論文

© Copyright 2017. All rights reserved. Objective. To assess the utility of dose frequency adjustment of tocilizumab (TCZ) in rheumatoid arthritis (RA). Methods. Patients who received TCZ at 3-week (n = 24) or 5-week (n = 61) interval were evaluated. Results. Disease Activity Score at 28 joints based on erythrocyte sedimentation rate in the 3-week group significantly improved after 3 administrations at 3-week intervals (from 4.2 to 2.7, p = 0.001). Forty-five of the patients in the 5-week group (74%) successfully continued 5-week interval administration without disease exacerbation. Lower C-reactive protein level at TCZ initiation and shorter duration to remission achievement were key to successful dose frequency reduction. Conclusion. Adjusting the dose frequency of intravenous TCZ is a useful strategy.

Copyright © 2016. All rights reserved. Objective. To assess toreforant (selective histamine H 4 receptor antagonist) in active rheumatoid arthritis (RA). Methods. In a phase IIa, double-blind, placebo-controlled test, 86 patients were randomized (2:1) to once-daily toreforant 100 mg or placebo for 12 weeks. In phase IIb, double-blind, placebo-controlled, dose-range-finding evaluations, 272 patients were randomized (1:1:1:1) to once-daily placebo or toreforant 3/10/30 mg. Primary efficacy endpoints for both studies were Week 12 changes in 28-joint Disease Activity Score-C-reactive protein (DAS28-CRP). Results. Phase IIa testing was terminated prematurely (patient fatality; secondary hemophagocytic lymphohistiocytosis). Posthoc analyses indicated toreforant 100 mg/day reduced RA signs/symptoms through Week 12. Phase IIb testing, however, showed no significant Week 12 improvement in DAS28-CRP with toreforant. Conclusion. Toreforant was not effective in phase IIb testing.

© 2016 Yamanaka et al. Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented. Methods: Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate. Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treatment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate (ESR))<2.6 response rate (DAS-defined remission) and Health Assessment Questionnaire-Disability Index (HAQ-DI) score. Safety and efficacy data were assessed throughout the study. Results: A total of 486 patients were recruited and treated (1439.9 patient-years of exposure). 308 patients completed the study. Median (range) duration of treatment in this extension study was 1185 (5-2016) days. 476 patients (97.9 %) experienced adverse events; the majority of which (97.8 %) were of mild or moderate severity. The two most common treatment-emergent adverse events were nasopharyngitis (n = 293, 60.3 %) and herpes zoster (n = 94, 19.3 %). For all tofacitinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding non-melanoma skin cancer). Mean changes from baseline (start of the index study) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib. ACR20/50/70 response rates, DAS-defined remission rates and HAQ-DI scores were sustained through to study completion. Conclusions: Tofacitinib (with or without background methotrexate) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis. The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population. Trial registration: Clinicaltrials.gov NCT00661661. Registered 7 February 2008.

Polymyalgia rheumatica (PMR) affects older people, and although glucocorticoids are effective in treating PMR, they frequently result in side effects. Therefore, we conducted a retrospective study to assess the effectiveness and safety of tocilizumab as an alternative to glucocorticoids. We included 13 consecutive patients with PMR (11 women and 2 men; median age, 74 years) diagnosed according to Bird's criteria and the 2012 European League Against Rheumatism/ American College of Rheumatology provisional classification criteria. All patients received tocilizumab infusion (8 mg/kg every 4 weeks) at our institutions, between 2008 and 2014, because of PMR relapses (n=12) or insufficient response to initial prednisolone treatment (n=1), without increasing prednisolone dosage. Seven patients were on methotrexate, and all had one or more glucocorticoid-related comorbidities. Administration of tocilizumab significantly improved inflammation and PMR symptoms such as morning stiffness, as well as the Patient-Pain and Patient-Global Assessment visual analogue scales ( p<0.05). Proximal muscle pain disappeared within 8 weeks, on average, and the Health Assessment Questionnaire-Disability Index scores (p=0.098) and concomitant prednisolone doses (p<0.05) decreased at 12 weeks. Severe adverse events were not observed during the mean tocilizumab treatment period of 43.4 weeks. Our findings suggest that tocilizumab is effective and safe for PMR treatment.

© 2015 Japan College of Rheumatology. Objectives. To investigate the relationship between changes in patient characteristics over time and the eff ectiveness and safety of adalimumab in the treatment of rheumatoid arthritis (RA) in clinical practice. Methods. Patients enrolled in the post-marketing registry study in Japan were divided into 5 subgroups based on the time adalimumab treatment was initiated. Demographic and baseline characteristics and responses to adalimumab were compared among the 5 subgroups to detect any time-course trend. Multiple logistic regression analysis was performed to identify characteristics that were signifi cantly associated with the eff ectiveness or safety of adalimumab and to estimate response rates and the incidence of adverse drug reactions in individual subgroups. Results. During the study period, patient characteristics changed signifi cantly over time, in particular with regard to prior biologic use and concomitant methotrexate therapy. There was a signifi cant trend toward higher response rates and lower incidence of infections and injection-site reactions in patients initiating adalimumab later in the study. Patient characteristics, such as concomitant methotrexate therapy and early stage RA, were signifi cant predictors of the eff ectiveness and safety of adalimumab. Conclusions. Patient characteristics have changed since adalimumab became available for the treatment of RA; several of these characteristics were signifi cant predictors of adalimumab eff ectiveness and safety.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights.OBJECTIVE: To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion.METHODS: A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived.RESULTS: The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10).CONCLUSIONS: The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

Background: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. Objective: To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. Methods: A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. Results: The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10). Conclusions: The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Background Treatment of rheumatoid arthritis (RA) with a combination of methotrexate (MTX)+adalimumab (ADA) is more effective than ADA monotherapy. We assessed the toxicity of different doses of MTX and treatment efficacy of ADA+MTX in two trials. Methods Data originated from CONCERTO, in patients with early RA initiating ADA+ 2.5, 5, 10 or 20 mg/week MTX for 26 weeks; and MUSICA, in patients with an inadequate response to MTX initiating ADA+ 7.5 or 20 mg/week MTX for 24 weeks. Efficacy was assessed by the American College of Rheumatology 50 (ACR50). Patient-reported MTX-related toxicity information was collected at each visit on 18 prespecified MTX-related adverse events (AE) in the MTX label. Results In CONCERTO, ACR50 rates increased over time, ranging from 54% to 68% at week 26, while AE rates remained steady, ranging from 2.4% to 17.8% at week 26. Of 395 patients, 113 (28.6%) reported 345 MTX-related AEs, including one serious AE (SAE, excessive fatigue and/or malaise); 10 AEs (in two patients) led to study discontinuation. In MUSICA, ACR50 rates increased over time, and were 32.3% and 37.5% at week 24, while MTX-related AE rates remained steady and were 6.5% at week 24. Of 309 patients, 71 (23%) reported 185 MTX-related AEs, including 5 SAEs (four infections and one fever/chills); six AEs (in four patients) led to study discontinuation. Conclusion In patients with RA initiating ADA+MTX combination, treatment efficacy was achieved and increased throughout both trials, while rates of MTX-related AEs remained steady. MTX-related AEs were observed in up to 30% of patients and most were mild. MTX was discontinued by 0.5%-1.3% of patients. Trial registration number MUSICA (NCT01185288), CONCERTO (NCT01185301), Post results.

© 2017 The Japan Academy. Molecules involved in the disease process facilitated our understanding of pathogenesis of the disease with unknown etiology such as immune-mediated and inflammatory diseases. Moreover, the targeted therapies against the proposed molecular targets by biological agents provide enormous benefits to the patients and societies. Here, I will review recent progress of the biological treatment in the immune-inflammatory diseases by focusing on the rheumatoid arthritis, the disease characterized by persistent polyarthritis leading to joint destruction and disability with autoimmune features, as a role model.

Objective: Autoantibodies to aminoacyl-tRNA synthetases (ARSs) are useful in the diagnosis of idiopathic inflammatory myopathy (IIM) with interstitial pneumonia (IP). We developed an enzyme-linked immunosorbent assay (ELISA) system using a mixture of recombinant ARS antigens and tested its utility in a multicenter study. Methods: We prepared six recombinant ARSs: GST-Jo-1, His-PL-12, His-EJ and GST-KS expressed in Escherichia coli, and His-PL-7 and His-OJ expressed in Hi-5 cells. After confirming their antigenic activity, with the exception of His-OJ, we developed our ELISA system in which the five recombinant ARSs (without His-OJ) were mixed. Efficiency was confirmed using the sera from 526 Japanese patients with connective tissue disease (CTD) (IIM n = 250, systemic lupus erythematosus n = 91, systemic sclerosis n = 70, rheumatoid arthritis n = 75, Sjögren's syndrome n = 27 and other diseases n = 13), 168 with idiopathic interstitial pneumonia (IIP) and 30 healthy controls collected from eight institutes. IIPs were classified into two groups; idiopathic pulmonary fibrosis (IPF) (n = 38) and non-IPF (n = 130). Results were compared with those of RNA immunoprecipitation. Results: Sensitivity and specificity of the ELISA were 97.1% and 99.8%, respectively when compared with the RNA immunoprecipitation assay. Anti-ARS antibodies were detected in 30.8% of IIM, 2.5% of non-myositis CTD, and 10.7% of IIP (5.3% of IPF and 12.3% of non-IPF). Anti-ARS-positive non-IPF patients were younger and more frequently treated with glucocorticoids and/or immunosuppressants than anti-ARS-negative patients. Conclusion: A newly established ELISA detected anti-ARS antibodies as efficiently as RNA immunoprecipitation. This system will enable easier and wider use in the detection of anti-ARS antibodies in patients with IIM and IIP. © 2014 Nakashima et al.

Tumor necrosis factor (TNF) inhibitors have produced improvements in clinical, radiographic, and functional outcomes in rheumatoid arthritis (RA) patients. However, it remains unclear whether factors affecting physical functions remain following TNF therapy. The objective of our study was to assess factors affecting improvement of physical functions and to shed light on relations to disease activity and structural changes in patients with RA treated with etanercept. The study enrolled 208 patients, all of whose composite measures regarding clinical, radiographic, and functional estimation both at 0 and 52 weeks after etanercept therapy were completed. Mean disease duration of 208 patients was 9.6 years, mean Disease Activity Score for 28 joints (DAS28) was 5.4, and mean van der Heijde modified total Sharp score (mTSS) was 94.6. Mean Health Assessment Questionnaire Disability Index (HAQ-DI) improved from 1.4 at 0 weeks to 1.0 at 52 weeks after etanercept therapy, a 31% reduction, which was much less than changes in DAS28 and mTSS. By multivariate analysis, HAQ-DI and mTSS at baseline were significantly correlated HAQ remission. Median HAQ-DI improved in 100 versus 20% of the HAQ-DI ≤0.6 versus ≥2.0 groups, respectively. The mTSS cutoff point at baseline to obtain HAQ remission was 55.5. During etanercept treatment in the mTSS <55.5 versus >55.5 groups, median HAQ-DI improved in 70 versus 39%; remission was achieved in 59 versus 33%; and there was no improvement in 14 versus 30%, respectively. HAQ-DI improvement was significantly correlated with that of DAS28 but not of mTSS. In conclusion, higher HAQ and mTSS at baseline inhibits HAQ-DI improvement within 1 year of etanercept treatment, and the cutoff point necessary for mTSS to improve physical functions in patients with RA was 55.5. © Japan College of Rheumatology 2011.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology. Recently, it has been reported that quite a few cases of refractory AOSD were successfully treated with tocilizumab (TCZ) and corticosteroids were withdrawn in some of these patients. We report two AOSD patients who were treated successfully with TCZ monotherapy; thus, avoiding corticosteroid treatment. Because both of the patients refused to take corticosteroids, we planned to treat them with 8 mg/kg of TCZ monotherapy at weeks 0, 2, 6 and subsequently every 4 weeks. The efficacy of TCZ was assessed by patients' clinical symptoms such as fever, arthralgia, skin eruptions, and laboratory markers such as serum levels of CRP, ferritin, and IL-6. We also reviewed 14 previous case reports including 30 cases who had been treated with TCZ for AOSD. Our patients responded rapidly and have been maintained in clinical remission without corticosteroid treatment. In the literature review, concomitant corticosteroid treatment described in 13 cases was successfully tapered in 7 and discontinued in 6 cases. TCZ monotherapy can be a candidate for the first-line therapy for some AOSD patients. © 2011 Clinical Rheumatology.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Objectives Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases in which both genetic and environmental factors play important roles. To identify genetic factors of IIM including polymyositis, dermatomyositis (DM) and clinically amyopathic DM (CADM), we performed the first genome-wide association study for IIM in an Asian population. Methods We genotyped and tested 496 819 single nucleotide polymorphism for association using 576 patients with IIM and 6270 control subjects. We also examined the causal mechanism of disease-associated variants by in silico analyses using publicly available data sets as well as by in in vitro analyses using reporter assays and apoptosis assays. Results We identified a variant in WDFY4 that was significantly associated with CADM (rs7919656; OR=3.87; P=1.5×10 -8). This variant had a cis-splicing quantitative trait locus (QTL) effect for a truncated WDFY4isoform (tr-WDFY4), with higher expression in the risk allele. Transexpression QTL analysis of this variant showed a positive correlation with the expression of NF-ΚB associated genes. Furthermore, we demonstrated that both WDFY4 and tr-WDFY4 interacted with pattern recognition receptors such as TLR3, TLR4, TLR9 and MDA5 and augmented the NF-ΚB activation by these receptors. WDFY4 isoforms also enhanced MDA5-induced apoptosis to a greater extent in the tr-WDFY4-transfected cells. Conclusions As CADM is characterised by the appearance of anti-MDA5 autoantibodies and severe lung inflammation, the WDFY4 variant may play a critical role in the pathogenesis of CADM.

© Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2018. Objective. To identify biomarkers for disease activity in IgG4-related disease (IgG4-RD) and primary Sjögren's syndrome (pSS). Methods. Forty-three consecutive treatment- naïve patients with IgG4-RD, 62 patients with pSS, and 5 patients with sicca syndrome were enrolled. IgG4-RD and pSS disease activity was assessed based on the IgG4-RD responder index (IgG4-RD RI) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), respectively. The associations of biomarkers with disease activity were examined. Results. Comparison of the three diseases identified the serum levels of IgG, IgG4, IgG4/IgG ratio, IgE, and soluble interleukin-2 receptor (sIL-2R) for IgG4-RD and the serum levels of IgM and sIL-2R and lymphocyte counts for pSS as potential biomarkers of disease activity. Among these, serum sIL-2R levels correlate with baseline IgG4-RD RI scores and the number of affected organs in IgG4-RD (p=0.74, p<0.0001 and p=0.75, p<0.0001, respectively). Serum sIL-2R levels also correlate with ESSDAI scores and the number of affected organs in pSS (P=0.67, p<0.0001 and p=0.41, p<0.0001, respectively). Receiver operating characteristic curve analysis suggested serum sIL-2R levels as an efficient biomarker to distinguish the presence of extra-dacryosialadenitis involvements in IgG4-RD with a cut-off value of 424 U/mL (AUC=0.93, p<0.0001), and in pSS with 452 U/mL (AUC=0.89, p<0.0001). Serum sIL-2R levels decreased significantly after treatment in patients with IgG4-RD and pSS. Conclusion. Serum sIL-2R levels are a potentially valuable biomarker for evaluating disease activity and treatment response in IgG4-RD and pSS.

© 2016 Japan College of Rheumatology. Objective: To evaluate association of clinical remission at month 6 with functional and structural remissions at month 12 during abatacept treatment in patients with rheumatoid arthritis (RA). Methods: This 12-month prospective, multicenter cohort study enrolled 168 patients with RA who started abatacept. Outcomes were assessed using composite measures, quality of life indices, and the van der Heijde-modified total Sharp score (mTSS). The logistic regression analysis was applied to identify factors associated with outcomes and their odds ratios (OR) with 95% confidence interval (95% CI). Results: At month 6 and 12, 21.4% and 26.2% of the patients achieved Simplified Disease Activity Index (SDAI) remission (SDAI <3.3), and 40.6% and 41.7% achieved Health Assessment Questionnaire-Disability Index (HAQ-DI <0.5) remission. Among 129 patients whose mTSS progression was evaluated at month 12, 83 (64.3%) achieved structural remission (ΔmTSS ≤0.5 for 12 months). SDAI remission at month 6 was identified as a significant predictor of both functional (OR, 3.732; 95% CI, 1.328–10.489) and structural remissions (OR, 4.301; 95% CI, 1.298–14.243) at month 12 after adjusting for covariates. Conclusions: Aiming for SDAI remission at month 6 is an appropriate strategy to obtain good functional and structural outcomes at month 12.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Objectives Interleukin-6 (IL-6) is implicated in rheumatoid arthritis (RA) pathophysiology. Unlike IL-6 receptor inhibitors, sirukumab is a human monoclonal antibody that selectively binds to the IL-6 cytokine. The phase III, multicentre, randomised, double-blind, placebo-controlled, parallel-group SIRROUND-D study (ClinicalTrials.gov identifier NCT01604343) evaluated the efficacy and safety of sirukumab in patients with active RA refractory to disease-modifying antirheumatic drugs. Methods Patients were randomised 1:1:1 to treatment with sirukumab 100 mg every 2 weeks, 50 mg every 4 weeks or placebo every 2 weeks subcutaneously. Results through week 52 are reported. Results Of 1670 randomised patients, significantly more patients achieved American College of Rheumatology 20% (ACR20) response at week 16 (coprimary endpoint) with sirukumab 100 mg every 2 weeks (53.5%) or 50 mg every 4 weeks (54.8%) versus placebo (26.4%; both p<0.001). Mean (SD) change from baseline in modified Sharp/van der Heijde score at week 52 (coprimary endpoint) was significantly lower with sirukumab (100 mg every 2 weeks: 0.46 (3.26); 50 mg every 4 weeks: 0.50 (2.96)) versus placebo (3.69 (9.25); both p<0.001). All major secondary endpoints (week 24 Health Assessment Questionnaire-Disability Index change from baseline, ACR50 response, 28-joint Disease Activity Score based on C reactive protein and major clinical response (ACR70 for six continuous months by week 52)) were met. The most common adverse events with sirukumab were elevated liver enzymes, upper respiratory tract infection, injection site erythema and nasopharyngitis. Conclusions Sirukumab 100 mg every 2 weeks and 50 mg every 4 weeks led to significant reductions in RA symptoms, inhibition of structural damage progression and physical function and quality of life improvements, with an expected safety profile. Trial registration number NCT01604343; Results.

© 2017 Japan College of Rheumatology. Objective: We seek to evaluate the opinions of nurses and doctors in Japan regarding EULAR recommendations for nurses’ roles in the management of chronic inflammatory arthritis. Methods: This is a cross-sectional survey within Japan. We randomly selected nurses and doctors engaged in consultation of patients with rheumatoid arthritis (RA) and assessed their agreement and opinions on the feasibility of implementing EULAR recommendations, including potential barriers. Results: 431 nurses and 128 doctors completed the questionnaire. For both nurses and doctors, levels of feasibility showed statistically significant lower results compared with those of agreement for all items. When compared between nurses and doctors, agreement showed no statistically significant differences, while nurses’ answers were statistically significant lower for feasibility. Insufficient time, staff and knowledge, lack of established procedures and facilities, and lack of an education system for nurses were cited as barriers to the feasibility of implementing EULAR recommendations. Conclusions: This is the first survey within Japan evaluating opinions regarding EULAR recommendations for nurses’ roles. We found that while agreement was high, feasibility was generally believed to be low. We recommend further research and collaboration between medical professionals in order to implement these recommendations in Japan.

© 2017, Govi-Verlag Pharmazeutischer Verlag GmbH. All rights reserved. In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enrolled a total of 10 Japanese adult patients with RA who were treated with infliximab concomitantly with methotrexate or azathioprine. Serum concentrations of infliximab and ATI of these patients were measured. The mean serum infliximab concentrations was 1.6±1.3 μg/ml in patients with methotrexate and 1.0±0.5 μg/ml in patients with azathioprine. Serum ATI concentrations were below the limit of quantitation in 4 of 5 patients in each group. The results from the present study suggest that azathioprine suppresses ATI production.

© 2015 Elsevier Ltd. Objectives: To conduct a comprehensive quantitative proteomics analysis of novel serum protein biomarkers based on synovitis status associated with matrix metalloproteinase-3 (MMP-3) and to determine the clinical significance of these biomarkers in rheumatoid arthritis (RA). Methods: Patients with untreated RA (n=28), primary Sjogren's syndrome (pSS) (n=30), and healthy controls (HCs) (n=30) were enrolled for the screening assay. A total of 1128 serum proteins were analyzed using the SOMAscan™ assay. Serum levels of MMP-3 and interleukin (IL)-16 were measured using a latex turbidimetric immunoassay and ELISA at baseline and 12 weeks after treatment with methotrexate (MTX) for MTX-naïve RA patients (n=28) or with the biologics tocilizumab (TCZ) (n= 7), abatacept (ABT) (n=11) or infliximab (n=22) for MTX-inadequate response (IR) RA patients. Correlation analysis was conducted using Spearman's rank correlation method. Results: Proteomics showed that serum IL-16 levels were most positively correlated with those of MMP-3 (ρ= 0.51, p< 0.01) and were significantly increased in patients with untreated active RA compared to HCs (p< 0.01) or those with pSS (p< 0.01). IL-16 levels decreased following treatment in both the MTX-naïve and MTX-IR groups. Regarding clinical response, fluctuations in IL-16 levels were positively associated with changes in clinical indicators, particularly the Clinical Disease Activity Index (ρ= 0.89, p< 0.01) in the TCZ and ABT-treated group. However, no similar correlation was noted in MMP-3 and acute phase reactants in any groups. Conclusions: IL-16 was a more effective clinical parameter than MMP-3, C-reactive protein, or erythrocyte sedimentation rate in both MTX-naive and MTX-IR RA patients. IL-16 might be a useful biomarker for evaluating clinical response in RA patients.