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Disseminated nontuberculous mycobacterial infection (DNTM) is typically observed in immunocompromised hosts. Recently, it has been reported that healthy individuals with serum neutralizing autoantibodies for interferon (IFN)-γ can also develop DNTM. We herein report a case of anti-IFN-γ antibody-seropositive DNTM caused by Mycobacterium kansasii with symptoms mimicking TAFRO or POEMS syndrome, including anasarca, organomegaly, skin pigmentation, polyneuropathy, osteosclerotic change, thrombocytopenia, serum M protein, high C-reactive protein level, and reticulin fibrosis. The combination of antimicrobial chemotherapy with glucocorticoid and intravenous immunoglobulin improved his symptoms. Glucocorticoids may be an effective method of suppressing the production of anti-IFN-γ antibodies in DNTM.

Optic perineuritis (OPN), which is an inflammatory disorder affecting the optic nerve sheath, is one of the rare complications in granulomatosis with polyangiitis (GPA). Although several groups have reported that immunosuppressive therapies are generally effective against GPA-associated OPN, so far, there is little information as to other options for refractory cases. Here we demonstrate a case of GPA-associated OPN, which is refractory to potent immunosuppressive therapy including high-dose glucocorticoid, intravenous cyclophosphamide and rituximab therapy, and effective application of therapeutic plasma exchange. We also report here that CSF IL-6 levels may serve as a new biomarker for GPA-associated OPN.

Haemophagocytic syndrome (HPS) is one of the most severe complications of systemic lupus erythematosus (SLE). Although corticosteroids are usually selected as an initial treatment, some patients are corticosteroid-resistant and require additional immunosuppressants. Here, we report a case of SLE-associated HPS patient who was resistant to prednisolone, calcineurin inhibitors, cyclophosphamide, plasma exchange and infliximab but was successfully treated with mycophenolate mofetil (MMF). MMF could be an alternative treatment for intractable HPS complicated with SLE.

AIM To determine characteristics of rheumatoid arthritis (RA) patients in Japan who received the same biological disease-modifying antirheumatic drugs (bDMARDs) for at least 6 months and to identify factors associated with successful down-titration of bDMARDs dependent on shared decision-making. METHODS We included consecutive RA patients who received the same bDMARD with low disease activity or remission for at least 6 months in our two university hospitals. Patients treated with the bDMARD standard dose were defined as SD, while those treated with bDMARD down-titration were defined as DT. We retrospectively reviewed clinical charts and compared data between the two groups. RESULTS Of 288 patients with RA, 204 (70.8%) and 84 (29.2%) continued standard dose treatment and underwent down-titration treatment, respectively. Sixty-six of 84 (78.6%) down-titration-treated patients continued to show low disease activity or remission, whereas 18 (21.4%) relapsed 18.9 ± 24.4 months after bDMARD down-titration was started. Univariate predictor analysis showed that the probable factors of down-titration were no history of bDMARD treatment (P = .001) and low initial Disease Activity Assessment of 28 joint score (P = .048). Other clinical characteristics had no significant relationship with successful down-titration. CONCLUSIONS Thus, bDMARD-naive patients and those with low initial disease activity are more likely to agree to attempt down-titration. However, the timing and method of down-titration should be made in shared decision-making between patients and rheumatologists.

TRIM21 is an E3 ubiquitin ligase for interferon regulatory factors (IRFs) that are involved in innate and acquired immunity. Here, we evaluated the role of TRIM21 in the interferon (IFN) signature of systemic lupus erythematosus (SLE).Twenty SLE patients and 24 healthy controls were enrolled in this study. We analyzed mRNA expression of TRIM21, type I IFN, and IFN-inducible genes in peripheral blood mononuclear cell (PBMC). The protein levels of IRFs were assessed by Western blotting in PBMCs cultured with or without MG-132.The expression of TRIM21 mRNA and protein was significantly higher in SLE PBMCs as compared to healthy controls. There was a correlation between TRIM21 mRNA expression and SLE activities. In contrast to a negative correlation between mRNA expression level of TRIM21 and those of type I IFNs in healthy controls, we found a positive correlation between them in anti-TRIM21 antibody-positive SLE patients. Neither positive nor negative correlation was observed in the autoantibody-negative SLE patients. Western-blotting analysis revealed impaired ubiquitin-dependent proteasomal degradation of IRFs in SLE PBMCs.Our study showed ubiquitin-dependent proteasomal degradation of IRFs was impaired in anti-TRIM21 antibody-dependent and -independent fashions, leading to amplification of IFN signature in SLE.

Background Interstitial lung disease (ILD) is the principal cause of death in polymyositis/dermatomyositis (PM/DM). Here we investigated prognostic factors for death and serious infection in PM/DM-ILD using the multicenter database. Methods We retrospectively reviewed baseline demographic, clinical and laboratory findings, treatment regimens and outcomes in patients with PM/DM-ILD. The distribution of ILD lesions was evaluated in four divided lung zones of high-resolution computed tomography images. Results Of 116 patients with PM/DM-ILD, 14 died within 6 months from the diagnosis. As independent risk factors for early death, extended ILD lesions in upper lung fields (odds ratio (OR) 8.01, p = 0.016) and hypocapnia (OR 6.85, p = 0.038) were identified. Serious infection was found in 38 patients, including 11 patients who died of respiratory or multiple infections. The independent risk factors were high serum KL-6 (OR 3.68, p = 0.027), high initial dose of prednisolone (PSL) (OR 4.18, p = 0.013), and combination immunosuppressive therapies (OR 5.51, p

The demographic data of patients with PM/DM with ILD. (PDF 37 kb)

Comparison of demographic data between PM/DM-ILD patients with or without complication of serious infection. (PDF 92 kb)

Comparison of demographic data among each PM/DM subtype in PM/DM-ILD patients. (PDF 102 kb)

Background Interstitial lung disease (ILD) and concomitant infectious diseases are the predominant causes of death in polymyositis/dermatomyositis (PM/DM). We have already reported that hypocapnea and ILD lesion in upper lung fields are independent prognostic factors. Micro RNA is a non-coding RNA, which has a certain function such as transcriptional regulation. miR-1 has been reported to be associated with myocyte differentiation and to decrease in muscle tissue from patients with inflammatory myopathies. Objectives Here we investigated the association of serum miR-1 level with clinical course of PM/DM-associated ILD (PM/DM-ILD). Methods We retrospectively analyzed clinical baseline, serum miR-1 level, initial therapeutic regimens, total amounts of PSL, clinical outcomes, and episode of infection of patient with PM/DM-ILD who had received initial treatment at six hospitals associated with Yokohama City University from 2003 to 2016. The serum miR-1 level was measured by quantitative real-time PCR. Results One hundred sixteen (PM 22, DM 51, and clinically amyopathic DM 43) patients were included. The mean age was 56±15 years and 83 were female. As initial therapies, oral PSL, methylprednisolone (mPSL) pulse, intravenous cyclophosphamide (IVCY), and oral calcineurin inhibitor therapies were performed in 113 (97%), 80 (69%), 48 (41%) and 80 (69%), respectively. Forty-one patients had a serious infection at 51±38 days from initiation of immunosuppressants and 10 died of infections. Old age, low PaCO 2 and albumin, high LDH and KL-6, high score of ILD, high initial dose of PSL, mPSL pulse, IVCY, calcineurin inhibitor and combination therapy were extracted as risk factors for infection by univariate analyses. A multivariate logistic regression analyses revealed that combination therapy ( p =0.012, OR 2.83), old age ( p =0.024, OR 2.12), high initial dose of PSL ( p =0.024, OR 2.69), low albumin ( p =0.031, OR 3.56), and low PaCO 2 ( p =0.038, OR 2.67) were independent risk factors for infection. Serum samples were obtained from total of 14 patients and 13 healthy controls. Serum miR-1 levels in PM/DM-ILD patients before treatment were significantly higher than those in healthy controls ( p =0.047). Also serum miR-1 levels were significantly higher in PM/DM-ILD patients with concomitant infectious diseases as compared to patients without infectious diseases ( p =0.043). We further divided the PM/DM-ILD cases into two groups by the serum miR-1 level. The higher miR-1 group showed poorer effectiveness of ILD treatment ( p =0.040), and lower lymphocyte count ( p =0.013) as compared to the lower miR-1 group. Conclusions Appropriate monitoring is important for PM/DM-ILD, especially in older patients with malnutrition or decreased respiratory function. miR-1 can be a new biomarker for predicting treatment response and concomitant infectious diseases during treatment for PM/DM-ILD. References Robert W. Georgantas et al, Inhibition of myogenic microRNAs 1, 133, and 206 by inflammatory cytokines links inflammation and muscle degeneration in adult inflammatory myopathies, Arthritis Rheum, 2014;66:1022–33. Disclosure of Interest None declared

Background Although recent development of a variety of biologics has dramatically improved treatment for rheumatoid arthritis (RA), it is still unclear which biologics is better for use in each patient. Some previous studies have shown the predictive factors for good response (GR) to tocilizumab (TCZ), including low HAQ, high DAS281), low levels of serum soluble IL-6 receptor2), and low numbers of previous use of other biologics3). However, the consensus is not immediately available. Objectives To compare continuation rates (CR) of TCZ by the responsiveness to the therapy and to identify predictive factors for GR to TCZ in RA. Methods Patient with RA who newly started receiving TCZ after April 2008 in our hospital, were included in the study. We collected patient records, medication histories, laboratory data, and clinical parameters longitudinally after starting TCZ. Statistical analyses were performed using the chi-square test, binomial logistic regression analysis, Kaplan-Meier method, and the log-rank test. Results Ninety-two patients were included in the study. The mean age and disease duration at baseline were 60.0±13.5 years and 8.7±8.0 years, respectively. The seroprevalence of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor were 95.4% and 95.7%, respectively. The rate of methotrexate and prednisolone at baseline were 45.7% and 64.1%, respectively. TCZ was administered as the first biologic in 42 patients, and as the second biologic in 33. DAS28(ESR) and CDAI revealed high disease activity at baseline (5.2±1.5 and 25.4±14.1, respectively). The mean CR of all patients was 42.1±4.0 months. The CR was significantly higher in patients who achieved GR in EULAR response criteria at 6 months after starting TCZ than those who did not achieve GR (54.0±6.0 months vs 29.0±5.3 months, p=0.004). Multivariate statistical analysis revealed two predictive factors for achieving GR at 6 months after starting TCZ, the low number of previous use of other biologics and the low CDAI at baseline (p=0.018, odds ratio (OR) =0.386, and p=0.011, OR=0.944, respectively). We divided the patients into two groups, patients using TCZ as the first biologic and patients using it as the second biologic. Univariate statistical analyses revealed low usage rate and dose of prednisolone (PSL) and low serum creatinine level at baseline as the predictive factors for achieving GR in patients using TCZ as the first biologic, and low DAS28(ESR), CDAI and HAQ-DI in the patients using TCZ as the second biologic. By multivariate statistical analysis, we identified the low CDAI as a predictive factor in the patients using TCZ as the second biologic. Conclusions RA patients who achieved GR at 6 months after starting TCZ showed higher CR than the others. This study also suggests that low number of biologics usage and low CDAI at baseline are the predictive factors for GR. The history of biologics usage may be important to identify the predictive factors for GR to TCZ. References Ann Rheum Dis 2011;70:1216–22. Ann Rheum Dis 2014;73:945–7. Pharmacological Research 2016;111:264–71. Disclosure of Interest None declared

To investigate the optimal number and combination of joints to be assessed by power Doppler ultrasonography (PDUS) in daily practice for rheumatoid arthritis (RA).PDUS were performed in 24 joints, including all proximal interphalangeal, metacarpophalangeal (MCP), and bilateral wrist and knee joints in 234 patients with RA. PD signals were scored semiquantitatively from 0 to 3 in each joint, and total PD score-24 was calculated by summing them up as comprehensive assessment.Positive PD signals were more frequently found in bilateral wrist, knee, and the second and third MCP joints than the other joints. The individual PD scores of these 8 joints also showed higher correlation coefficients with total PD score-24 (rs ≥ 0.4). Among the sum PD scores of various selected joint combinations, the score of the combination of 8 joints (total PD score-8), including bilateral second and third MCP, wrist, and knee joints, showed the highest sensitivity and negative predictive value (98.1% and 96.2%, respectively). Total PD score-8 showed high correlation with the total PD score-24 (rs = 0.97, p0.01).Total PD score-8 is simple and efficient enough for monitoring disease activity and judging imaging remission of RA in daily practice.

Multifocal fibrosclerosis (MFS), which causes systemic and chronic connective tissue inflammation, has been associated with IgG4 and regarded as an identical entity with "IgG4-related disease (IgG4-RD)". Although a few cases of MFS mimicking IgG4-RD histopathologically, despite the absence of a serum IgG4 elevation and IgG4-positive plasma cell infiltration, have been reported, there is, so far, little information regarding such exceptional cases. We herein demonstrate a case of non-IgG4-related MFS presenting with periaortitis and parotiditis, whose histological findings were consistent with IgG4-RD despite the absence of elevated serum and tissue IgG4 levels.

To clarify the use of musculoskeletal ultrasonography (US) of ankle joints in rheumatoid arthritis (RA).Consecutive RA patients with or without ankle symptoms participated in the study. The US, clinical examination (CE), and patients' visual analog scale for pain (pVAS) for ankles were assessed. Prevalence of tibiotalar joint synovitis and tenosynovitis were assessed by grayscale (GS) and power Doppler (PD) US using a semi-quantitative grading (0-3). The positive US and CE findings were defined as GS score ≥2 and/or PD score ≥1, and joint swelling and/or tenderness, respectively. Multivariate analysis with the generalized linear mixed model was performed by assigning ankle pVAS as a dependent variable.Among a total of 120 ankles from 60 RA patients, positive ankle US findings were found in 21 (35.0%) patients. The concordance rate of CE and US was moderate (kappa 0.57). Of the 88 CE negative ankles, US detected positive findings in 9 (10.2%) joints. Multivariate analysis revealed that ankle US, clinical disease activity index, and foot Health Assessment Questionnaire, but not CE, was independently associated with ankle pVAS.US examination is useful to illustrate RA ankle involvement, especially for patients who complain ankle pain but lack CE findings.

Objectives: To investigate whether on-demand ultrasonography (US) assessment alongside a routine examination is useful in the management of rheumatoid arthritis (RA). Methods: US was performed in eight (bilateral MCP 2, 3, wrist and knee) joints as the routine in a cumulative total of 406 RA patients. The most symptomatic joint other than the routine joints was additionally scanned. Power Doppler (PD) and gray-scale images were scored semiquantitatively. Eight-joint scores were calculated as the sum of individual scores for the routine joints. Results: The most symptomatic joint was found among the routine joints in 209 patients (Group A) and in other joints in 148 (Group B). The PD scores of the most symptomatic joint correlated well with the 8-joint scores in Group A (rs = 0.66), but not in Group B (rs = 0.33). The sensitivity and specificity of assessment of the most symptomatic joint for routine assessment positivity were high (84.0% and 100%, respectively) in Group A, but low (50.0% and 61.8%, respectively) in Group B. Additional examination detected synovitis in 38% of Group B with negative results in the routine. Conclusions: On-demand US assessment in the most symptomatic joint, combined with the routine assessment, is useful for detecting RA synovitis.

Objectives: To clarify the use of musculoskeletal ultrasonography (US) of ankle joints in rheumatoid arthritis (RA). Methods: Consecutive RA patients with or without ankle symptoms participated in the study. The US, clinical examination (CE), and patients’ visual analog scale for pain (pVAS) for ankles were assessed. Prevalence of tibiotalar joint synovitis and tenosynovitis were assessed by grayscale (GS) and power Doppler (PD) US using a semi-quantitative grading (0–3). The positive US and CE findings were defined as GS score ≥2 and/or PD score ≥1, and joint swelling and/or tenderness, respectively. Multivariate analysis with the generalized linear mixed model was performed by assigning ankle pVAS as a dependent variable. Results: Among a total of 120 ankles from 60 RA patients, positive ankle US findings were found in 21 (35.0%) patients. The concordance rate of CE and US was moderate (kappa 0.57). Of the 88 CE negative ankles, US detected positive findings in 9 (10.2%) joints. Multivariate analysis revealed that ankle US, clinical disease activity index, and foot Health Assessment Questionnaire, but not CE, was independently associated with ankle pVAS. Conclusion: US examination is useful to illustrate RA ankle involvement, especially for patients who complain ankle pain but lack CE findings.

Objectives. To determine whether ultrasonography (US) predicts Boolean remission in rheumatoid arthritis (RA) patients who had achieved disease activity score in 28 joints (DAS28)-based remission criteria. Methods. Thirty-one RA patients in DAS28-based clinical remission were recruited. US semiquantitatively determined Gray scale (GS) and power Doppler (PD) signal scores in the bilateral wrists and all metacarpophalangeals and proximal interphalangeals. Total GS score and total PD score were calculated as the sum of individual scores for each joint. Results. Among 22 RA patients, who maintained DAS28 remission for 2 years, 16 met Boolean remission criteria at the end of study. Both total GS and total PD scores at baseline were significantly lower in Boolean remission group than non-remission group. 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. Among the factors for Boolean remission criteria at 2 years, patient global assessment score was associated with total GS score at the entry, while swollen joint count was related to total PD score. Conclusions. Null or low grade of GS and PD findings in US are associated with achieving Boolean remission. Thus, US is essential for assessment and prediction of “deeper remission” of RA.

Objective. To compare the findings in rheumatoid arthritis (RA)-affected joints between 18F-fluorodeoxyglucose (FDG) and 18F-fluoride (NaF) positron emission tomography (PET)/computed tomography (CT). Methods. We enrolled twelve RA patients who started a new biologic agent (naïve 9 and switch 3). At entry, both hands were examined by 18F-FDG PET/CT, 18F-NaF PET/CT, and X-ray. Intensity of PET signals was determined by standardized uptake value max (SUVmax) in metacarpophalangeal (MCP), proximal interphalangeal (PIP), and ulnar, medial, and radial regions of the wrists. Hand X-rays were evaluated according to the Genant-modified Sharp score at baseline and 6 months. Results. Both 18F-FDG and 18F-NaF accumulated in RA-affected joints. The SUVmax of 18F-FDG correlated with that of 18F-NaF in individual joints (r = 0.65), though detail distribution was different between two tracers. 18F-NaF and 18F-FDG signals were mainly located in the bone and the surrounding soft tissues, respectively. The sum of SUVmax of 18F-NaF correlated with disease activity score in 28 joint (DAS28), modified health assessment questionnaire (MHAQ), and radiographic progression. 18F-FDG and 18F-NaF signals were associated with the presence of erosions, particularly progressive ones. Conclusion. Our data show that both 18F-FDG and 18F-NaF PET signals were associated with RA-affected joints, especially those with ongoing erosive changes.

To determine whether ultrasonography (US) predicts Boolean remission in rheumatoid arthritis (RA) patients who had achieved disease activity score in 28 joints (DAS28)-based remission criteria.Thirty-one RA patients in DAS28-based clinical remission were recruited. US semiquantitatively determined Gray scale (GS) and power Doppler (PD) signal scores in the bilateral wrists and all metacarpophalangeals and proximal interphalangeals. Total GS score and total PD score were calculated as the sum of individual scores for each joint.Among 22 RA patients, who maintained DAS28 remission for 2 years, 16 met Boolean remission criteria at the end of study. Both total GS and total PD scores at baseline were significantly lower in Boolean remission group than non-remission group. 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. Among the factors for Boolean remission criteria at 2 years, patient global assessment score was associated with total GS score at the entry, while swollen joint count was related to total PD score.Null or low grade of GS and PD findings in US are associated with achieving Boolean remission. Thus, US is essential for assessment and prediction of "deeper remission" of RA.

Background Musculoskeletal ultrasonography (US) is one of the standard tools for the diagnosis and monitoring of rheumatoid arthritis (RA). Although we and other groups have proposed several sets of US assessment procedures in arbitrary combinations of selected joints, 1–3 there is still no consensus in defining the joints to evaluate. Objectives To investigate whether US assessment in the selected 8 joints which we advocate as a routine assessment is useful for monitoring response to treatment for RA. Methods Power Doppler (PD) US was performed in 24 joints, including all PIP, MCP, bilateral wrist and knee joints, as comprehensive evaluation in 15 RA patients treated with certolizumab pegol (CZP). Before and after treatment with CZP, PD signals were scored semiquantitatively from 0 to 3 in each joint, and total PD oscore-24 and total PD score-8 were calculated by summing up PD scores of the 24 joints and the selected 8 joints (bilateral second and third MCP, wrist, and knee joints), respectively. 1 Results Amount of change of total PD score-24 by treatment with CZP correlated highly with the changes of disease activity indices, SDAI ( r s =0.91, p r s =0.86, p r s =0.74, p r s =0.86, p r s =0.85, p r s =0.62, p r s =0.42, p >0.05) and evaluator9s global assessment ( r s =0.27, p >0.05). Amount of change of total PD score-8 exhibited stronger correlations with the changes of SDAI ( r s =0.92, p r s =0.89, p r s =0.81, p r s =0.91, p r s =0.39, p >0.05) and evaluator9s global assessment ( r s =0.22, p >0.05) as compared to that of total PD score-24. Conclusions This study suggests that total PD score-8 is useful for monitoring response to treatment in RA patients. References Yoshimi R, Ihata A, Kunishita Y, et al. A novel 8-joint ultrasound score is useful in daily practice for rheumatoid arthritis. Mod Rheumatol 2015; 25:379–85. Backhaus M, Ohrndorf S, Kellner H, et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum 2009;61:1194–201. Naredo E, Rodriguez M, Campos C, et al. Validity, reproducibility, and responsiveness of a twelve-joint simplified power doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis. Arthritis Rheum 2008;59:515–22. Disclosure of Interest None declared

Background Musculoskeletal ultrasonography (US) is one of the standard tools for the diagnosis and monitoring of rheumatoid arthritis (RA). Although we and other groups have proposed several sets of power Doppler (PD) US assessment procedures in arbitrary combinations of selected joints,1-3 they do not always cover all of the affected joints. Objectives To investigate whether US assessment in a selected joint on demand from patients is useful for monitoring RA in daily practice. Methods PDUS was performed in 8 joints (bilateral MCP 2, MCP 3, wrist and knee joints) as the routine in a cumulative total of 406 patients with RA. At the examination, patients declared the most symptomatically affected joint. The declared joint other than the routine 8 joints was additionally scanned. PD signals were scored semiquantitatively from 0 to 3 in each joint, and total PD score-8 was calculated by summing up PD scores of the routine 8 joints.1 Patients with positive PD signals in any joints were regarded as having active synovitis. Results The patients were divided into three groups based on the most affected joints. Group A consisted of 209 patients having the most affected joint among the routine 8 joints, whereas 148 having the most affected joint other than the routine 8 joints were included in Group B. The remaining 49 were asymptomatic at the examination and categorized into Group C. Total PD score-8 was significantly higher in the symptomatic groups (Group A and B) than the asymptomatic group (Group C) (3.66±3.62 vs 1.08±1.56, P Conclusions This study suggests that on-demand US assessment in the most affected joint is practical and helpful for management of RA patients in daily practice. References Yoshimi R, Ihata A, Kunishita Y, et al. A novel 8-joint ultrasound score is useful in daily practice for rheumatoid arthritis. Mod Rheumatol 2014; DOI:10.3109/14397595.2014.974305 (Early online). Backhaus M, Ohrndorf S, Kellner H, et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum 2009;61:1194-201. Naredo E, Rodriguez M, Campos C, et al. Validity, reproducibility, and responsiveness of a twelve-joint simplified power doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis. Arthritis Rheum 2008;59:515-22. Disclosure of Interest None declared

Background Though rheumatoid arthritis (RA) commonly affects feet and ankles, precise clinical evaluation for ankle is difficult because of its complex anatomy and deformity as well as other various factors such as obesity and edema. Objectives To clarify the utility of ultrasonography (US) examination for evaluating RA ankle by means of comparison to physical examination. Methods This study included 56 RA patients (women 82%, age 62±15 y.o., disease duration 7.2±8.2 years, DAS28-ESR 3.95±1.65). Physical examination and patient9s visual analogue scale (VAS) for pain of each bilateral ankle were evaluated. Clinical ankle involvement was defined as ankle joint swelling and/or tenderness on physical examination. Bilateral tibiotalar joints and three tendon sites (anterior tendons; tibialis anterior, extensor hallucis longi, extensor digitorum longi, medial tendons; tibialis posterior, flexor digitorum longi, flexor hallucis longi, lateral tendons; peroneus longi and brevis) were assessed by gray scale (GS) and power Doppler (PD) US examination. Intraarticular synovitis (synovitis) and tenosynovitis were separately assessed by semiquantitative scoring (0-3). Positive US findings were defined as a GS score ≥2 and/or a PD score ≥1. Results Among a total of 112 ankle joints, 28 (25.0%) were clinically swollen and 19 (17.0%) had tenderness. US examination showed that synovitis existed in 17 ankles (19.1%) of all the tibiotalar joints, whereas 23 (20.5%) had tenosynovitis of at least one site among three tendon sites. Tenosynovitis lesions of any tendon in a site were detected at 5 (4.5%) of all the anterior sites, 14 (12.5%) of medial sites, and 13 (11.6%) of lateral sites, respectively. When comparing clinical assessments among 4 groups divided according to the existence of synovitis and tenosynovitis (Table), patient9s VAS of ankle is the highest in the group of ankles affected by both synovitis and tenosynovitis. Positive physical findings (swollen and/or tender) were more highly concordant with tenosynovitis (κ =0.64) than synovitis (κ =0.32), and were also more closely associated with tenosynovitis than in synovitis. When positive US findings were set as the gold standard, sensitivity and specificity of positive physical findings (swollen and/or tender) were 0.56 and 0.81 for synovitis, and 0.73 and 0.87 for tenosynovitis, respectively. Conclusions This study shows that physical examinations of the ankles often reflect tenosynovitis rather than intraarticular synovitis. US sensitively illustrate RA involvement in the ankle joints, particularly intraarticular lesions, which are often overlooked by physical examination. Disclosure of Interest None declared

Background In the update of EULAR recommendations for management of rheumatoid arthritis (RA) in 2013, both TNF inhibitor (TNFi) and non-TNFi biologics (BIOs) are listed as a first biologics. A number of studies have shown that the therapeutic response to a BIOs is unfavorable in patients who failed to respond to previous BIOs compared with BIO-naive patients. Little data are available to compare the response of tocilizumab (TCZ) as the first BIO with that as the second BIO, because TCZ had been recognized as the second line BIO until the 2013 EULAR recommendations. Objectives To compare clinical responses of TCZ between BIO-naive patients and non-responders to the first TNFi in RA. Methods Patients with RA, who were registered in Y-CURD, the integrated database of patients at our department and its affiliated hospitals, and treated with TCZ as the first BIO (BIO-naive group) and the second BIO after TNFi (infliximab, etanercept and adalimumab) failure (TNFi failure group) along with methotrexate were included in the study. We compared the clinical efficacy of TCZ as the first and second BIO by assessing tender joint count (TJC), swollen joint count (SJC), patient global assessment (PGA), and DAS28-ESR at 12 months after starting TCZ. Results Among 40 patients recruited, 18 and 22 belonged to the BIO-naive and TNFi failure groups, respectively. There was no significant difference in patient demographics including age (50.1±3.5 vs 52.2±3.6 yr), disease duration (9.1±3.5 vs 8.1±3.3 yr), and ACPA positivity (71.4% vs 81.8%) and all baseline clinical parameters, including TJC (7.7±1.3 vs 7.7±1.3), SJC (7.2±1.3 vs 6.0±1.1), PGA (50.2±5.4 vs 60.1±5.1 mm), and DAS28-ESR (5.45±0.31 vs 5.75±0.29), between the two groups. Although all these parameters were significantly reduced during the first 3 months after starting TCZ in the both groups, the levels of PGA and DAS28-ESR were significantly lower in the BIO-naive group than the TNFi failure group (13.4±4.3 vs 31.0±6.6 mm, respectively, p =0.045, and 2.06±0.46 vs 3.20±0.30, respectively, p =0.041). Clinical remission rate based on DAS28-ESR was significantly higher in BIO-naive group than in the TNFi failure group at 3 months (72.7% vs 26.7%, p =0.045), while there was no significant difference in remission rate from 6 to 12 months after starting TCZ between the two groups. Conclusions Our data showed that TCZ acted more immediately in BIO-naive RA patients as compared to non-responder to TNFi, whereas the long-term effectiveness of TCZ was equivalent between the two groups. TCZ may have a unique feature characterized by the efficacy irrelevant to the history of TNFi use. Disclosure of Interest None declared

Background Both TNF inhibitor (TNFi) and non-TNFi biologics can be the first biologics for patients with rheumatoid arthritis (RA) in 2013 EULAR recommendations, whereas definitive therapeutic algorithm is not shown in RA patients who failed to respond to a particular biologics as the first line. In non-responders to the first TNFi, superiority of non-TNFi biologics to alternative TNFi as the second choice is suggested by the high drug retention rate. Objectives To compare clinical responses of tocilizumab with that of TNFi as the second biologics in RA patients after treatment failure with a TNFi as the first choice. Methods Patients with RA who were registered in Y-CURD, the integrated database of patients at our department and its affiliated hospitals, and have been treated with TNFi (infliximab, etanercept, adalimumab) as the first biologics followed by another biologics. They were divided into two groups, TT group (TNFi – TNFi) and T6 gourp (TNFi – tocilizumab). We compared the clinical efficacy of the second biologics by assessing DAS28-ESR and the individual components between the two groups for 12 months after switching biologics. Results Among 86 patients recruited, 57 and 29 belonged to TT and T6 groups, respectively. There was no significant difference in the reasons for switching biologics (p=0.41): in TT group, primary non-response in 18, secondary non-response in 37, and other reasons in 2, while in T6 group, primary non-response in 6, secondary non-response in 22, and adverse effect in 1. There was no significant difference in other baseline parameters, including TJC, SJC, PGA, and DAS28-ESR, between the two groups. DAS28-ESR was significantly reduced during the first 3 months after switching in both groups, though the reduction was larger in T6 group than TT group (2.72±1.14 vs 1.43±1.55, p=0.0005). Further sustained reduction of DAS28-ESR was found in T6 group, but not TT, from 3 to 12 months after switching. Of the individual components of DAS28, tender joint count and patient global assessment were significant decreased in T6 group compared to TT group at 12 months (0.38±0.62 vs 2.54±4.11, p=0.027, and 14.3±17.3 vs 28.1±24.0, p=0.031, respectively). Conclusions Our data showed that tocilizumab was more effective as the second biologic than alternative TNFi in RA patients who had previously treated with a TNFi as the first biologics. As tocilizumab might be an appropriate biologic as the first choice in such cases, further analyses as to the clinical characteristics of more accumulated cases can provide clues to optimized selection of biologics. References Du Pan SM et al. Differential drug retention between anti-TNF agents and alternative biological agents after inadequate response to an anti-TNF agent in rheumatoid arthritis patients. Ann Rheum Dis 2012;71:997-9. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5168

Although the increased expression of type I interferon (IFN)-inducible genes, called “IFN signature”, has been suggested to have important roles in pathogenesis of systemic lupus erythematosus (SLE), its mechanism still remains unclear. Recent studies in vitro or with mice suggest that TRIM21, an autoantigen also called Ro52 or SSA1, is involved in the regulation of type I IFN production as an E3 ubiquitin ligase for IFN regulatory factors (IRFs). Here, we investigated the pathological role of TRIM21 in SLE. We collected peripheral blood mononuclear cells (PBMCs) from 20 patients with SLE and 24 healthy controls (HC). The mRNA levels of TRIM21 and other type I IFN-inducible genes were higher in PBMCs from patients with SLE as compared to HC. Thus, TRIM21 mRNA levels correlated positively with other type I IFN-inducible genes. On the other hand, type I IFN mRNA levels showed a negative correlation with TRIM21 mRNA levels in HC but not in patients with SLE. Consistent with higher TRIM21 mRNA levels, TRIM21 protein levels were higher in SLE patients as compared to HC. After treating with MG-132, the protein levels of IRFs were increased in PBMC from HC, but not in the PBMC from patients with SLE. These results suggest that dysregulation of TRIM21 to function as an E3 ubiquitin ligase for IRF family may be associated with the increased expression of type I IFNs in SLE.