Descriptive statistics were used. Results The study group included 47 patients, of which only 5 were males and 17 from rural areas.The medium age was 53 (14.4) years. First symptom of onset was Raynaud phenomena 91.3% of the cases, followed by skin changes (56.5%), puffy fingers (52,2%), gastrointestinal and musculoarticular symptoms (23.9% each). The medium duration between the first symptom and a medical consult was 6 (63.5) months. The first medical consult was done by a internal medicine specialist -38.3%, by a rheumatologist-29.8%, a gastroenterologist-12.8%, a dermatologist-8.5%, a nephrologist and a pneumologist-4.2% and neurologist 2.1% The first suspected diagnosis was SSc in 14 cases, Raynaud syndrome in 8, connective tissue disease in 5, rheumatoid arthritis in 4, cancer, autoimmune hepatitis, idiopathic pulmonary fibrosis each in 2 cases and none in 10 cases. The medium number of consults until final diagnosis was 3.4 (1.7). The medium duration from the first symptom until the correct diagnosis was 39.2 (74) months. The first investigations recommended were blood tests in almost all of the patients (95.7%), but only a third of them included specific scleroderma autoantibodies. Capillaroscopy was performed as an initial diagnostic test in only 6 patients (12.8%). The mean interval from disease onset until the patient was referred to the first capillaroscopy was 13.5 (28.8) months, to specific autoantibodies was 40.17 (61.3) month, to echocardiography was 36.38 (54) months, to lung function tests and lung CT – 41.76 (65.8) months. There were no significant statistical differences between patients coming from rural environment and those coming from urban environment. The only significant statistical difference between diffuse and limited subset was the time the patient was referred to echocardiography (19.8 (47.6) months for the diffuse subset, 66.8 (94.6) months for the limited subset, p=0.04). The only statistical difference between males and females was related to the interval that capillaroscopy was performed (14 (20.5)months in females, 4.8 (5) months in males, p=0.02). Conclusions Scleroderma is a less well-known disease. This lack of awareness contributes to delayed diagnosis and delayed onset of therapy. Often such diagnostic uncertainty and frustration takes a huge toll on the psychological well-being of these patients, who describe their journey to diagnosis as being one of the most difficult part of their illness. One of our missions as rheumatologist is to increase recognition of this disorder. References https://www.sclero.org/scleroderma/diagnosis/difficult. Disclosure of Interest None declared

Knee ultrasound from research to real practice: a systematic literature review of adult knee ultrasound assessment feasibility studies.

OBJECTIVEnTo identify and analyse existing data regarding knee ultrasound (US) feasibility in clinical practice. Materialxa0and methods: A systematic literature review was performed using the terms: (knee) AND (ultrasound OR ultrasonography)xa0AND (feasibility OR pilot OR proof of concept). Feasibility studies regarding knee US or US aided maneuver involving knee joint, published during 2005-2015, were selected and evaluated against a complex framework constructed around mandatory key areas for feasibility studies: acceptability, demand, implementation, practicality, adaptation, integration andxa0expansion.nnnRESULTSnOne hundred and fifty-nine publications were identified, of which 9 were included in the final analysis: 6xa0dealt with the development and implementation of novel US scores, while the rest focused on implementing MSUS in clinicalxa0practice, evaluating the usefulness of articular cartilage US assessment and the feasibility of sonography for intra-articularxa0knee injections, respectively. Six studies quantified feasibility as time spent for the evaluation, with only two addressing areassuch as acceptability, implementation and practicality, although none of these systematically assessed all feasibility domains.nnnCONCLUSIONnKnee US feasibility is still poorly addressed; the time required for US assessment is the main area addressed.xa0This information gap should be properly addressed in future works, in order to ensure the right place for this technique.

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

THU0637 Impact of Psoriatic Arthritis: Linking The Domains of Health Which Are Important for Patients with Psoriatic Arthritis To The International Classification of Functioning, Disability and Health

Background The impact of psoriatic arthritis (PsA) is wide-reaching and covers various aspects of life, e.g., physical, psychological and social. This impact could be categorised using a universally accepted, standardized reference system: the International Classification of Functioning, Disability and Health (ICF). Objectives The objective was to assess how the impact of PsA from the patients perspective mapped to the ICF. Methods Data sources: Publications with dimensions of health important for PsA patients were identified through a systematic literature review using the following terms: (“psoriatic arthritis”) AND (“quality of life” OR “impact”). Only studies related to impact from the patients perspective, i.e., studies using qualitative methodology (e.g., focus groups, individual interviews) or instruments that were patient derived (patients included in the development task force, development based on qualitative methods) were included. Data extraction and interpretation: Domains of health important for patients were identified. Meaningful concepts were extracted from the publications and linked to the ICF categories, according to the updated linking rules [1] by 2 persons. The number of concepts linked to each ICF category and to each ICF level was calculated. The number of concepts not linkable was also calculated. Descriptive statistics were used. Results Eleven studies (13 articles) were included in the analysis, corresponding to 2893 patients (of whom 623 assessed qualitatively); two studies did not precisely define the population involved in their qualitative phases. Eight studies were exclusively on PsA and the other 5 included also patients with only psoriasis; only 5 studies were qualitative per se. Twenty-five domains of health were cited, of which Ability to work/volunteer and Social participation were most cited (both by 10 studies). In total 258 concepts were identified, of which 217 (84.1%) could be linked to 136 different ICF categories; 41 concepts (15.9%), mostly personal factors, namely coping with the disease (21 concepts; 51.21%) could not be linked. The most represented ICF component was Activities and Participation (42.6%) rather than Body functions (29.4%) or Body structures (10.3%). Ten studies (90.9%) reported impairments in Ability to work/volunteer and Social participation; 7 (63.6%) reported Leisure activities, Family and intimacy, Pain, Skin problems and Body image. Conclusions PsA widely impacts all aspects of patients lives, in particular regarding activities and participation, reflecting the functional limitations, but also the psycho-social and societal burden of PsA. The ICF is a useful approach for the systematic classification of disease impact. References Cieza A, Geyh S, Chatterji S et al. ICF linking rules: an update based on lessons learned. J Rehabil Med 2005;37:212–8. Acknowledgement Dr. Gudus work was supported by a scientific training bursary of the European League Against Rheumatism. Disclosure of Interest None declared

AB0457 How Much Different Is Juvenile Onset Systemic Lupus Erhytematosus? Data from A Romanian Cohort

Background Systemic Lupus Erhytematosus (SLE) is a multiorgan disease in which pattern of evolution is linked to activity and damage. When the disease starts at an early age, all the outcomes might be influenced by this. Objectives The main focus of this study is to describe the differences between juvenile and adult onset SLE in a Romanian cohort. Methods 101 SLE patients were evaluated between March 2015 and December 2015. Patients were diagnosed with SLE according to ACR classification criteria and splited in 2 groups, taking into account age at disease onset: before and after 18. All patients agree to participate in this study. Data about demographic, clinical or serological characteristics, activity (SLEDAI) or damage (SLICC damage index SDI), treatment were collected. Statistical analisys was performed with SPSS 20.0. Results Our cohort was made from 18 patients with juvenile onset SLE and 83 with adult onset SLE. Mean age at diagnosis was 14.05 versus 37.89. The juvenile onset SLE group had significant more autoimmune disease as family background, mainly SLE and rheumatoid arthritis (33.3% versus 12.04%, p 0.025), significant more severe organ involvement during the disease evolution: SLE related neurologic involvement 33.3% versus 12% (p 0.025) and renal involvement 50% versus 16.8% (p 0.023), more frequent anti dsDNA Ab positives 88.8% versus 60.24% (p 0.021). This more severe pattern of evolution is also reflected by immunosuppressant therapy, Cyclophosphamide being used in juvenile subgroup in 66% cases versus 35.3% in adults (p 0.014). Interesting, there were no differences between cumulative damage between groups, as measured by SDI (p 0.24), with the mention that in juvenile onset patients, SDI>1 was more frequent SLE related. This is in line with the fact that side effects of the corthicotherapie were identified more in adult onset SLE 61.44% versus 33.3% in juvenile onset (p 0.029). Conclusions Our data clearly show that juvenile onset SLE has more genetic background and it is more prone to a severe disease, renal and neurologic involvement being more frequent than in adult onset form. Severity seems to be related both to the activity, but also to fast damage accrual over time. Controlling the disease activity must be our goal, since cumulative irreversible damage is mainly SLE related for our patients. References Watson, L., Leone, V., Pilkington, C., et all, on behalf of the UK Juvenile-Onset Systemic Lupus Erythematosus Study Group, “Disease activity, severity, and damage in the UK juvenile-onset systemic lupus erythematosus cohort”. Arthritis & Rheumatism, 2012, 64: 2356–2365. doi: 10.1002/art.34410. Disclosure of Interest None declared