Kaoru Takase

Successful switching to adalimumab in an infliximab-allergic patient with severe Behçet disease-related uveitis.

Infliximab has demonstrated remarkable effects on controlling uveitis in patients with Behçet’s disease (BD). However, there is no way except for discontinuation of infliximab treatment in patients who are intolerant to the agent due to hypersensitivity reactions. We here report successful switching from infliximab to adalimumab in a BD patient. Treatment with infliximab had maintained clinical remission in the patient having refractory ocular lesions to cyclosporine until the patient had experienced repeated infliximab-related infusion reactions. Discontinuation of the therapy led to another ocular attacks immediately. Switching to adalimumab induced clinical remission again. Our experience suggest adalimumab is a safe and effective option for patients having hypersensitivity to infliximab.

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.

Reactivation of hepatitis B virus in a hepatitis B surface antigen-negative patient with rheumatoid arthritis treated with methotrexate

Immunosuppressive therapy can induce viral reactivation in patients with chronic hepatitis B virus (HBV) infection and, more rarely, in patients with resolved HBV infection. We report the case of a 57-year-old Japanese woman with rheumatoid arthritis (RA) who developed de-novo hepatitis B virus-related hepatitis after methotrexate (MTX) therapy. Entecavir and oral prednisolone following steroid pulse therapy were administered and her liver function recovered. MTX is widely used for RA for its efficiency and safety. But some cases of HBV reactivation caused by MTX, including de-novo hepatitis, have been reported. Considering these conditions, more attention should be paid when using MTX in patients with RA. And more studies are needed to determine who needs screening of HBV, monitoring of HBV-DNA, and prophylaxis with chemotherapy or immunosuppressive therapy.

Bach1 regulates osteoclastogenesis in a mouse model via both heme oxygenase 1–dependent and heme oxygenase 1–independent pathways

OBJECTIVE Reducing inflammation and osteoclastogenesis by heme oxygenase 1 (HO-1) induction could be beneficial in the treatment of rheumatoid arthritis (RA). However, the function of HO-1 in bone metabolism remains unclear. This study was undertaken to clarify the effects of HO-1 and its repressor Bach1 in osteoclastogenesis. METHODS In vitro osteoclastogenesis was compared in Bach1-deficient and wild-type mice. Osteoclasts (OCs) were generated from bone marrow-derived macrophages by stimulation with macrophage colony-stimulating factor and RANKL. Osteoclastogenesis was assessed by tartrate-resistant acid phosphatase staining and expression of OC-related genes. Intracellular signal pathways in OC precursors were also assessed. HO-1 short hairpin RNA (shRNA) was transduced into Bach1(-/-) mouse bone marrow-derived macrophages to examine the role of HO-1 in osteoclastogenesis. In vivo inflammatory bone loss was evaluated by local injection of tumor necrosis factor α (TNFα) into calvaria. RESULTS Transcription of HO-1 was down-regulated by stimulation with RANKL in the early stage of OC differentiation. Bach1(-/-) mouse bone marrow-derived macrophages were partially resistant to the RANKL-dependent HO-1 reduction and showed impaired osteoclastogenesis, which was associated with reduced expression of RANK and components of the downstream TNF receptor-associated factor 6/c-Fos/NF-ATc1 pathway as well as reduced expression of Blimp1. Treatment with HO-1 shRNA increased the number of OCs and expression of OC-related genes except for the Blimp1 gene during in vitro osteoclastogenesis from Bach1(-/-) mouse bone marrow-derived macrophages. TNFα-induced bone destruction was reduced in Bach1(-/-) mice in vivo. CONCLUSION The present findings demonstrate that Bach1 regulates osteoclastogenesis under inflammatory conditions, via both HO-1-dependent and HO-1-independent mechanisms. Bach1 may be worthy of consideration as a target for treatment of inflammatory bone loss in diseases including RA.

Use of musculoskeletal ultrasound in Japan: a survey of practicing rheumatologists

We aimed to describe how often Japanese rheumatologists currently use musculoskeletal ultrasound (MSUS), and how they are currently being trained in the use of this imaging technique. Questionnaires were sent to 200 Japanese rheumatologists: 100 to participants attending the first Scientific Meeting of the Japanese Society of Imaging in Rheumatic Diseases in 2006, and 100 to other randomly selected rheumatologists certified by the Japan College of Rheumatology. A total of 139 questionnaires (74 from meeting participants, 65 from randomly selected rheumatologists) were completed and analyzed. Twenty-four of the 74 respondents (32.4%) in the meeting participants group used MSUS imaging for patient management, while only 7 of the 65 respondents (10.8%) in the certified rheumatologists group used MSUS imaging for patient management. Sixty-five of the 74 respondents (87.8%) in the meeting participants group and 54 of the 65 respondents (83.1%) in the certified rheumatologists group considered MSUS to be a useful tool. Only a minority of respondents used MSUS in the management of their patients. Lack of training in MSUS was the principal reason for not performing MSUS. Japanese rheumatologists would prefer future training in the form of intensive courses and training sessions.

Multiple extra-articular synovial cysts complicated with rheumatoid arthritis.

Multiple extra-articular synovial cysts (MESC) are rarely complicated with various rheumatic diseases. We here first report a rheumatoid arthritis (RA) patient with MESC, which were extensively analyzed by a series of imaging techniques including fluorine-18-2-fluoro-d-glucose positron emission tomography (18F-FDG-PET), magnetic resonance imaging (MRI), and ultrasonography. FDG uptakes in joint lesions with MESC were much higher than those reported in typical lesions of RA, suggesting that marked joint inflammation is implicated in the development of MESC.

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