Search

In recent years, advances in pharmacotherapy for rheumatoid arthritis (RA) have dramatically improved the control of disease activity. However, a significant number of patients still develop forefoot deformity. The purpose of this study was to investigate the results of more than 20 years' follow-up of metatarsal neck shortening oblique osteotomy (SOO) for forefoot deformity in patients with RA.The metatarsal neck SOO was performed on 163 feet in 108 patients between January 1985 and December 1996 in the authors' hospital. For the patients, who met the survey criteria, an observational study was performed clinically and radiologically at the baseline and at more than 20 years after surgery.A retrospective cohort study was conducted on 36 feet in 22 patients, all of whom were female, and the mean age at surgery was 45.6 (35.0-63.0) years old. The follow-up period was 25.1 (21.0-31.0) years. The presence of painful callosities in the surgically treated feet without revised surgeries decreased from 32 feet (100%) to 4 feet (12.5%) at the last follow-up with mild pain that did not cause any footwear problems. Re-osteotomy at the metatarsal of the lessor toe was performed on four feet in two patients. Radiologically, among 128 toes without revised surgeries, 85% were able to have the joint space preserved, and 89% maintained a pain-free condition without any recurrence of deformity. The mean total Japanese Society for Surgery for the Foot (JSSF) RA foot and ankle score was 64.0/100, and the visual analogue scale (VAS) of overall satisfaction was 62 (0: dissatisfied, 100: highly satisfied). The overall satisfaction had a positive correlation with calcaneal pitch and negative correlation with joint space narrowing at the talocrural joint.Metatarsal neck SOO appeared to be effective for patients with RA. The deformity was corrected and retained for a long time.

Objective Treatment of elderly patients with rheumatoid arthritis (RA) has been controversial because they often have serious comorbidities and cannot use methotrexate (MTX). In Japan, golimumab (GLM) 100 mg without MTX is approved. We investigated the effectiveness and safety of GLM in elderly patients with RA. Methods The GLM survival rate was evaluated using the Kaplan-Meier method. Disease activities, laboratory findings, and treatments were evaluated. Patients We enrolled 168 patients with RA in our hospital. Using age ≥75 years old to identify elderly patients, younger (n=111) and elderly (n=57) groups were established. Elderly patients were divided into 2 groups according to the MTX treatment status (with, n=27; without, n=25). Results The GLM survival rates were 80.8% and 82.3% in elderly and younger patients, respectively (p=0.762). At 52 weeks, the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) was improved in elderly patients (4.26 vs. 3.31, p0.001); the Health Assessment Questionnaire Disability Index (HAQ-DI) was unchanged (1.12 vs. 0.88, p=0.694). When elderly patients were compared according to the MTX treatment status, the DAS28-ESR had improved in both groups (with MTX: 3.82 vs. 2.68, p0.001; without MTX: 4.76 vs. 4.25, p=0.026); however, the HAQ-DI had not. The GLM survival rates at 52 weeks were 85% and 76% in patients with and without MTX, respectively. Conclusion In elderly patients with RA, GLM was effective, regardless of MTX treatment status, but it did not affect the HAQ-DI. GLM survival rates were comparable between elderly and younger patients. GLM may be a suitable option for elderly patients with RA who cannot use MTX.

Objectives To investigate the outcomes of the modified Thompson–Littler (m-TL) method, a corrective surgical method utilising a dynamic tenodesis, in patients with rheumatoid swan-neck deformity. Methods Twenty-seven fingers in 10 patients with rheumatoid arthritis (RA) underwent surgical correction. The mean age at the time of surgery was 60.3 (45–77) years, the mean duration of RA was 19.3 (4–34) years, and the mean postoperative follow-up period was 2.4 (0.5–6) years. Results The deformity was corrected and the proximal interphalangeal (PIP) joint pain disappeared in all operated fingers. The mean pinch power between the thumb and the operated finger increased. The active extension decreased, the active flexion increased, and the total arc of motion decreased. Comparing the range of motion by Nalebuff’s type classification, the postoperative arc of motion decreased as the type advanced. Conclusions The m-TL method provided a favourable outcome in cases of Type ≤III rheumatoid swan-neck deformity without severe joint deterioration at the PIP joint. Aesthetic and functional improvements were observed and the patients were satisfied with the operation.

Objective To evaluate the effectiveness and drug retention rate of golimumab (GLM) for long-term use in daily practice for patients with rheumatoid arthritis (RA). Methods Patients with RA who started GLM therapy with a minimum follow-up period of 52 weeks were included. The patients were divided into a biologic-naive group and switch group. The disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) (DAS28-ESR), grip power, and Japanese version of the health assessment questionnaire (J-HAQ) score were assessed. In addition, the treatment continuation rate was evaluated at the final follow-up. Patients Sixty-five patients (58 women and 7 men; median [range] age, 69 [61-74] years; median [range] disease duration, 9 [5-16] years) were included. Twenty-eight patients were biologic-naive (naive group), and 37 were switched to biologics (switch group). Results The median (range) follow-up period was 134 (58-162) weeks. The DAS28-ESR improved from a median (range) of 4.31 (3.52-5.25) to 2.65 (2.28-3.77) in the naive group and from 4.27 (3.19-4.89) to 2.89 (2.49-3.88) in the switch group. The grip power improved in both groups (p

Objectives The incidence of femoral localized periosteal thickening (LPT), which can precede atypical femoral fracture (AFF), is not low (1–10%) in Japanese patients with autoimmune inflammatory rheumatic diseases (AIRDs). We explored the associations between underlying AIRDs and the prevalence of LPT. Methods We conducted post hoc analyses of two cohorts that included a total of 280 Japanese women, 105 of whom had AIRDs and had been taking bisphosphonate (BP) and prednisolone (PSL) and 175 of whom had rheumatoid arthritis (RA). Results LPT was detected in a total of 18 patients (6.4%) and 3 (1.1%) developed AFFs. RA was negatively correlated with LPT. A disease other than RA requiring glucocorticoid treatment, BP use ≥5 years, PSL use ≥7 years, and a PSL dose ≥5.5 mg/day were positively correlated with LPT. After adjusting for age, diabetes mellitus, and BP duration or daily PSL dose, RA was no longer associated with LPT. Conclusions LPT in Japanese patients with AIRDs was associated with BP and glucocorticoid treatment rather than underlying AIRDs. When PSL dose ≥5.5 mg/day is required long-term [typically combined with long-term BP treatment (≥5 years)], clinicians need to pay particular attention in cases LPT and AFF as well as glucocorticoid-induced osteoporosis.

Hepcidin, a major regulator of iron metabolism and homeostasis, is regulated by inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis, and the aim of this study was to determine whether serum hepcidin levels are correlated with the degree of osteoporosis in patients with rheumatoid arthritis (RA). A total of 262 patients with RA (67.5 ± 11.4 years; 77.5% female) were enrolled. Serum iron, ferritin, and hepcidin levels were positively correlated each other. Multiple regression analyses revealed that the serum iron level was positively correlated with femoral T and Z scores, whereas the serum hepcidin level was not. Serum hepcidin level was correlated with the serum 25-hydroxy vitamin D level, which was in turn positively related to the femoral Z score. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in patients with RA.

Objective To evaluate the effectiveness and drug retention rate of golimumab (GLM) for long-term use in daily practice for patients with rheumatoid arthritis (RA). Methods Patients with RA who started GLM therapy with a minimum follow-up period of 52 weeks were included. The patients were divided into a biologic-naïve group and switch group. The disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) (DAS28-ESR), grip power, and Japanese version of the health assessment questionnaire (J-HAQ) score were assessed. In addition, the treatment continuation rate was evaluated at the final follow-up. Patients Sixty-five patients [58 women and 7 men; median (range) age, 69 (61-74) years; median (range) disease duration, 9 (5-16) years] were included. Twenty-eight patients were biologic-naïve (naïve group), and 37 were switched to biologics (switch group). Results The median (range) follow-up period was 134 (58-162) weeks. The DAS28-ESR improved from a median (range) of 4.31 (3.52-5.25) to 2.65 (2.28-3.77) in the naïve group and from 4.27 (3.19-4.89) to 2.89 (2.49-3.88) in the switch group. The grip power improved in both groups (p

Objective To investigate the clinical outcomes of rheumatoid arthritis (RA) patients who discontinued infliximab (IFX) treatment at our hospital. Methods Among 249 patients receiving IFX from 2007 to 2015, we retrospectively investigated the clinical courses of 18 who discontinued IFX after achieving the 28-joint disease activity score based on the erythrocyte sedimentation (DAS28-ESR) clinical remission (CR) and whose clinical courses were available continuously for 96 weeks after discontinuation. Results At IFX introduction, the median age was 56.9 (range 36.1-72.4) years, and the disease duration was 5.2 (0.4-25.6) years. The median duration of maintaining either CR or a low disease activity (LDA) with IFX was 37.2 (4.0-91.4) months, and the total duration of IFX therapy was 45.8 (17.1-96.9) months. After discontinuation, 8 patients (44.4%) maintained CR/LDA for 96 weeks (no-flare group), and 10 (55.6%) experienced flares (DAS28-ESR≥3.2) within 96 weeks (flare group). In the no-flare group, six patients receiving intensified conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy to prevent flare ups simultaneously either with or immediately after discontinuing IFX. In the flare group, four patients received intensified csDMARD therapy. Six patients restarted biological DMARDs (bDMARDs), and all achieved CR again. Ultimately, 12 patients (66.7%) maintained a Bio-free disease control for 96 weeks. A comparison of the clinical backgrounds between the flare and no-flare groups showed no marked difference in their disease duration, IFX dosage, duration of maintaining CR with IFX, or concomitant csDMARDs use. Conclusion Irrespective of the RA disease duration, more than half of all patients maintained a Bio-free condition for 96 weeks. Continuing LDA with IFX for a sufficiently long period of time before discontinuation and preventive intensification of csDMARD therapy may help maintain a Bio-free condition.

Objective To investigate the clinical outcomes of rheumatoid arthritis (RA) patients who discontinued infliximab (IFX) treatment at our hospital. Methods Among 249 patients receiving IFX from 2007 to 2015, we retrospectively investigated the clinical courses of 18 who discontinued IFX after achieving the 28-joint disease activity score based on the erythrocyte sedimentation (DAS28-ESR) clinical remission (CR) and whose clinical courses were available continuously for 96 weeks after discontinuation. Results At IFX introduction, the median age was 56.9 (range 36.1-72.4) years, and the disease duration was 5.2 (0.4-25.6) years. The median duration of maintaining either CR or a low disease activity (LDA) with IFX was 37.2 (4.0-91.4) months, and the total duration of IFX therapy was 45.8 (17.1-96.9) months. After discontinuation, 8 patients (44.4%) maintained CR/LDA for 96 weeks (no-flare group), and 10 (55.6%) experienced flares (DAS28-ESR≥3.2) within 96 weeks (flare group). In the no-flare group, six patients receiving intensified conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy to prevent flare ups simultaneously either with or immediately after discontinuing IFX. In the flare group, four patients received intensified csDMARD therapy. Six patients restarted biological DMARDs (bDMARDs), and all achieved CR again. Ultimately, 12 patients (66.7%) maintained a Bio-free disease control for 96 weeks. A comparison of the clinical backgrounds between the flare and no-flare groups showed no marked difference in their disease duration, IFX dosage, duration of maintaining CR with IFX, or concomitant csDMARDs use. Conclusion Irrespective of the RA disease duration, more than half of all patients maintained a Bio-free condition for 96 weeks. Continuing LDA with IFX for a sufficiently long period of time before discontinuation and preventive intensification of csDMARD therapy may help maintain a Bio-free condition.

The present study aims to evaluate changes in plantar pressure distribution after joint-preserving surgery for rheumatoid forefoot deformity. A retrospective study was performed on 26 feet of 23 patients with rheumatoid arthritis (RA) who underwent the following surgical combination: modified Mitchell’s osteotomy (mMO) of the first metatarsal and shortening oblique osteotomy of the lateral four metatarsals. Plantar pressure distribution and clinical background parameters were evaluated preoperatively and one year postoperatively. A comparison of preoperative and postoperative values indicated a significant improvement in the visual analog scale, Japanese Society for Surgery of the Foot scale, and radiographic parameters, such as the hallux valgus angle. A significant increase in peak pressure was observed at the first metatarsophalangeal joint (MTPJ) (0.045 vs. 0.082 kg/cm2, p &lt, 0.05) and a significant decrease at the second and third MTPJs (0.081 vs. 0.048 kg/cm2, 0.05, 0.097 vs. 0.054 kg/cm2, 0.05). While overloading at the lateral metatarsal heads following mMO has been reported in previous studies, no increase in peak pressure at the lateral MTPJs was observed in our study. The results of our study show that this surgical combination can be an effective and beneficial surgical combination for RA patients with mild to moderate joint deformity.

Background In the treatment of Rheumatoid arthritis (RA), early diagnosis and early treatment with tight control have become increasingly important with the advent of biological therapy. Ultrasonography (US) of the various joints enables the real-time evaluation of synovial hypertrophy, effusion and bone erosion, Power Doppler (PD) ultrasound is able to identify both subclinical synovitis and early erosive disease. Objectives The objectives of this study were to investigate whether the image of US at the operated joint reflect synovium histological findings or clinical indicators, and to compare the results in the patient treated by non-biological agent (NonBio) and biological agent (Bio) Methods RA related orthopaedic surgery was performed at 1287 joints including 17 shoulders, 160 knees, 96 elbows, 378 wrists, 364 fingers, 38 ankles and 234 toes during the period between January 2011 and December 2018 at our rheumatic center. Preoperatively, ultrasound evaluations were performed and grade of PD signal was determined at the part with the highest signal. PD signal consists 4 grades from grade 0 to 3. The operations were performed within one week after the ultrasound evaluations. Rooney score of the synovium histology, DAS28-ESR(4), MMP-3, CRP were investigated. Rooney score represents the histologic features in the synovium of RA. It includes 6 features i.e. synoviocytes hyperplasia, fibrosis, proliferating blood vessels, perivascular infiltrates of lymphocytes, focal aggregates of lymphocytes, diffuse infiltrates of lymphocytes. They were scored separately on a scale of 1-10.The treatments that the patients received included: biological agents (Bio) (n=389 30%), etanercept (ETN) (n= 102), tocilizumab (TCZ) (n=105), infliximab (IFX) (n=29), adalimumab (ADA) (n=28), certlizumab pegol (CZP) (n=12), golimumab (GLM) (n=56), and abatacept (ABT) (n=55), tofacitinib (TOF) (n=2). Results PD signal (0.97±0.88), DAS28 (3.23±1.13), CRP(0.5±1.25 mg/dL), MMP-3 (119.0±119.0 ng/mL) and Rooney score (23.5±7.7) in the patients treated with Bio were significantly lower than those (1.39±0.95, 3.66±1.07, 0.78±1.37 mg/dL, 146.3±150.0ng/dL, 28.5±9.26) in the patients treated with NonBio. Rooney score fibrosis (9.57±1.44) in patients treated with Bio was significantly higher than those (8.64±2.48) in patients treated by NonBio. Rooney score, synoviocyte hyperplasia (1.16±1.26) and three items of lymphocyte (1.59±2.91, 1.68±2.54, 1.11±2.20) in patients treated with Bio were lower than those (1.72±1.30, 3.79±3.56, 3.73±3.53, 2.40±2.98) in patients treated with NonBio. TCZ, ADA, ABT and IFX had some significant differences for Rooney score and Rooney item score between the patients treated with NonBio. Conclusion The activity of RA synovitis at operated site was suppressed in patients treated with Bio. There were some differences in clinical data, histological score, PD signal and DAS28 among Bio. Disclosure of Interests None declared

Background Sarcopenia is characterized by a loss of muscle mass and strength, which leads to a reduced physical ability, poor quality of life (QoL), frailty and mortality. Rheumatoid arthritis (RA) is considered a cause of secondary sarcopenia. Objectives To clarify the effectiveness of biologic disease-modifying anti-rheumatic drugs (bDMARDs) on sarcopenia, including the physical ability, body composition and nutritional status. Methods This was a prospective cohort study including consecutive 41 patients (11 men, 30 women, 63.6±16.1 years old) with RA who started bDMARDs for the first time at Niigata Rheumatic Center. The diagnosis of secondary sarcopenia was made according to the diagnostic algorithm of the Asian Working Group for Sarcopenia (AWGS), excluding the criteria about older age. We observed the disease activity of RA, physical ability, body composition, nutritional status and QoL at baseline and 6 months. The disease activity was assessed by the disease activity score-28 joint count erythrocyte sedimentation rate (DAS28-ESR) and clinical disease activity index (CDAI). The physical activity was determined using the health assessment questionnaire (HAQ), 10-m walking test (10MWT) and timed up and go test (TUG). The nutritional status was determined based on the controlling nutrition status (CONUT) score and prognostic nutritional index (PNI). The overall QoL was measured by European quality of life scale- 5 dimensions (EQ-5D). Results Among 41 patients who started bDMARDs, 19 were classified as having sarcopenia, and 7 were classified as having pre-sarcopenia. The bDMARD was certolizumab pegol in 10 patients, adalimumab in 7, abatacept in 7, golimumab in 6, tocilizumab in 5, infliximab in 3 and etanercept in 3. The DAS28-ESR (4.7±1.3 vs. 2.6±1.3, p Conclusion After 6 months of bDMARDs therapy, the physical ability, nutritional status and QoL were significantly ameliorated. While the muscle mass was not markedly increased, the proportion of patients with sarcopenia showed a decreasing trend. The administration of bDMARDs might be useful for preventing secondary sarcopenia in RA patients. Disclosure of Interests Eriko Hasegawa: None declared, Satoshi Ito Speakers bureau: Mitsubishi Tanabe Pharma Corporation., Yoichi Kurosawa: None declared, Daisuke Kobayashi: None declared, Asami Abe: None declared, Hiroshi Otani: None declared, Kiyoshi Nakazono: None declared, Akira Murasawa: None declared, Ichiei Narita: None declared, Hajime Ishikawa: None declared

Background The treatment aim of rheumatoid arthritis (RA) is achieving and maintaining functional remission via tight medical control. However, if adequate medication is not administered in the very early stage of the disease, surgical reconstruction for the structurally damaged hand and wrist is sometimes required. Objectives To evaluate the effect of surgical treatment of the hand and wrist(1) and to set the target of functional remission using grip power and patient-reported outcome measures (PROs) at baseline. Methods A prospective observational cohort study was performed in RA patients who were scheduled to have primary hand and/or wrist surgeries. Assessments were performed at baseline and 12 months after surgery using grip power (GP), pain visual analogue scale (pain VAS), general health (GH), disease activity score 28- C-reactive protein(4) (DAS28-CRP(4)), disabilities of the arm, shoulder and hand (DASH), European quality of life scale with five dimensions (EQ-5D), Beck depression inventory -II (BDI-II) and health assessment questionnaire- disability index (HAQ-DI) for all registered patients. Baseline data for each item in the group with HAQ remission (HAQ-DI≤0.5) at 12 months (REM) were compared with those in the group without remission at 12 months (non-REM). Results There were 137 sites (63 hands, 74 wrists) in 119 patients whose average age was 62 (19-88) years and average disease duration was 14 (1-45) years. Overall, the physical function (GP, pain VAS, DASH, HAQ-DI), quality of life (HAQ-DI, GH, EQ-5D), depression (BDI-II) and disease activity (DAS28-CRP(4)) had significantly improved at 12 months (p Conclusion GP and other four PROs were validated as good objective tools for assessing the physical function after hand and wrist surgeries. It would be helpful for rheumatologists to consider the timing of surgery in RA patients based on the cut-offs determined in this study(2). References [1] Ishikawa H. The latest treatment strategy for the rheumatoid hand deformity. J Orthop Sci. 2017; 22: 583-592. [2] Kojima T, Ishikawa H, Tanaka S, et al. Target setting for lower limb joint surgery using the timed up and go test in patients with rheumatoid arthritis: A prospective cohort study. Int J Rheum Dis. 2018; 21: 1801-1808. In the other items, there was not a significant difference between two groups Disclosure of Interests Hajime Ishikawa: None declared, Asami Abe: None declared, Toshihisa Kojima: None declared, Masayo Kojima: None declared, Yoichi Kurosawa: None declared, Eriko Hasegawa: None declared, Satoshi Ito Speakers bureau: Mitsubishi Tanabe Pharma Corporation., Naoki Ishiguro: None declared, Akira Murasawa: None declared

Objective Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by periarticular and systemic osteoporosis. Fibroblast growth factor 23 (FGF23), which is mainly produced by osteocytes, circulates to the kidneys and regulates bone metabolism. We herein assessed serum FGF23 and its relationship to inflammation and osteoporosis in patients with RA. Methods Sixty-one patients with RA were included. Serum concentrations of FGF23 were determined using a sandwich enzyme-linked immunosorbent assay. Results The mean (± standard deviation) serum FGF23 concentration was 34.9±9.2 (range, 21.0-61.0) pg/mL. The serum FGF23 level was significantly and positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, disease activity score-28 based on the ESR (DAS-28 ESR) and DAS-28 CRP (r=0.261, p=0.044, r=0.280, p=0.029, r=0.409, p=0.001 and r=0.421, p=0.001, respectively). The serum matrix metalloproteinase-3 level was also significantly and positively correlated with the serum FGF23 level (r=0.331, p=0.015). Concentrations of type I collagen cross-linked N-telopeptide in the serum was significantly correlated with the serum FGF23 level (r=0.272, p=0.034). Neither the bone mineral density in the femoral neck nor lumbar was significantly correlated with the serum FGF23 level. Serum phosphate, calcium, 25-hydroxy vitamin D, and intact parathyroid hormone were not related to the serum FGF23 level. Conclusion In patients with RA, serum FGF23 is correlated with inflammation, the disease activity of RA, and bone absorption markers. Serum FGF23 may be associated with abnormal bone absorption related to RA inflammation. Further studies are necessary to clarify the mechanism underlying this association.

Background:It has been suggested that perioperative use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in rheumatoid arthritis (RA) patients carries risks for the surgical-site infection and the delayed wound healing (DWH); however, the risk of DWH with perioperative use of bDMARDs has not reached a general consensus.Objectives:This retrospective study aimed to investigate the risk factors associated with DWH after orthopedic surgery in RA patients treated with bDMARDs.Methods:We reviewed medical records of 277 orthopedic procedures for 188 RA patients treated with bDMARDs between from 2014 to 2017 in Niigata Rheumatic Center. As preoperative nutritional status assessment, we evaluated body mass index (BMI), prognostic nutritional index (PNI), and CONtrolling NUTritional status (CONUT). In addition, we evaluated DAS28-CRP, DAS28-ESR, face scale for pain, global health (GH), and Health Assessment Questionnaire-Disability Index (HAQ-DI) to assess the disease activity. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factor for DWH.Results:The major characteristics of the patients in 277 procedures were mean age of 63.2 years old and mean disease duration of 18.2 years. Surgical site were hand and wrist (145 procedures), foot and ankle (76), hip and knee (31), elbow and shoulder (24), and spine (1). Seventy-four patients were treated with tocilizumab, 62 with etanercept, 55 with golimumab, 49 with abatacept, 16 with infliximab, 15 with adalimumab, and 6 with certolizumab. According to nutritional assessment in PNI and CONUT, 63% (n=175) and 47% (n=130) were normal nourished patients, respectively.In 277 procedures, DWH were identified in 24 patients (8.6%). The following variables were significant in the univariate analyses: disease duration (OR 1.053; 95% CI 1.010–1.099; p=0.016), foot and ankle surgery (OR 7.091; 95% CI 2.130–23.603; p=0.001), tocilizumab (OR 0.286; 95% CI 0.093–0.881; p=0.029) (Table 1). These variables were entered into a multivariate model, and it was revealed that pre-operative use of tocilizumab (OR 0.265; 95% CI 0.074–0.953; p=0.042) and procedures in the foot and ankle (OR 6.915; 95% CI 1.914–24.976; p=0.003) were associated with an increased risk of DWH (Table 1).Conclusion:As previous study on tocilizumab described, the current retrospective study suggested that pre-operative use of tocilizumab and procedures in the foot and ankle were risk factors for DWH. Pre-operative disease activity and nutritional status were not independent risk factors for an increase in the prevalence of DWH.References:[1] Momohara S, Hashimoto J, Tsuboi H et al. Analysis of perioperative clinical features and complications after orthopaedic surgery in rheumatoid arthritis patients treated with tocilizumab in a real-world setting: Results from the multicentre tocilizumab in perioperative period (TOPP) study. Modern rheumatology. 2013, 23: 440-9.Disclosure of Interests:Shunji Okita: None declared, Hajime Ishikawa: None declared, Asami Abe: None declared, Satoshi Ito Speakers bureau: Abbvie,Eisai, Akira Murasawa: None declared, Keiichiro Nishida Grant/research support from: K. Nishida has received scholarship donation from CHUGAI PHARMACEUTICAL Co., Eisai Co., Mitsubishi Tanabe Pharma and AbbVie GK., Speakers bureau: K. Nishida has received speaking fees from CHUGAI PHARMACEUTICAL Co., Eli Lilly, Janssen Pharmaceutical K.K., Eisai Co. and AYUMI Pharmaceutical Corporation., Toshifumi Ozaki: None declared

Background:Sarcopenia is characterized by loss of muscle mass and strength, which lead to lower physical ability, less quality of life (QoL), frailty and mortality. Rheumatoid arthritis (RA) is considered to be one of the causes of sarcopenia.Objectives:To clarify the effectiveness of biologic disease modifying anti-rheumatic drugs (bDMARDs) on sarcopenia, including physical ability, body composition and nutritional status.Methods:This is a prospective cohort study including consecutive 48 patients (male 11, female 37, age 64.2±15.1) with RA who started bDMARDs in Niigata Rheumatic Center. Diagnosis of sarcopenia was according to the diagnostic algorithm of European Working Group on Sarcopenia in Older People (EWGSOP). We monitored disease activity of RA, physical ability, body composition, nutritional status and QoL at baseline, 6 months and at 12 months. Disease activity was measured by disease activity score-28 joint count based on erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI). Physical activity was measured by Health Assessment Questionnaire (HAQ), 10m walking test (10MWT). Nutritional status was measured by controlling nutrition status (CONUT) score, and prognostic nutritional index (PNI). Overall QoL was measured by EuroQol 5 dimentions (EQ5D).Results:Among 48 patients who started bDMARDs, 21 patients were classified as having sarcopenia. The bDMARDs used were adalimumab in 10 cases, certolizumab pegol in 9 cases, abatacept in 9 cases, golimumab in 7 cases, tocilizumab in 5 cases, infliximab in 5 cases and etanercept in 3 cases. DAS28-ESR (4.7±1.4 vs. 2.7±1.0, p < 0.001) and CDAI (18.4±9.4 vs. 7.4±5.5, pConclusion:Twelve months of bDMARDs therapy significantly ameliorated disease activity, nutritional status and physical activity. In RA patients with sarcopenia, bDMARDs significantly increased skeletal muscle and may be effective for treatment of sacrcopenia.Disclosure of Interests: :Eriko Hasegawa: None declared, Satoshi Ito Speakers bureau: Abbvie,Eisai, Yoichi Kurosawa: None declared, Shinji Taniguchi: None declared, Daisuke Kobayashi: None declared, Asami Abe: None declared, Hiroshi Otani: None declared, Kiyoshi Nakazono: None declared, Akira Murasawa: None declared, Ichiei Narita: None declared, Hajime Ishikawa: None declared

Background:Although methotrexate is the anchor drug, it took some days to check contraindications, such as interstitial pneumonia, hepatitis B virus infection, and latent tuberculosis infection. Therefore, we sometimes start rheumatoid arthritis (RA) treatment with other disease-modifying antirheumatic drug (DMARD) in daily clinical setting. Iguratimod (IGU) is a newly developed DMARD approved in Japan in September 2012, and the efficacy of IGU for DMARD naïve patients has not been thoroughly evaluated.Objectives:The aim of this prospective single-center study was to demonstrate the efficacy and safety of IGU when used as a first-line daily DMARD for patients with RA in a clinical setting.Methods:Enrolled patients included those diagnosed with RA according to the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) classification criteria who took IGU as a first-line DMARD at Niigata Rheumatic Center between April 2016 and December 2018 (IGU group). There were no constraints regarding the addition or withdrawal of other DMARDs. Details of the patients’ background, clinical parameters, and laboratory findings were obtained, including C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), matrix metalloprotease-3 (MMP-3), rheumatoid factor (RF), Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire Disability Index (HAQ-DI). The efficacy of IGU was evaluated at week 24. The IGU group’s data were then compared with 64 patients who took salazosulfapyridine or bucillamine as first-line DMARD in our hospital (other DMARD group). The data were expressed as median values. Comparisons between the parameters were performed using nonparametric method.Results:Forty-three patients (15 males, 28 females) received IGU as a first-line DMARD for RA. The age was 69.0 years and the duration of disease was 2.0 months. Twenty patients received prednisolone (PSL) concomitantly at a median dose of 5.0 mg/day. At 24 weeks medications were utilized in patients as follows: IGU in 36 (83.7 %), methotrexate in 18 (41.2%), PSL in 17 (39.5%), BUC in 10 (23.2 %), and biological DMARD in 7 (15.2 %) patients. Although 7 patients discontinued taking IGU due to liver enzyme elevation (n=4), nausea (n=1), creatinine elevation (n=1), and skin rash (n=1) during the 24-week period, serious adverse events requiring hospitalization were not observed. Clinical parameters that improved from baseline after 24 weeks of treatment included: ESR from 42.0 mm/h to 16.0 mm/h with p < 0.001; CRP from 0.70 mg/dL to 0.10 mg/dL with p< 0.001; MMP-3 from 136 ng/mL to 91.5 ng/mL with a p value of 0.11; RF went from 18.0 IU/mL to 8.00 IU/mL with p < 0.001; DAS28(4)-ESR dropped from 5.13 to 2.73 with p< 0.001; CDAI dropped from 20.0 to 5.00 with p< 0.001, and HAQ-DI decreased from 0.55 to 0.00 with p< 0.001. Patients who achieved a good or moderate response based on EULAR response at 24 weeks, included 90.7% in the IGU group versus 70.5% in the other DMARD group (Fisher`s exact test, p=0.046). The retention rate of the IGU group was 81.4 %, roughly equivalent to the 81.2% retention rate in the other DMARD group (Log-rank test, p=0.733).Conclusion:Our study indicates IGU is safe and effective for DMARD naïve RA patients. Starting treatment with IGU might be a new and effective strategy for RA patients without previous use of a DMARD.Disclosure of Interests:Daisuke Kobayashi: None declared, Eriko Hasegawa: None declared, Yoko Wada: None declared, Satoshi Ito Speakers bureau: Abbvie,Eisai, Asami Abe: None declared, Kiyoshi Nakazono: None declared, Akira Murasawa: None declared, Ichiei Narita: None declared, Hajime Ishikawa: None declared

Background:Biological disease-modifying antirheumatic drugs (bDMARDs) caused a paradigm shift in the treatment of rheumatoid arthritis (RA). However, their high cost is a burden for patients and the national medical economy.Objectives:To analyze the long-term outcomes of patients with RA who achieved a bio-free condition (BF) with adalimumab (ADA).Methods:We followed 25 patients (male 6, female 19) who discontinued ADA with clinical remission (CR), and one female with a low disease activity (LDA), over 19.4 ±7.8 months of ADA treatment1). At the introduction of ADA, the average age was 51.2 ± 11.9 years old, and the average disease duration was 45.1 ± 48.4 months. The disease activity measured by disease activity score based on C-reactive protein (DAS28-CRP) was defined as follows: CR, 4.1, since the DAS28-CRP tends to be lower than the DAS28-based on the erythrocyte sedimentation rate in Japanese patients2).Results:We lost one patient with a transfer to another hospital. Four patients re-started ADA due to flare (DAS28-CRP>2.7) but achieved CR (in BF) again with the intensification of the treatment (dose increase or initiation of prednisolone [PSL] and/or conventional synthetic [cs] DMARDs such as tacrolimus or iguratimode). The DAS28-CRP significantly decreased from 3.45 ± 1.32 at base line (BL) to 1.55 ± 0.41 (pConclusion:BF can be sustained with an adequate dose of MTX and combination of csDMARDs.References:[1]Ito S, et al. An analysis of the biological disease-modifying antirheumatic drug-free condition of adalimumab-treated rheumatoid arthritis patients. Intern Med 58: 511-519, 2019[2]Inoue E, et al. Comparison of Disease Activity Score (DAS)28-erythrocyte sedimentation rate and DAS28- C-reactive protein threshold values. Ann Rheum Dis. 66:407-409, 2007.Disclosure of Interests:Satoshi Ito Speakers bureau: Abbvie,Eisai, Shunsuke sakai: None declared, Yoichi Kurosawa: None declared, Daisuke Kobayashi: None declared, Ryo Okabayashi: None declared, Asami Abe: None declared, Hiroshi Otani: None declared, Kiyoshi Nakazono: None declared, Akira Murasawa: None declared, Ichiei Narita: None declared, Hajime Ishikawa: None declared

Objectives The present study was performed with the aim of analyzing the biological disease-modifying antirheumatic drug (bDMARD)-free (Bio-free) condition of adalimumab (ADA)-treated rheumatoid arthritis (RA) patients in a real-world setting. Methods ADA was used in the treatment of 130 (male, n=21; female, n=109 females) RA patients. Among them, 26 patients (20.0%) discontinued ADA due to a good response. We analyzed 20 patients who were followed up for more than 6 months after the discontinuation of ADA. The Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) and modified health assessment questionnaires (mHAQs) were evaluated. Results The mean age of the patients was 53.4±11.1 years. The mean disease duration was 4.5±4.3 years. Sixteen patients were bDMARD-naive, while 4 switched from bDMARDs to ADA. At 6 months after the discontinuation ADA, 19 patients had achieved a clinical remission, and 1 had achieved a low disease activity. The Bio-free period was 26.4±15.5 months. The dose of prednisolone was significantly reduced from baseline (3.45±3.17 mg/day) at 6 months after the discontinuation of ADA (2.63±2.78 mg/day). The dose of methotrexate was unchanged. The number of conventional synthetic DMARDs (csDMARDs) was significantly increased (0.8±0.6 to 1.4±1.06). The mHAQ values were significantly ameliorated by ADA and remained good in patients with a Bio-free condition. A multivariate analysis showed that the dose of methotrexate (MTX) was an important factor for achieving a Bio-free condition. Conclusion A sustainable Bio-free condition in a real clinical setting can be achieved and may be a suitable way of reducing medical costs. The dose of MTX and the additional administration of csDMARDs is therefore thought to be important for ensuring a good outcome in these patients.

Background In the treatment of rheumatoid arthritis (RA), the early diagnosis and early medical treatment via tight control have become increasingly important with the advent of biological therapy. In addition, the existence of inflammation without bone destruction on magnetic resonance imaging has been found to be significantly associated with symptoms in the patient standpoint type inspection of early RA patients. Objectives This study was conducted to clarify the differences between the joint synovium and tendon sheath synovium, local disease activity using ultrasonography (US) and the findings on a synovial histopathological evaluation. Methods Between March 2011 and November 2017, 663 synovectomies were surgically treated, and synovial biopsies were performed at the time of surgery. Among them, 75 tendon sheath synovia and 588 joint synovia were investigated. A total of 81 men and 582 women were examined, with an average age of 64 years old. We examined the finger in 312 cases (39 tendons, 273 joints), wrist in 323 cases (33 tendons, 290 joints) and ankle in 28 cases (3 tendons, 25 joints). There were no cases with both tendon sheath synovium and joint synovium. Just before surgery, the US probe was placed on the dorsal and palmar/plantar aspect of the joint or the tendon sheath to evaluate the activity of local synovitis. The maximum grade of power Doppler (PD) signal was determined, ranging from 0 to 3. The serum C reactive protein (CRP), matrix metalloproteinase-3 (MMP-3) and DAS28 values were also examined just before surgery. A histopathological examination of the gathered synovium at the surgical site was performed using the Rooney score (RS). Results For the tendon sheath synovium, PD0, 14 cases; PD1, 32 cases; PD2, 19 cases and PD3, 10 cases were observed, with an average score of 1.33. For the joint synovium, PD0, 114 cases; PD1, 179 cases; PD2, 209 cases and PD3, 86 cases were observed, with an average score of 1.45. Regarding the DAS28, for the tendon sheath synovium, the average score was 3.59, and for the joint synovium, the average score was 3.61. Regarding the CRP, for the tendon sheath synovium, the average score was 0.64, and for the joint synovium, the average score was 0.66. Regarding the MMP-3, for the tendon sheath synovium, the average score was 113, and for the joint synovium, the average score was 123. There were no marked differences in the grade of PD, DAS28, CRP or MMP-3 between the synovia. The rate of synoviocytes hyperplasia did not differ between the synovia, but the rates of fibrosis and proliferating blood vessels were significantly high in the tendon sheath synovium, perivascular infiltrates of lymphocytes, focal aggregates of lymphocytes, diffuse infiltrates of lymphocytes was significantly high in joint synovium. Conclusions There was no marked difference in the US findings and the disease activity between the tendon sheath synovium and the joint synovium. However, there were differences in the local disease activities between the synovia. These results show that the tendon sheath synovium lacked acute inflammation. Disclosure of Interest None declared

Background Depression is the most frequently seen comorbidity in the patients with rheumatoid arthritis (RA) 1). Inflammatory mediators, including TNF-α, interleukin-1 and interleukin-6, affect serotonin transporters in the brain and promote low stress tolerance and depression 2). Objectives To investigate the effect of orthopaedic surgery on the mental condition of patients with RA by assessing the Beck depression inventory II (BDI-II) and to investigate the factors associated with changes in the BDI-II. Methods A prospective cohort study was performed in 294 sites of primary elective surgery in 276 patients with structural damage due to RA. The average (range) age was 6419–89 years old, and the average (range) disease duration was 161–60 years. The surgical site was the shoulder in 6 patients, elbow in 26, wrist in 74, hand in 63 (with wrist in 18), hip in 13, knee in 50, ankle in 12, and forefoot in 50. The BDI-II, EuroQol 5 dimensions (EQ-5D), Japanese version of the Stanford Health Assessment Questionnaire (J-HAQ), and disease activity score 28 using C-reactive protein4 (DAS28-CRP4) were assessed at the baseline and at 12 months after surgery. During the observational period, the number of patients using methotrexate (MTX), prednisolone (PSL), and biological disease-modifying anti-rheumatic drugs (bDMARDs) did not change significantly. The mean dose of MTX and PSL was reduced by 0.4 mg/w and 0.2 mg/d, respectively, at 12 months after surgery. Results In total, the mean BDI-II significantly improved from 13.0 to 11.5 at 12 months after surgery (p Conclusions Depression was ameliorated by surgical intervention in patients with RA. The mental condition is associated with the quality of life and physical function. References [1] Dougados M, et al. Ann Rheum Dis2014;73:62–8. [2] Mclnnes IB, Schett G. N Engl J Med2011;365:2205–19. [3] Ishikawa H. Orthop Sci. 2017;22:583–92. Disclosure of Interest None declared

Background Grip power is known to be a simple and useful objective index that can be used in the self-assessment of disease activity in patients with rheumatoid arthritis (RA) 1) . However, the clinical significance of this physical function is unknown. Objectives The objective of this study was to clarify the relationship between the grip power and the level of activities of daily living (ADL). Methods The grip power was measured in 221 inpatients of our hospital with RA using a mercury dynamometer. The independence level (0: impossible, 1: incomplete and not practical, 2: practical but the means thereof are unusual, 3: normal) for 44 ADL items, including most daily activities was investigated. For each item, the site with the problem (shoulder, elbow, forearm, wrist, thumb, fingers, lower extremity and trunk) and cause of disability (pain, loss of power, decreased range of motion, abnormal prehensile pattern and fatigue) were investigated by interviewing the patient. There were 33 male and 188 female patients. The average age of the patients was 64.6 years, and the average duration of the disease was 13.3 years. Biological therapy had been given to 23% of the patients. The average grip power of the right and left hands was used. Results There were 14 items requiring others’ assistance (level 0 or 1) in more than 10% of patients. For these 14 items of ADL, the grip power increased with the increase in the independence level (p 2 . The site with a problem was, in order of frequency, the fingers (26.1%), wrist (14.8%) and lower extremity (14.0%). The cause of disability was, in order of frequency, pain (38.8%), loss of power (32.8%) and a decreased range of motion. Based on the results of a stepwise regression analysis, the first factor, consisting mainly of “reaching function”, including “hair dressing”, “washing one’s body”, “taking on and off one’s shoes”, “clipping nails”, “buttoning”, etc., was most strongly related to a loss of grip power and problems at the elbow, the shoulder and the wrist. The second factor, consisting mainly of the “prehensile function”, including “opening a plastic bottle”, “opening lids”, “squeezing towels”, etc., was most strongly related to a loss of grip power and problems at the wrist and the thumb. The third factor, consisting mainly of “activities involving changing body position and transfer”, including “getting in and out of the bathtub”, “standing and sitting”, etc., was most strongly related to ageing and problems with the lower extremities and at the elbow and the wrist. In the receiver operating characteristic (ROC) curve, the grip power with the maximum Youden index was 136.5 mmHg (11.8 kg) in females and 152.5 mmHg (13.5 kg) in males. Most activities were performed independently with the grip power more than 136.5 mmHg in females (figure 1). The explanatory variables for the grip power in the female patients were ageing; a long disease duration; a high disease activity score (DAS) 28; problems at the fingers, the thumb and the elbow; decreased flexion at the shoulder and a decreased range of forearm rotation. Conclusions The grip power was a determinant of independent daily living in patients with RA in our study. References [1] Espinoza F, et al. Rheumatology (Oxford)2016;55:897–901. [2] Thyberg I, et al. Arthritis Rheum2005;53:886–96. Disclosure of Interest None declared

Objective To investigate the efficacy of minodronate in the treatment of glucocorticoid-induced osteoporosis (GIO). Methods The study population included patients in whom the administration of minodronate (50 mg, once every 4 weeks) had been newly started for the treatment of GIO in Niigata Rheumatic Center from 2012 to 2015. Patients who were bisphosphonate-naive and those who switched from other bisphosphonates were classified into the naive and switch groups, respectively. The changes in the bone mineral density (BMD) and bone metabolic markers after one year of minodronate treatment were retrospectively evaluated. We also compared the BMD and bone turnover marker changes of minodronate-naive patients with those in whom alendronate or risedronate had been prescribed as a first bisphosphonate (control group). Results Minodronate was prescribed to 142 patients, and data were successfully obtained from 120 patients. New vertebral fractures were observed in 5 of the 142 patients; 1 fracture occurred during the cessation of minodronate for dental treatment, and 3 patients already had multiple vertebral fractures before the initiation of minodronate. The patients' tartrate-resistant acid phosphatase 5b (TRACP-5b) (-27.0%, p

Although biological agents are of considerable benefit to patients with rheumatoid arthritis (RA), the potential for opportunistic infections is a critical issue. It is therefore important to achieve a balance between treatment efficacy and controlling opportunistic infection. We herein report the successfully managed case of a 53-year-old patient with RA who developed pulmonary Mycobacterium abscessus infection during treatment with tocilizumab and methotrexate.

Background Although the biological disease-modifying antirheumatic drugs (bDMARDs) are the most effective treatment for rheumatoid arthritis (RA), the costs are much higher than those of conventional synthetic DMARDs. A number of studies on discontinuation, dose reduction and/or spacing of bDMARDs have been performed, but there have been few reports on increased spacing time between tocilizumab (TCZ) administrations so far. Objectives To analyze the efficacy of spacing of the intravenous (IV) administration of TCZ in patients with RA. Methods 63 patients (11 M, 52 F) who were administered IV TCZ for more than 1 year were enrolled. Eleven patients had shifted to subcutaneous injection and the data at the last IV infusion were analyzed. Results Mean age was 57.4 years old (30–78), mean body weight was 55.5kg (37–85.5), mean duration of illness was 10.7yrs (0–32), The number of the bDMARDs previously administered were 0.9 (0–3), and duration of TCZ treatment was 46.9 months (13–83). The intervals between administrations were 4 weeks: 28.6%, 5 weeks: 38.1%, 6 weeks: 17.5%, 7 weeks: 6.0%, 8 weeks: 7.9%, and 10 weeks: 1.6%. Tender joint count, swollen joint count, erythrocyte sedimentation rate (ESR), C-reactive protein, matrix metalloproteinase-3 (MMP-3), patient9s visual analogue scale (VAS), doctor9s VAS, disease activity score (DAS) 28-ESR, simplified disease activity index (SDAI), clinical DAI (CDAI) were significantly improved. All of patients remission rates were 90.5% for DAS28-ESR, 44.4% for CDAI, and 42.9% for SDAI. Patients with prednisolone (PSL) decreased from 50 to 38 (p=0.031), at doses of 5.3 (2–10) to 2.7 (0.5–5) mg/day (p Conclusions TCZ treatment was associated with significantly reduced disease activity and reduced use of PSL and MTX. Increased spacing between administrations was used in 71.4% of the patients. TCZ was able to reduce PSL and MTX even after spacing. MMP-3 might be a useful marker to decide the spacing period. TCZ is the most inexpensive bDMARD in Japan, but with increased spacing, it is possible to reduce the cost even further with acceptable control of RA symptoms. Disclosure of Interest None declared

Background The hand is the most frequently involved site in rheumatoid arthritis (RA). The treatment aim of RA is achieving and maintaining remission (REM) or low disease activity (LDA) via tight medical control. However, despite remarkable advances in medication, progressive deterioration and/or deformity of the hand, if adequate medication is not administered in the early stage. Surgical reconstruction is still required in hands with functional loss and/or a grotesque appearance caused by joint deterioration or tendon rupture. Recently, patients have expressed a desire to achieve functional REM with a higher quality of life (QOL) and improved mental wellness. Objectives The objective of this study was to clarify the systemic effects of surgical intervention in the impaired hand, even in patients with well-controlled disease who have achieved REM or LDA. Methods A prospective cohort study was performed in 119 hands of 119 patients with functional loss and/or a grotesque appearance due to RA who underwent primary elective surgery between October 2012 and September 2014. A total of 42 hands in 42 patients (males: 2, females: 40) had a disease activity of REM or LDA just before surgery. In the REM/LDA group, the average (range) age was 61 (29–82) years, and the average (range) disease duration was 15 (2–35) years. The procedures performed included Darrach procedure (ulnar head resection) in 17 hands, radiolunate arthrodesis in 10, extensor tendon reconstruction in 6, thumb/finger metacarpophalangeal joint arthroplasty (Swanson) in 14, proximal interphalangeal (interphalangeal) joint fusion in 4, and thumb CM joint arthroplasty (Thompson) in 4 and so on. The patient-reported outcome (PRO) was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI), EuroQol-5 Dimensions (EQ-5D), Beck Depression Inventory-II (BDI-II), Patient9s General Health using visual analogue scale of 100 mm (Pt-GH), and the Disabilities of the Arm, Shoulder and Hand (DASH). The 28-joint Disease Activity Score using C reactive protein (DAS28-CRP) and Grip power (GP) were also examined. All of these items were investigated just before surgery (baseline) and again at 6 and 12 months after surgery. Results On the whole, the physical function (HAQ-DI, DASH, GP), QOL (HAQ-DI, EQ-5D, Pt-GH), mental wellness (BDI-II, Pt-GH), and disease activity (DAS28-CRP) were significantly improved at 6 and 12 months after surgery compared to baseline (p Conclusions Achieving REM or LDA is not the ultimate goal of treatment for patients with functional loss and/or a grotesque appearance of their hands. Further “wellness” can be achieved by surgical intervention in the affected hand, even for patients with well-controlled RA. Such intervention can also ameliorate the disease activity. References Ishikawa H, Murasawa A, Nakazono K, et al. The patient-based outcome of upper-extremity surgeries using the DASH questionnaire and the effect of disease activity of the patients with rheumatoid arthritis. Clin Rheumatol. 2008;27:967–973. Disclosure of Interest None declared

Background The treatment aim of rheumatoid arthritis (RA) is achieving and maintaining remission (REM) or low disease activity (LDA) via tight medical control 1) . However, despite remarkable advances in medication, progressive deterioration and deformity of the forefoot sometimes occur if adequate medication is not administered in the early stage. Surgical reconstruction is still required in patients with painful callosity and footwear problems caused by typical forefoot deformity. Recently, patients have expressed a desire to achieve functional REM with a higher quality of life (QOL) and improved mental wellness. Objectives The objective of this study was to clarify the systemic effects of forefoot reconstruction on the impaired foot, even in patients who have achieved REM or LDA. Methods A prospective cohort study was performed for 63 feet of 50 patients (males: 6, females: 44) with RA who underwent primary elective surgery between October 2012 and September 2014. Both feet underwent surgery on the same day in 13 patients. The average (range) age was 64 (42–89) years, and the average (range) disease duration was 20 (2–36) years. The procedures performed included shortening oblique osteotomy at the metatarsal neck of the lessor toes in 47 feet, first metatarsophalangeal joint arthroplasty (Swanson) in 44 feet, correction shortening osteotomy (modified Mitchell) at the first metatarsal in 4 feet, and fusion at the first interphalangeal joint in 7 feet, among others. A total of 30 feet in 27 patients (males: 5, females: 22) had a disease activity of REM or LDA just before surgery. The patient-reported outcomes (PROs) were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI), EuroQol-5 Dimensions (EQ-5D), Beck Depression Inventory-II (BDI-II), and Patient9s General Health using a visual analogue scale of 100 mm (Pt-GH). The 28-joint Disease Activity Score using C reactive protein (DAS28-CRP), the Japanese Society of Surgery of the Foot (JSSF) standard rating system (JSSF) for the RA foot and ankle scale 2) , and the Time Up&Go test (TUG) were also evaluated. All of these items were investigated just before surgery (baseline) and again at 6 and 12 months after surgery. Results Overall, the physical function (JSSF, TUG), QOL (EQ-5D), and mental wellness (depression) (BDI-II) were significantly improved at 6 and 12 months after surgery compared to the baseline values (p Conclusions Achieving REM or LDA is not the ultimate goal of treatment for patients with painful callosity and footwear problem functional loss. A higher QOL and improved function can be achieved by surgical intervention in the deformed forefoot. References Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75(1):3–15. Niki H, Aoki H, Inokuchi S, et al. Development and reliability of a standard rating system for outcome measurement of foot and ankle disorders I: development of standard rating system. J Orthop Sci. 2005:10:457–465. Disclosure of Interest None declared

Although biological agents are of considerable benefit to patients with rheumatoid arthritis (RA), the potential for opportunistic infections is a critical issue. It is therefore important to achieve a balance between treatment efficacy and controlling opportunistic infection. We herein report the successfully managed case of a 53-year-old patient with RA who developed pulmonary Mycobacterium abscessus infection during treatment with tocilizumab and methotrexate.

OBJECTIVE: The aim of this study was to analyze the efficacy of adalimumab (ADA) in patients with rheumatoid arthritis treated with or without methotrexate (MTX) and determine impact of the MTX dose. METHODS: Pearson's product-moment correlation coefficient was used to assess the correlations between the improvement in the Disease Activity Score (DAS) 28- erythrocyte sedimentation rate (ESR) score and the MTX dose in patients receiving treatment with MTX at a dose of 8 mg/week. PATIENTS: ADA therapy was initiated in 68 rheumatoid arthritis patients between July 2008 and June 2013. The mean MTX dose was 9.6 ± 2.6 mg/week, and the patients were followed for 24 weeks. RESULTS: The mean DAS28-ESR scores at baseline and week 24 were 4.6 ± 1.3 and 2.7 ± 1.2 in the 60 patients treated with MTX and 4.5 ± 1.0 and 4.2 ± 1.5 in the eight patients treated without MTX, respectively. Clinical remission was achieved in 48% and 25% of the patients, respectively, by week 24. Moreover, 90.0% of the patients taking MTX continued to receive ADA until week 24, while 50.0% of the patients not taking MTX continued to receive ADA until week 24. Among the 35 patients receiving MTX at a dose of >8 mg/week, the DAS28-ESR scores decreased rapidly from 4.4 ± 1.2 at baseline to 3.2 ± 1.1 at week 4 and further decreased to 2.4 ± 1.0 at week 24. Meanwhile, clinical remission was achieved in 57% of the patients receiving MTX at a dose of >8 mg/week and 36% of those receiving MTX at a dose of ≤8 mg/week. A significant correlation was noted between the improvement in the DAS-ESR score and the MTX dose. CONCLUSION: In this study population, enhanced clinical efficacy of ADA was achieved in combination with the administration of a sufficient dose of MTX, determined to be >8 mg/week.

Transgenic rats expressing the env-pX gene of human T cell leukemia virus type-I under the control of the viral long terminal repeat promoter (env-pX rats) developed systemic autoimmune diseases. Prior to disease manifestation, the immunosuppressive function of CD25(+)CD4(+) T (T-reg) cells was impaired in these rats. Since T cell differentiation appeared to be disordered in env-pX rats, we assumed that the impairment of T-reg cells might be caused by an abortive differentiation in the thymus. However, reciprocal bone marrow transfers between env-pX and wild-type rats revealed that direct effects of the transgene unrelated to the thymus framework induced the abnormality of T-reg cells. To identify molecular changes, comparative analyses were done between env-pX and wild-type T-reg cells. Expression of the Foxp3 gene and cell-surface markers supported a naive phenotype for env-pX T-reg cells. Array analyses of gene expression showed some interesting profiles, e.g. up-regulation of genes associated with the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways in env-pX T-reg cells. Additionally, expression of the suppressor of cytokine signaling (SOCS) family genes, which inhibit the JAK/STAT signals, was extremely low in env-pX T-reg cells. These findings suggest that the transgene may mediate the down-regulation of the SOCS family genes and that subsequent excess signals through the JAK/STAT pathways may result in the loss of function of env-pX T-reg cells. We suggest that investigation of the pathology of T-reg cells in our autoimmune-prone rat model may aid in understanding the roles of T-reg cells in human autoimmune diseases.

Necrotizing arteritis mimicking polyarteritis nodosa occurred in transgenic rats carrying the env-pX gene of human T-cell leukemia virus type I. To investigate the pathogenesis of necrotizing arteritis in these rats (env-pX rats), adoptive transfers of spleen cells and bone marrow cells were done from env-pX rats before they developed arteritis to nontransgenic rats. Necrotizing arteritis occurred in lethally irradiated nontransgenic rats reconstituted by env-pX spleen cells, thus indicating that the env-pX transgene in affected vessels may not be essential for the development of arteritis. In contrast, arteritis was not induced in nontransgenic recipients by adoptive transfers of env-pX bone marrow cells, which suggested that T cells derived from the env-pX thymus may play a role in the development of arteritis. To clarify if the process of differentiation of T cells in the env-pX thymus is crucial to develop necrotizing arteritis, reciprocal exchange of thymus frameworks was done between env-pX and nontransgenic rats. Necrotizing arteritis occurred in nontransgenic rats with an env-pX thymus framework, whereas development of arteritis was suppressed in env-pX rats in which the thymus framework was replaced with a nontransgenic one. This collective evidence shows that the thymus is directly associated with the development of necrotizing arteritis in env-pX rats.

Background Multiple sclerosis is a relatively rare disease, and complications of multiple sclerosis and rheumatoid arthritis are much rarer. Since anti-tumor necrosis factor therapy increases exacerbations of multiple sclerosis, complications of demyelinating diseases contraindicate anti-tumor necrosis factor therapy. There have been few reports of anti-interleukin-6 receptor therapy for patients with rheumatoid arthritis complicated with multiple sclerosis. Case presentation A 53-year-old Japanese woman with multiple sclerosis and rheumatoid arthritis was admitted to our hospital because her rheumatoid arthritis was uncontrolled with oral methotrexate, tacrolimus, and prednisolone. She had developed multiple sclerosis when she was 25 years old and was treated with glucocorticoid therapy. Her multiple sclerosis was in remission for more than 9 years. Because anti-tumour necrosis factor therapy can exacerbate demyelinating disease, the anti-interleukin-6 receptor antibody tocilizumab was started at 8 mg/kg every 4 weeks. At the second administration of tocilizumab, complete remission was achieved. She has remained in remission with tocilizumab without recurrence of multiple sclerosis for more than 5 years. Conclusion Anti-interleukin-6 therapy was safely used in this patient with rheumatoid arthritis without exacerbations of multiple sclerosis.

Gamma-aminobutyric acid (GABA) is an important neurotransmitter, but recent reports have revealed the expression of GABAergic components in peripheral, non-neural tissues. GABA administration induces natriuresis and lowers blood pressure, suggesting renal GABA targets. However, systematic evaluation of renal GABAergic components has not been reported. In this study, kidney cortices of Wistar-Kyoto rats (WKY) were used to assay for messenger RNAs of GABA-related molecules using RT-PCR. In WKY kidney cortex, GABAA receptor subunits, α1, β3, δ, e and π, in addition to both types of GABAB receptors, R1 and R2, and GABAC receptor ρ1 and ρ2 subunit mRNAs were detected. Kidney cortex also expressed mRNAs of glutamate decarboxylase (GAD) 65, GAD67, 4-aminobutyrate aminotransferase and GABA transporter, GAT2. Western blot and/or immunohistochemistry were performed for those molecules detected by RT-PCR. By immunofluorescent observation, co-staining of α1, β3, and π subunits was observed mainly on the apical side of cortical tubules, and immunoblot of kidney protein precipitated with π subunit antibody revealed α1 and β3 subunit co-assembly. This is the first report of GABAA receptor π subunit in the kidney. In summary, unique set of GABA receptor subunits and subtypes were found in rat kidney cortex. As GABA producing enzymes, transporters and degrading enzyme were also detected, a possible existence of local renal GABAergic system with an autocrine/paracrine mechanism is suggested.

Objective.Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by many complications, and serious infections are associated with many of the advanced therapeutics used to treat it. We assessed serum procalcitonin (PCT) levels to distinguish bacterial infection from other complications in patients with RA.Methods.One hundred eighteen patients experiencing an RA flare, noninfectious complication of RA or its treatment, nonbacterial infection, or bacterial infection were studied. Serum PCT concentrations were determined with a chemiluminescent enzyme immunoassay.Results.All patients experiencing an RA flare showed negative PCT levels (≤ 0.1 ng/ml; n = 18). The PCT level was higher in the bacterial infection group (25.8% had levels ≥ 0.5 ng/ml) than in the other 3 groups (0.0–4.3% had levels ≥ 0.5 ng/ml) and the difference was significant among groups (p = 0.003). Conversely, no statistically significant difference was observed among the groups with C-reactive protein (CRP) concentration ≥ 0.3 mg/dl (p = 0.513), white blood cell (WBC) count > 8500/mm3 (p = 0.053), or erythrocyte sedimentation rate (ESR) > 15 mm/h (p = 0.328). The OR of high PCT level (≥ 0.5 ng/ml) for detection of bacterial infection was 19.13 (95% CI 2.44–149.78, p = 0.005). Specificity and positive likelihood ratio of PCT ≥ 0.5 ng/ml were highest (98.2% and 14.33, respectively) for detection of bacterial infection, although the sensitivity was low (25.8%).Conclusion.Serum PCT level is a more specific marker for detection of bacterial infection than either CRP, ESR, or WBC count in patients with RA. High PCT levels (≥ 0.5 ng/ml) strongly suggest bacterial infection. However, PCT < 0.5 ng/ml, even if < 0.2 ng/ml, does not rule out bacterial infection and physicians should treat appropriately.

DAP12 is a recently cloned, immunoreceptor tyrosine-based activation motif-bearing transmembrane adapter molecule that is associated with the NK-activating receptors. Previous reports showed that the DAP12 message could be detected not only in NK cells but also in granulocytes, monocytes, dendritic cells, and macrophages. In this study we found a significant level of DAP12 protein expression in macrophage-related cell lines and organs. Additionally, we observed increased expression of DAP12 after LPS-induced differentiation of M1 cells into macrophages. To examine the role of DAP12 in the myeloid cell lineage, we established M1 FLAG-DAP12 transfectants (FDAP-M1) and demonstrated the marked morphological changes in FDAP-M1 cells caused by signaling through DAP12. Cell surface phenotypic analysis showed up-regulation of macrophage markers CD11b, 2.4G2, and adhesion molecule B7-2. Additionally, after stimulation through DAP12, phosphorylated FLAG -DAP12 could be immunoprecipitated using anti-phosphotyrosine mAbs. Collectively, these findings indicate that direct DAP12 signaling has an important role in macrophage differentiation.

Transgenic rats carrying the env-pX gene of human T-cell leukaemia virus type-I (env-pX rats) were immunized with type II collagen (CII), and chronological alterations of arthritis were compared with findings of collagen-induced arthritis (CIA) in wildtype Wistar-King-Aptekman-Hokudai (WKAH) rats. Arthritis induced by CII in env-pX rats was more severe and persisted longer than CIA in WKAH rats. To determine whether the phenomenon is caused mainly by the transgene-carrying lymphocytes or articular tissues, we immunized lethally irradiated env-pX and WKAH rats with reciprocal bone marrow cell (BMC) transplantation. A severe but transient arthritis was induced by CII in WKAH rats reconstituted by env-pX BMC (w/tB/CII rats). On the other hand, in env-pX rats reconstituted by WKAH BMC, arthritis persisted longer than in w/tB/CII rats, although the degree was less at an early phase after CII immunization. These findings suggest that articular tissues rather than the BMCs carrying the env-pX transgene play a role in the prolongation of arthritis in env-pX rats, although BMCs carrying the transgene are associated with the severity of arthritis. When inflammatory cytokines in synovial cells isolated from env-pX rats before they developed arthritis were examined, interleukin-6 (IL-6) was detected at a higher level than in synovial cells from WKAH rats, thus suggesting the critical role of IL-6 in env-pX arthritis.