M. van der Ven

THU0108 No Clear Association Between the Presence of Subclinical Synovitis and Patient Reported Outcomes in RA Patients in Remission

Background Several studies assessed disease activity with ultrasound in rheumatoid arthritis (RA) patients who were in clinical remission. These studies found subclinical synovitis in 48-73% of the patients. Subclinical synovitis is associated with radiographic progression and predicts short-term relapse in RA patients. So far, little is known about the association between subclinical synovitis and patient reported outcomes (PROs). Objectives We evaluated the frequency of subclinical synovitis detected by ultrasound in RA patients in clinical remission while they are continuing synthetic and biological DMARDs. Our second objective was to compare PROs between patients with and without subclinical synovitis. Methods Patients who are treated with the combination of a synthetic DMARD and biological DMARD (adalimumab or etanercept) and have low disease activity (DAS44<2.4 and SJC ≤1) were examined by ultrasound at baseline and after three months follow-up. Ultrasound examination included 26 joints (MCP2-5, PIP2-5, wrists, MTP2-5) graded on greyscale (GS; 0-3) and power Doppler (PD; 0-3). A joint with subclinical synovitis was defined as GS>1 and/or PD>0. Data on clinical and psychological characteristics, demographics, pain scores, functional ability (HAQ) and health-related quality of life (SF-36) were collected at baseline and at three months. Coping (Pain Coping and Cognition List [PCCL]), depression/anxiety symptoms (Hospital Anxiety and Depression Scale [HADS]) and fatigue (Bristol RA Fatigue Multi-Dimensional Questionnaire [BRAF-MDQ] and Fatigue Assessment Scale [FAS]) were collected at three months follow-up. Ultrasound subclinical synovitis positive and negative patients were compared on their PROs using the Wilcoxon-Mann-Whitney test and Chi-square test. Results At baseline, 89 patients were included of which 71 patients had had their three months evaluation. Ultrasound revealed subclinical synovitis in 64% of the patients at baseline and in 68% at three months. In 44% of the patients subclinical synovitis was detected at both measurements. figure 1 shows baseline characteristics and patient reported outcomes at baseline and after three months. No clear pattern emerged on the PROs scores between subclinical synovitis positive and negative patients. At baseline functional ability differed between the two groups while health-related quality of life was similar. At three months similar levels were observed for functional ability, health-related quality of life, coping, depression symptoms and fatigue. HADS anxiety differed at 3 months. Conclusions Subclinical synovitis is common in RA patients in clinical remission while they continue synthetic and biological DMARDs. In our study population we could not find a clear association between subclinical synovitis and PROs. Disclosure of Interest None declared

FRI0562 Ultrasound Enthesitis in Primary Care Psoriasis Patients with Musculoskeletal Complaints

Background Psoriasis patients with enthesitis can classify as psoriatic arthritis since the introduction of the CASPAR classification criteria in 2006. However, clinical assessment of the entheses could be challenging. In addition, the presence of a tender enthesis is not necessarily indicative for underlying inflammatory disease as it could be related to overuse, metabolic disease or ageing. Therefore, we need a better way to identify the inflammatory component of entheseal involvement in psoriasis. To detect these inflammatory components in the entheses, ultrasound (US) examination can be used to identify inflammatory disease at the entheses. Objectives Our aims were to determine the prevalence of US abnormalities among psoriasis patients in primary care and to determine the concordance of clinical and US information at individual entheseal sites. Methods Adult patients with psoriasis were invited to participate in the SENSOR study. Patients who reported pain in joints, entheses or the lower back were eligible for clinical evaluation. If physical examination indicated a painful enthesis on the LEI/MASES or if arthritis was present, US examination of the entheses was performed. The six entheses of the Madrid Sonographic Enthesis Index (MASEI) and the lateral epicondyle tendon insertion (elbow) were evaluated according to the MASEI scoring system. Enthesitis was defined as US inflammation (positive power Doppler (PD) signal or a thickened enthesis of the plantar fascia) in combination with one clinical feature at the same enthesis. Structural changes detected by ultrasound were calcifications, increased thickness, irregular fibre structure and erosions. Results Of 524 patients who participated in the SENSOR study, 111 patients were assessed both by physical examination and by US. In 106 (95%) patients we detected US abnormalities. In 56 (50%) patients we found structural changes without indication for inflammatory disease. In 50 (45%) patients we found US abnormalities indicating inflammatory disease at the enthesis (positive PD: n=35; thickened plantar fascia: n=15). When we combined the US data with the clinical information, 36% of US inflammatory disease were confirmed [Figure 1]. Conclusions We found US abnormalities in 95% of the primary care psoriasis patients with musculoskeletal complaints, which is a combination of both structural and inflammatory US components. In 45% of primary care psoriasis patients we observed US inflammatory disease, which was confirmed in 36% of the patients by clinical information. Acknowledgements This study was financially funded by an investigator-initiated grant from Pfizer bv. Disclosure of Interest None declared

Modification of a sonographic enthesitis score to differentiate between psoriatic arthritis and young healthy volunteers

Objectives: We aimed to describe sonographic structural and inflammatory changes in entheses of patients with recently diagnosed psoriatic arthritis (PsA), patients with established PsA, and young healthy volunteers, and to investigate whether the MAdrid Sonographic Enthesitis Index (MASEI) enables us to distinguish these groups in an extreme comparison. Method: New and established PsA patients and healthy volunteers (aged 20–30 years) were recruited. The triceps, quadriceps, patellar, Achilles and elbow extensor tendon insertion, and plantar fascia entheses were investigated sonographically for structural changes, erosions, calcifications, increased thickness, bursitis, and power Doppler (PD) signal according to the MASEI. Results: The study included 25 new and 25 established PsA patients, and 25 healthy volunteers. Increased thickness and PD signal in knee entheses were common for patients and healthy volunteers, while changes at other locations predominantly occurred in patients only. PD was recoded (1, one spot; 1.5, two or three spots; 2, confluent signal; 3, severe confluent signal) and thickness of knee entheses excluded. This resulted in different modified MASEI scores between PsA patients and young healthy controls: median (interquartile range) modified MASEI of 13 (10–22.5) in new PsA, 13.5 (9.5–18) in established PsA, and 3 (1–8.5) in healthy volunteers (p = 0.002). Conclusions: Structural ultrasound changes and PD in entheses are common in both new and established PsA and healthy controls. MASEI score did not differentiate PsA patients from young healthy volunteers. After recoding of PD severity and excluding thickness of knee entheses, marked differences between PsA patients and healthy controls were observed.

SAT0103 Three-monthly ultrasound monitoring of rheumatoid arthritis patients tapering their medication has limited value in predicting disease relapse

Background Prognostic factors that may guide tapering decisions for DMARDs and TNFi on individual patient level are not available. To improve successful tapering subclinical synovitis may play a role in maintaining the remission state. Studies using ultrasound suggest that the presence of subclinical synovitis may elicit early disease relapse in remission. Objectives Our aim is to determine if ultrasound synovitis precedes disease relapse while tapering synthetic DMARD (sDMARD) or TNFi in patients with RA who achieved clinical remission on sDMARD and TNFi. Methods We included 125 RA patients (aged>17 years) treated with an sDMARD and a TNF-inhibitor who were in remission (DAS44≤2.4 & SJC≤1). Demographic characteristics, swollen and tender joints, laboratory variables and ultrasound synovitis (MCP2-5; PIP2-5; wrists; MTP2-5) were recorded at each visit (every three months) during one year follow-up. Patients were randomised to two tapering strategies: i) tapering sDMARD; ii) tapering TNFi. Disease relapse was defined as DAS44>2.4 or SJC>1. Ultrasound synovitis was defined as GS≤1 and/or PD≤0. To estimate whether ultrasound is able to identify patients who will have a disease relapse within three months follow-up a Cox proportional regression model for time to event data was used. Results: Ultrasound synovitis was found in 58% of RA patients in clinical remission. After one year follow-up 36% of RA patients had a disease relapse of whom 60% had ultrasound synovitis at baseline. table 1 shows the distribution of relapse en ultrasound synovitis for every three months. In the multivariate Cox model increasing number of joints with ultrasound synovitis was not significantly associated with disease relapse within three months follow-up (HR 1.21; 95%CI: 0.97-1.51) [table 2].Table 1 Distribution of disease relapse and US synovitis during follow-up, n (%) T0 T3 T6 T9 T12 US synovitis 72/125 (58) 60/124 (48) 62/112 (55) 40/96 (42) - Disease relapse 0 6/124 (5) 8/112 (7) 23/96 (24) 8/67 (12) US synovitis at previous visit - 4/6 (67) 5/8 (63) 14/23 (61) 6/8 (75) No disease relapse 0 118/124 (95) 104/112 (93) 73/93 (78) 59/67 (88) No US synovitis at previous visit - 46/118 (39) 47/104 (45) 23/73 (32) 29/59 (49) US = ultrasound Table 2 Multivariate Cox model with US synovitis or PD synovitis for disease relapse Model US synovitis HR (95% CI) Model PD synovitis HR (95% CI) Age 0.99 (0.97-1.02) 0.99 (0.97-1.02) Gender 1.08 (0.53-2.17) 1.05 (0.53-2.11) Time since diagnosis 1.02 (0.92-1.13) 1.03 (0.93-1.14) ACCP 0.47 (0.24-0.91) 0.51 (0.27-0.97) DAS (at time of US) 2.25 (1.21-4.19) 2.34 (1.25-4.41) US synovitis 1.21 (0.97-1.51) PD synovitis 1.35 (1.02-1.80) US = ultrasound; PD = power Doppler; HR = hazard ratio; ACCP=anti-cyclic citrullinated peptide antibody; DAS = disease activity score Conclusions Monitoring RA patients who started tapering their medication every three months showed limited value for ultrasound to identify patients who will have a disease relapse. Disclosure of Interest: None declared

THU0445 Validation of The Contest Questionnaires To Screen for Psoriatic Arthritis in Primary Care Psoriasis Patients

Background Various screening tools have been developed and validated over the years in order to enhance early recognition of psoriatic arthritis (PsA) among psoriasis patients, but their performance remains suboptimal. In 2014 the CONTEST-group developed a new screening tool consisting of the most discriminating questions from 3 existing tools (PEST, PASE, TOPAS) which was externally validated in 2 psoriasis cohorts from dermatology. Validation in a primary care setting has yet to be performed. Objectives To externally validate the CONTEST questionnaire in psoriasis patients in primary care. Methods Data from the SENSOR study was used, a cross-sectional study in adult psoriasis patients with regular spells of musculoskeletal complaints from primary care. In this study, patients completed the PEST and PASE screening-questionnaires before clinical evaluation. Within CONTEST 3 TOPAS questions are used that were not included in our study. These questions were therefore replaced by similar questions: ToPAS 2A was replaced by PEST 3, ToPAS 2B by nail assessment by a dermatologist and ToPAS 7 by data from the manikin in the PEST. We calculated sensitivity, specificity and area under the curve (AUC) for the CONTEST with a cutoff of 4, as well as the CONTEST-w (weighted version, cutoff of 8) and the CONTEST-jt (including the PEST manikin, cutoff of 5). Performance was also calculated selecting the patients in the same way as the CONTEST study, i.e. only inviting patients with a positive PEST and/or PASE questionnaire for clinical evaluation. As a reference standard we used a clinical diagnosis of PsA made by a rheumatologist and enthesitis confirmed by ultrasound (presence of Power Doppler). Results from our dataset were compared with data from the development cohort and with the performance of the PEST. Results For this analysis 473 psoriasis patients at risk for PsA were available. Compared with the development cohort sensitivity was considerably lower in our dataset (0.30–0.51) than in the development of the CONTEST (0.86). Specificity was higher in our dataset (0.75–0.87) compared with the CONTEST development (0.35–0.48). While AUCs were around 0.7 for all three versions, comparable with the AUCs found in the development of CONTEST. Comparing these results with the performance of the PEST in our population, it shows that the sensitivity is lower for the CONTEST (0.30–0.51) than for the PEST (0.68), while the specificity is slightly higher (0.75–0.87 vs 0.71). Conclusions External validation of the CONTEST questionnaire in primary care psoriasis patients with regular spells of musculoskeletal symptoms resulted in lower sensitivity and higher specificity compared to the development cohort, while AUCs were comparable. When only selecting patients with at least one positive screeningtool, the sensitivity slightly increases while the specificity slightly decreases. However, the performance of the CONTEST questionnaires does not seem to exceed the performance of the PEST in a primary care setting. Acknowledgement This study was financially funded by an investigator-initiated grant from Pfizer bv. Disclosure of Interest None declared

AB0968 High-Frame Rate Power Doppler Imaging Is More Sensitive than Conventional Power Doppler in Detecting Low Blood Flows in A Flow-Phantom and in Healthy Volunteers

Background Early detection of inflammation at diagnosis of rheumatoid arthritis (RA) or in remission of RA is important to optimise treatment in order to prevent joint damage and disability. Recent studies in ultrasound (US) indicate that US, especially power Doppler (PD), is more sensitive to detect inflammation than physical examination. Early diagnosis and treatment monitoring could be achieved by a more sensitive power Doppler (PD) method to detect early increased vascularisation. Inspired by recent breakthrough work in high-frame rate Doppler US imaging that was shown to be more sensitive to low flows associated with vascularisation [1], we systemically explored this method for its application in diagnosing and monitoring RA. Objectives (i) To compare the minimal flow velocity that can be detected with the high-frame rate Doppler US technique and a conventional clinical US machine using a flow phantom. (ii) To show visual differences between high-frame rate PDUS and conventional PDUS in healthy volunteers assuming that high-frame rate PDUS would detect more vascularisation in MCP2 joints. Methods In a flow phantom filled with tissue mimicking material [2] and a vessel diameter of 700 μm, we tested the PDUS performance of conventional PDUS (Esaote MyLab60) and a custom high-frame rate PD imaging technique (Verasonics Vantage). Settings for both methods were optimised to detect lowest flows (continuous PDUS signal) by adjusting pulse repetition frequency (PRF), velocity range, wall filters, frequency and gain. Subsequently we included six healthy volunteers and we performed conventional PDUS and high-frame rate PDUS of the MCP2 joint. The US images were graded on power Doppler (PD; 0–3) according to a semi-quantitatively scoring system of Naredo et al. Results In the flow phantom we could detect a flow velocity of 2.5 mm/s with the conventional PDUS. With the high-frame rate PDUS the lowest detectable flow was 0.5 mm/s. Results in healthy volunteers (n=6) showed no PD signal in MCP2 joints using conventional PDUS (Figure 1A). With high-frame rate PDUS (Figure 1B) the median PD grade was 2 (IQR: 2 - 2). Conclusions In a flow phantom we could detect five times lower flows with the high-frame rate PDUS technique than with conventional PDUS. Contrary to conventional PDUS, we detected a positive PD signal in all healthy volunteers with high-frame rate PDUS. Therefore, high-frame rate PDUS is more sensitive to vascularisation. Further evaluation whether this will facilitate early diagnosis and monitoring in RA is needed. References Mace E, Montaldo G, Cohen I, Baulac M, Fink M, Tanter M. Functional ultrasound imaging of the brain. Nat Methods. 2011 Aug;8(8):662–4. Ten Cate DF, Luime JJ, van der Ven M, Hazes JM, Kooiman K, de Jong N, et al. Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom. Arthritis Res Ther. 2013;15(5):R162. Disclosure of Interest None declared

SAT0572 Screening for PSA in Primary Care Psoriasis Patients with Musculoskeletal Complaints with Pest, Pase & Earp

Background Psoriatic Arthritis (PsA) is a progressive inflammatory joint disease that can lead to severe joint damage. New treatment strategies can be very effective in early stages of the disease [1]. This requires early recognition of the symptoms to be PsA. Several screening tools have been developed to enhance early recognition [1-4]. However, most were developed in secondary care [2,3], while early recognition should ideally take place in primary care. Objectives To evaluate the screening performance of the PEST [4], PASE [2,5] and EARP [3] to identify psoriatic arthritis among primary care psoriasis patients with recurrent spells musculoskeletal complaints (MSC). Methods We conducted a cross-sectional study in adult primary care patients with psoriasis who reported recurrent MSC spells. Patients were selected by ICPC code S91 for psoriasis and the presence of recurrent spells of MSC (joints, enthesis or low back pain) was determined by telephone interview. Patients completed the PEST, PASE & EARP questionnaires before clinical evaluation by a trained research nurse. Assessments included PASI, LEI/MASES, 66/68-joint count and the presence of nail-psoriasis. When patients reported a painful enthesis on LEI/MASES, an ultrasound of the entheses was performed. A PsA case fulfilled the CASPAR criteria. Sensitivity and specificity were determined for the PEST and EARP cut off ≥3 and PASE cut off ≥44 as well as ≥47. Results 473 psoriasis patients participated with a mean ± SD age of 55.7±13.9 years and 50.9% being male. Median PASI score was 2.3 (IQR 1-4) and 71 patients (15.0%) had nail abnormalities related to psoriasis. We found 17 new cases of PsA (3.6%) as diagnosed by a rheumatologist. Moreover, we found 36 cases of enthesitis, confirmed by ultrasound. The majority of these refrained from further evaluation by a rheumatologist, however most of them would classify as PsA according to the CASPAR criteria. Looking into all cases, including enthesitis, the EARP had a sensitivity of 87% and a specificity of 33%, for the PEST this was 68% and 71%. The PASE had a sensitivity of 66% and a specificity of 55% at the cut off of ≥44 and 59% and 64% at the cut off of≥47 (Table 2). Similar figures were observed if only axial manifestations and arthritis were taken into account. Conclusions Modest sensitivity was observed for the PEST and PASE with an acceptable specificity for the PEST, while the EARP had high sensitivity and low specificity, which is undesirable for screening. The performance of all screening tools was lower than previously reported in secondary care settings [1-4]. References Coates LC, et al. BMC Musculoskelet Disord, 2013. Husni ME, et al. J Am Acad Dermatol, 2007. Tinazzi I, et al. Rheumatology (Oxford), 2012. Ibrahim GH, et al. Clin Exp Rheumatol, 2009. Dominguez, PL, et al. Arch Dermatol Res, 2009. Acknowledgements This study was financially funded by an investigator-initiated grant from Pfizer bv. Disclosure of Interest None declared

AB0817 Prevalence of Musculoskeletal Complaints and Psoriatic Arthritis in Primary Care Patients with Psoriasis

Background Over 25% of the new consultations in primary care is due to musculoskeletal complaints (MSC)(1). In patient with psoriasis, the underlying diagnosis could be psoriatic arthritis (PsA). Prevalence figures of PsA in psoriasis patients vary widely (6-42%) and data in primary care is scarce (2, 3) Objectives To estimate the prevalence of MSC and PsA in primary care patients with psoriasis. Methods We conducted a cross-sectional study in adult primary care patients with psoriasis. Patients were identified from GP records by ICPC code S91 for psoriasis. Responding patients reporting pain in joints, entheses or the lower back were checked on eligibility by a telephone interview and invited for clinical evaluation. Ultrasonoghraphy (US) of the enthesis was performed if a patient had at least one tender enthesis (LEI/MASES) by an independent trained examiner. Patients were referred to a rheumatologist if clinical evaluation suggested the presence of arthritis or axial disease or ultrasonography of the enthesis showed positive Power Doppler (PD) signal. A PsA case was defined by opinion of the rheumatologist or fulfilling the CASPAR criteria with PD signal in an enthesis on US. Results 2564 psoriasis (PsO) patients from 97 GPs were invited. Of the 1673 responders (65.2%), 841 (50.3%) were willing to participate. 823 (32.1%) patients reported suffering from MSC of which eventually 524 were eligible and clinically evaluated. We identified 81 cases of PsA (Figure 1), of which 17 (21%) were newly diagnosed, leading to a prevalence of 3.2% (95%CI 2.5%>3.9%) among primary care psoriasis patients, assuming no additional cases of PsA among the non-responders. Besides these cases, we also identified 36 patients with enthesitis confirmed by ultrasound, which would increase the prevalence of PsA towards 4.6% (95% CI 3.8%>5.4%). Conclusions Among psoriasis patients in primary care the prevalence of PsA is estimated to be 3.2%, which would increase towards 4.6% if you take the enthesitis cases into account. Moreover, 21% of the cases was newly diagnosed. We hereby assumed that no additional cases would be observed in the non-responders. The prevalence of MSC is estimated to be 32.1%, which is comparable with the prevalence in general population (1). References van der Linden MW et al., NIVEL/RIVM2004. Ibrahim G. et al, Arthritis Rheum. 2009. Gelfand JM. et al, Arch Dermatol. 2005 Acknowledgements This study was financially funded by an investigator-initiated grant from Pfizer bv. Disclosure of Interest None declared

SAT0491 Comparing the Power Doppler Modality of 5 Ultrasound Machines using a Microvessel Flow Phantom

Background In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS).[1-3] However, in our experience, PDUS may be highly dependent on machine type. To clarify how the PDUS signal differs between machines a flow phantom could be used. Objectives Determine the lowest flow that the power Doppler (PD) modality of 5 US machines could detect by creating a small microvessel (150micron) flow phantom. Methods The flow phantom, consisted of an acrylic (PMMA) container filled with tissue mimicking material(TMM)[4], with three microvessels (2000 micron, 1000 micron and 150 micron). The blood mimicking fluid was based on the recipe by Ramnarine.[5] A syringe pump (Harvard Apparatus Pump 11 Elite) was used to generate different flows. Five US machines were used, the Esaote MyLab60 (probe LA 435), Aloka α7 (UST-5411), Philips iU22 (L9-3), Ultrasonix SonixTouch (L14-5/38) and VisualSonics Vevo2100 (MS200). Settings were optimised to detect lowest flows by adjusting pulse repetition frequency, velocity range, filters, frequency and gain. We recorded the lowest possible flow in each of the vessels that still resulted in a continuous PDUS signal for each machine. Flow velocities were calculated from pump flow setting and microvessel diameter. Results Conclusions PD was highly variable between machines. The Esaote detected the lowest flow. The very low flow detected by the Esaote in the 2mm vessel was checked multiple times by multiple observers. The machines predominantly used in research (Ultrasonix, VisualSonics) were not able to detect flows in the smallest vessel (150 micron). The differences found between the machines are apparently caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Probe frequency does not explain the large differences found. A spurious finding was that the minimal detectable flow velocity was lower in the 1mm vessel than in the 2mm vessel. Possibly, the 1mm vessel was compressed by the TMM so that the calculated flow velocity was underestimated. The relative differences between machines are unchanged by this. For a reliable and reproducible detection of microvessel flow in inflamed joints, the choice of the US machine and its settings seems very important. By investigating the flow velocity of blood in an inflamed joint, the minimal flows that rheumatological US machines need to detect will be known. Then, our flow phantom would be a very useful instrument in the process of optimising US machines and for rheumatologists when buying a new US machine. References Peluso (2011) Ann Rheum Dis Saleem (2011) Ann Rheum Dis Brown (2008) Arthritis Rheum Teirlinck (1998) Ultrasonics Ramnarine (1998) Ultrasound Med Biol Disclosure of Interest None Declared