T. Uehara

Ultrasonography is a potent tool for the prediction of progressive joint destruction during clinical remission of rheumatoid arthritis

ObjectivesAlthough “clinical remission” has been a realistic goal of treatment in rheumatoid arthritis (RA), there is evidence that subclinical synovitis is associated with ongoing structural damage even after clinical remission is achieved. In the study reported here, we assessed whether ultrasonography (US) can predict progressive joint destruction during clinical remission of RA.MethodsThirty-one patients with RA in clinical remission based on the disease activity score in 28 joints were recruited for this study. Bilateral wrists and all of the metacarpophalangeal and proximal interphalangeal (PIP) joints were examined by power Doppler (PD) ultrasonography (US), and the PD signals were scored semiquantitatively in each joint. The total PD score was calculated as the sum of individual scores for each joint.ResultsAmong 22 RA patients who maintained clinical remission during the 2-year follow-up period, seven showed radiographic progression. Radiographic progression was strongly associated with total PD score at entry, with all patients showing radiographic progression having a total PD score of ≥2 at entry and none of the patients with a total PD score of ≤1 showing any radiographic progression. There was no significant association of therapeutic agents with progressing or non-progressing cases.ConclusionsPD-US detects synovitis causing joint destruction even when the patient is in clinical remission. Thus, remission visible on US is essential to reach “true remission” of RA.

Deep-inspiration breath-hold 18F-FDG-PET/CT is useful for assessment of connective tissue disease associated interstitial pneumonia

Abstract Objective: To examine clinical utility of 18F-flurodeoxyglucose (FDG)-positron emission tomography (PET)/CT for assessment of interstitial lung disease (ILD) in patients with connective tissue diseases (CTDs). Methods: A total of 69 18F-FDG PET/CT scans were conducted under deep inspiratory breath hold (DIBH) conditions in 45 CTD patients with ILD, including 16 dermatomyositis/polymyositis, nine systemic scleroderma and seven rheumatoid arthritis. Intensity and distribution of 18F-FDG signals in PET/CT were determined by standardized uptake value (SUVmax) and visual score in 18 regions, respectively. ILD was defined as active when immunosuppressive therapy was initiated or intensified. Results: Both SUVmax and visual score were higher in active phase (n = 32) than inactive phase (n = 37) (both p < 0.05), regardless of the underlying CTD and plain CT findings. The both parameters reduced after initiating or intensifying treatment in the follow-up study of 17 active patients except two died patients who showed increased visual score. Another two died patients showed high visual score (15 and 6/18, respectively). Changing ratio of visual score, but not SUVmax was correlated with KL-6 (r2 = 0.38, p < 0.05) and CRP (r2 = 0.52, p < 0.05). Conclusion: The DIBH 18F-FDG PET/CT procedure sensitively illustrates active ILD lesions in CTD and the extended signal distribution is associated with unfavorable clinical outcome.

THU0408 Deep inspiratory breath hold PET/CT is useful for monitoring of activity in rheumatic disease associated lung interstitial pneumonitis

Objectives This study examined contributions of deep inspiratory breath hold (DIBH) -FDG-PET/CT to clinical assessment of ILD in collagen diseases. Methods We assessed ILD in 45 patients with collagen diseases including 6 RA, 9 SSc, and 17 DM/PM by using DIBHPET/CT. Distribution of positive signals was evaluated in the upper slice 2cm above the tracheal bifurcation, the middle slice 1 cm below the bifurcation, and the lower slice 2 cm above the right diaphragm. Individual slices were further divided into 6 regions. Visual score was determined by numbers of positive signal lesions in total 18 regions. Results Abnormal accumulation of FDG was found in the active ILD lesions which were concordant with nodular, reticular, consolidative shadows and ground glass opacity illustrated by plain CT scan. The visual score in the lesions was well correlated with serum levels of KL-6 (Pearson ρ=0.571, P=0.011) and CRP (Spearman ρ=0.506, P=0.016). The value was significantly higher in 26 patients who were judged as being clinically active than the other 19 patients. Of 24 patients who had follow-up examinations, abnormal FDG accumulation was reduced in response to the therapies in 11 patients, whereas the findings were unchanged or deteriorated in the remaining 13 patients who had stable or progressive ILD. In spite of no interval change in plain CT scan, PET/CT detected significant changes of FDG intensity in the follow-up studies in 5 patients. FDG signal was reduced in 4 of them, whereas it was increased in one patient. Conclusions In summary, DIBH PET/CT is useful for monitoring of activity in collagen disease associated ILD. Disclosure of Interest None Declared

FRI0065 Residual power doppler signals during clinical remission determine joint prognosis in rheumatoid arthritis

Background “Clinical remission” has been a realistic goal of treatment in rheumatoid arthritis (RA). However, there is evidence that subclinical synovitis is associated with progression of structural damage even after achieving clinical remission,12 which could reflect the inadequate sensitivity of the conventional clinical approaches to detect synovitis. Objectives Here we prospectively assessed RA patients in clinical remission to clarify whether ultrasonography (US) can predict long-term radiographic progression during persistent clinical remission. Methods Twenty-seven RA patients in clinical remission (DAS28-ESR <2.6 or DAS28-CRP <2.3) were recruited. Bilateral wrists, and all of MCPs and PIPs were examined by power Doppler (PD) US. Gray scale (GS) and PD signals were scored in each joint from 0 to 3, respectively. Total PD score and total GS score were calculated by summing up the score of individual joints. Hand X-ray was performed at entry and at 2 years. Patients were defined as radiographically progressing cases when the change of the van der Heijde-modified total Sharp score exceeded 0.5 units per year and the others were as non-progressing cases. In principle, therapy was not modified during the study, unless the patients had clinical flare-up. Results Twenty-two patients maintained clinical remission during the 2-year follow-up, while 5 had clinical flare-up. The persistent remission group was further divided into 7 progressing cases (32%) and 15 non-progressing cases (68%) based on X-ray findings. There was no significant difference in age (51.4±7.74 vs 59.2±12.1 years, p =0.15) and disease duration (7.3±3.9 vs 6.7±3.7 years, p =0.74) at entry between the two groups. Progressive radiographic destruction was strongly associated with total PD score at entry, but not with total GS score. Progressive radiographic destruction in any joints was found in 7 of 11 patients (64%) having more than 2 of total PD score at entry, but none of the other 11 having PD score 0 or 1. There was no significant association of therapeutic agents with radiographic progressing. When the persistent clinical remission group was further divided into 12 TNF inhibitor (TNFi)-free and 10 TNFi-treated cases, total PD score was significantly higher in patients with radiographic progression than in those without progression in both the TNFi-free (2.75±0.83 vs 0.63±0.86, p =0.0039) and TNFi-treated groups (10.3±7.93 vs 1.14±1.36, p =0.029). However, no significant difference was found in radiographic progression between the TNFi-free and TNFi-treated groups when these are compared in the same total PD score categories. Conclusions PDUS detects latent synovitis causing joint destruction even in the clinical remission of RA patients, irrespective of TNFi therapy. Thus, US is a potent tool for prediction of joint prognosis during clinical remission of RA. References Mulherin D, Fitzgerald O, Bresnihan B. Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ. Br J Rheumatol 1996;35:1263-8. Molenaar ET, Voskuyl AE, Dinant HJ, et al. Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum 2004;50:36-42. Disclosure of Interest None Declared

SAT0519 Total Power Doppler Score-8 is a Useful Diagnostic Marker of Musculoskeletal Ultrasonography for Screening and Activity Measurement of Rheumatoid Arthritis

Background Musculoskeletal ultrasonography (US) has been shown to be helpful for diagnosis and monitoring of rheumatoid arthritis (RA). Although several joint combinations have been demonstrated to be useful in the assessment of RA,1 2 there is still no consensus in defining the joints to evaluate. As comprehensive evaluation by US in RA is time consuming and not feasible in daily practice, it is important to determine the optimal combinations of minimal number of joints. Objectives Here we investigated the optimal number and combination of joints to be assessed by power Doppler (PD) US in RA. Methods PDUS were performed in 24 joints, including all PIP, MCP, bilateral wrist and knee joints, as comprehensive evaluation in 231 patients with RA. PD images were scored semiquantitatively from 0 to 3 in each joint, and total PD score-24 was calculated as the sum of scores of 24 joints. The patients were divided into PD-positive (total PD score-24 ≥ 1) and PD-negative (total PD score-24 = 0) groups. The sensitivity and negative predictive value (NPV) of sum scores of different joint combinations were evaluated. The correlations between total PD score-24 and each joint score or the different sum scores were also assessed. Results The averages of PD scores were high in bilateral wrist, knee, MCP 2 and 3 joints, while these were low in other MCP and all PIP joints. Higher correlation coefficients were found between total PD score-24 and PD scores of bilateral MCP 2, 3 and wrist joints, whereas correlations between total PD score-24 and PD scores of bilateral knee and all PIP joints were weak. Among the sum PD scores of different joint combinations, sum score of reduced 8 joints (total PD score-8), including bilateral MCP 2, 3, wrist, and knee joints, showed the highest sensitivity and NPV (table 1; 98% and 96%, respectively). Moreover, total PD score-8 showed very high correlation with the total PD score-24 (rs = 0.97, P < 0.01). Conclusions This study shows that the total PD score-8 has almost the same level of sensitivity as the comprehensive evaluation and correlates well with the comprehensive evaluation. Thus total PD score-8 is simple and useful enough for screening and activity measurement for RA. References Perricone C, Ceccarelli F, Modesti M, et al. The 6-joint ultrasonographic assessment: a valid, sensitive-to-change and feasible method for evaluating joint inflammation in RA. Rheumatology (Oxford) 2012;51:866-73. Ohrndorf S, Fischer IU, Kellner H, et al. Reliability of the novel 7-joint ultrasound score: results from an inter- and intraobserver study performed by rheumatologists. Arthritis Care Res (Hoboken) 2012;64:1238-43. Disclosure of Interest None Declared

THU0171 Therapeutic response of lupus nephritis based on pathological findings in yokohama city university hospital

Background ISN/RPS classification of lupus nephritis was popular and reliable classification because of its semi-quantitativity of glomerular changes. However, tubulointerstitial involvement and the grade of glomerular sclerosis and of hyaline thrombi which could be poor prognostic factors, were not fully evaluated in this classification. Objectives To clarify the relationship between pathological evaluation and therapeutic response in lupus nephritis (LN). Methods According to ISN/RPS classification, samples of renal biopsy (RBx) from 51 patients with LN (35.1 y.o, 46 females) were evaluated. Tubulointerstitial involvement (TII), thorombi and glomerular sclerosis were also assessed. Treatment response at 6 months, 1, 2 and 5 years were evaluated by SLICC renal activity and response index score. Results Biopsy specimens included 19.5 glomeruli at average, though less than 10 glomeruli were found in 17.6%. The RBx samples were classified into ClassI/II/III/IV/V/VI (1/5/10/26/9/0). TII, thrombi and glomerular sclerosis were found in 60.8%, 21.6% and 58.8% of the specimens, respectively. These findings were negatively correlated with complete response (CR) rate. The existence of TII and glomerular sclerosis significantly influenced the CR rate at 6 onths. The finding of thrombi was a significant poor prognostic factor identified at 2 years. Corticosteroids (CS) and cyclophosphamide (CY) was chosen as the first line agents as the induction therapy. Initial dose of CS was increased with higher frequency of pulse therapy against Class III and IV after 2004. Similarly, intravenous infusion with CY was more frequently used for Class III, IV and V after 2004 than before. Complete response rate at 2 years was 70.0% and 46.2% in class III and IV, respectively. Table 1. Complete remission rate and Pathological findings 6 Months 1 Year 2 Years 5 Years + – + – + – + – TII 41.9%* 75.0% 53.3% 68.4% 65.4% 87.5% 41.7% 75.0% Thrombi 45.5% 57.5% 54.5% 60.5% 37.5%* 82.3% 40.0% 60.0% Glomerular sclerosis 43.3%* 71.4% 50.0% 71.4% 69.6% 77.8% 33.3% 72.7% *Showed a significant difference between two groups using chi-square analysis. Conclusions Tubulointerstitial involvement and glomerular sclerosis might reflect the response of an induction therapy. Thrombi might influence long-term treatment outcome. References Petri M, et al. Arthritis Rheum 2008;58(6):1784-1788 Disclosure of Interest None Declared

SAT0520 Ultrasonography is Useful for Predicting Boolean Remission after Achieving DAS28-Based Clinical Remission of Rheumatoid Arthritis

Background Although “clinical remission” has been a realistic goal of treatment in rheumatoid arthritis (RA), its definition is still controversial. In fact, progressive joint destruction is often observed even during persistent DAS28-based remission,1 2 suggesting that the criteria are not satisfactory for target of treatment. There is accumulating evidence that ultrasonography (US) is helpful for judgment of the disease remission. Objectives Here we investigated whether US can predict Boolean remission in RA patients who had been satisfied with DAS28-based remission criteria. Methods Twenty-seven RA patients who had been in DAS28-based clinical remission (DAS28-ESR < 2.6 or DAS28-CRP < 2.3) for more than 2 months were recruited and monitored for 2 years. Excluding patients having clinical flare-up during the study, the remaining patients were divided based on Boolean remission criteria at 2 years. Bilateral wrists and all of MCPs and PIPs were examined by Gray scale (GS) and power Doppler (PD) US at the entry. GS and PD signals were scored in each joint from 0 to 3, respectively. Total GS score and total PD score were calculated by summing up the score of individual joints. Hand X-ray was evaluated by van der Heijde-modified total Sharp score (mTSS) at the entry and end of study. Results Five patients dropped out of the study due to clinical flare-up, while DAS28 remission had been maintained for 2 years in 22 patients, including 16 patients (73%) who met Boolean remission criteria at the end of study. Both total GS score and total PD score at baseline were significantly lower in Boolean remission group than non-remission group (7.75 ± 6.02 vs 16.0 ± 11.3, p = 0.012, and 1.06 ± 1.14 vs 6.33 ± 6.99, p = 0.020, respectively). There was no significant difference in other baseline parameters, including duration of disease, duration of remission, mTSS, and disease activity composite parameters between the two groups. The cut-off values for total GS and PD scores calculated from the ROC curves were total GS scores > 7 and total PD scores > 2. The area under the ROC curves for total GS and PD scores were 0.82 (95% CI = 0.60 to 0.95, p = 0.0004) and 0.82 (95% CI = 0.60 to 0.95, p = 0.013). Among the factors for Boolean remission criteria at 2 years, high patient global assessment score was associated with high total GS score at the entry, while high swollen joint count was related to high total PD score. On the other hand, progression of mTSS was associated with high total PD score, but not with total GS score, at the entry. Conclusions This study shows that none or low grade of GS and PD findings in US are associated with the achievement of Boolean remission in near future. Thus, US is essential for assessment and prediction of “deeper remission” of RA. References Mulherin D, Fitzgerald O, Bresnihan B. Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ. Br J Rheumatol 1996;35:1263-8. Molenaar ET, Voskuyl AE, Dinant HJ, et al. Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum 2004;50:36-42. Disclosure of Interest None Declared

THU0448 The Profile of Musculoskeletal Ultrasonography in Patients with Adult Onset Still Disease.

Background Adult onset Still disease (AoSD) is a systemic inflammatory disease and characterized by daily spiking high fevers accompanied by a rash, arthritis, and systemic manifestations. The clinical course of AoSD can be divided into three patterns; monophasic pattern, polycyclic pattern, and chronic articular pattern. Especially in chronic articular pattern, patients may have severe, destructive arthritis. Although chronic articular pattern was mimicking RA, there was a few reports that mentioned about the finding of musculoskeletal ultrasonography of AoSD. Objectives To examine the profile of musculoskeletal ultrasonography (MSUS) in patients with AoSD. Methods Twenty-seven cases of 20 patients with AoSD were enrolled, who consulted to our department between 2003 and 2012. Laboratory data, physical findings, and medication were collected. Using MSUS, semi-quantitative evaluation by gray scale and power Doppler were performed. Results There are 35 patients with adult onset Still disease in our department (10 male and 25 female). Median age of onset was 49.5. The proportion of clinical course was as about as follows; monophasic 22.2%, polycyclic 55.6%, and chronic articular 22.2%, respectively. On the background of MSUS, 10 cases were male and 17 cases were female. The onset age was 57.5 years old (median). The positive rate of CRP, ferritin, and LDH was 81.0%, 93.3%, and 29.4%, respectively. In MSUS, the positive rate of GS was 34.8% in MCP, 26.2% in PIP, 50.0% in hand, and 20.7% in knee joints respectively. The positive rate of PD was 19.0%, 5.8%, 42.6%, and 22.4%, respectively. The average of GS score was 1.1±0.1, 0.8±0.1, 1.3±0.2 and 0.7±0.1, respectively. The average of PD score was 0.5±0.1, 0.2±0.1, 1.1±0.1, and 0.1±0.1, respectively. Coefficient of correlation between ferritin and GS score of hand joints was higher than other joints (0.424). Correlation between ferritin and PD score of hand joint was also higher than other joints. Image/graph Conclusions The positive rate of GS was higher than PD in patients with adult onset Still disease. GS and PD signals were frequently observed in hand joints and were correlated with the level of ferritin. Disclosure of Interest None Declared

SAT0403 Ultrasound in the diagnosis of rheumatoid arthritis

Background A comprehensive diagnosis of rheumatoid arthritis (RA) is made on the basis of immunological and morphological abnormalities. However, the 2010 American College of Rheumatology (ACR) – European League Against Rheumatism (EULAR) RA classification criteria depend heavily on serological markers and not morphologic imaging findings. Objectives We assessed the role of ultrasound (US) in the diagnosis of early RA when the new criteria were applied clinically. Methods We studied 128 patients who first visited our department with arthralgia. We categorized the patients into two groups based on clinical outcome 1 year later: patients treated with anti-rheumatic therapies were placed in the RA group, and the remaining patients constituted the non-RA group. Ten joints (bilaterally, the second and third MCPs and second PIPs of the fingers, wrists and knees) were evaluated at study entry by using gray-scale (GS) and power Doppler (PD), with semi-quantitative grading from 0 to 3. Total GS and PD scores (i.e. the sums of the grades in the 10 joints) were also compared. We also examined whether individual patients met the 1987 ACR RA classification criteria and the 2010 ACR/EULAR criteria. Results Anti-rheumatic drugs, including methotrexate and salazosulfapyridine, were initiated in 54 patients (RA group). The remaining 74 (non-RA group) consisted of 24 (32.4%) with undifferentiated arthritis, 13 (17.5%) with osteoarthritis, and the remainder with other diseases. At entry, 48 of the 54 RA patients (88.8%) fulfilled the 2010 ACR/EULAR criteria, whereas only 36 of 54 patients (66.7%) fulfilled the 1987 ACR criteria. Clinical findings and US findings at entry were compared between the two groups. Compared with the non-RA group, the RA group had significantly greater numbers of swollen and tender joints, significantly greater serum levels of C-reactive protein, and significantly higher frequencies of rheumatoid factor (RF) and anti-cyclic-citrullinated-peptide (CCP) antibody positivity (p<0.01). The proportion of patients with abnormal findings and the total GS and PD scores on US were also significantly higher in the RA group (P<0.05 and P<0.01, respectively). In all 6 patients in the RA group who did not meet the 2010 ACR–EULAR criteria at entry, active synovitis was proven by US. In contrast, one patient who had no proven synovitis on US and who was classified into the non-RA group, despite high titers of both RF and anti-CCP antibody, did not develop clinical manifestations of RA during the observation period. Conclusions US is useful for the diagnosis of RA, especially in patients without disease-associated autoantibodies. Its use may also help to avoid unnecessary treatment of patients with positive serological markers but no synovitis. Our findings suggest that US provides morphological information that is essential for the diagnosis of RA but is not included in the new criteria. Disclosure of Interest None Declared