Reikou Kamiyama

A novel 8-joint ultrasound score is useful in daily practice for rheumatoid arthritis

Abstract Objectives. To investigate the optimal number and combination of joints to be assessed by power Doppler ultrasonography (PDUS) in daily practice for rheumatoid arthritis (RA). Methods. 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. Results. 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, p < 0.01). Conclusions. Total PD score-8 is simple and efficient enough for monitoring disease activity and judging imaging remission of RA in daily practice.

(18)F-FDG and (18)F-NaF PET/CT demonstrate coupling of inflammation and accelerated bone turnover in rheumatoid arthritis.

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.

Ultrasonography predicts achievement of Boolean remission after DAS28-based clinical remission of rheumatoid arthritis

Abstract 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.

Successful treatment of a patient with refractory haemophagocytic syndrome in systemic lupus erythematosus with mycophenolate mofetil

Abstract 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.

Musculoskeletal ultrasonography delineates ankle symptoms in rheumatoid arthritis

Abstract 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.

Dysfunction of TRIM21 in interferon signature of systemic lupus erythematosus

Abstract Objectives: 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). Methods: 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. Results: 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. Conclusion: 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.

On-demand ultrasonography assessment in the most symptomatic joint supports the 8-joint score system for management of rheumatoid arthritis patients

Abstract 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.

FRI0419 The predictive prognostic factors for clinical course of polymyositis/dermatomyositis-associated interstitial lung disease

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 PaCO2 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 PaCO2 (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

AB0416 Which factors predict the responsiveness to tocilizumab in rheumatoid arthritis? the difference between the usage as the first biologic and as the second biologic

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

AB0973 The 8-Joint Ultrasound Score Is Useful for Monitoring Response To Treatment for Rheumatoid Arthritis

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 (rs =0.91, p <0.01) and DAS28-CRP (rs =0.86, p <0.01). Although it correlated well with the changes of some components of disease activity indices, including swollen joint count (rs =0.74, p <0.01), tender joint count (rs =0.86, p <0.01), CRP (rs =0.85, p <0.01) and ESR (rs =0.62, p <0.01), there were no significant correlations between the changes of total PD score-24 and the changes of patients global assessment (rs =0.42, p >0.05) and evaluators global assessment (rs =0.27, p >0.05). Amount of change of total PD score-8 exhibited stronger correlations with the changes of SDAI (rs =0.92, p <0.01) and DAS28-CRP (rs =0.89, p <0.01) as compared to that of total PD score-24 (Figure 1). The change of total PD score-8 correlated more highly with the changes of swollen joint count (rs =0.81, p <0.01) and tender joint count (rs =0.91, p <0.01), while it showed lower correlation coefficients with the changes of patients global assessment (rs =0.39, p >0.05) and evaluators global assessment (rs =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