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Objectives: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis. Methods: We retrospectively assessed patients with antibody-associated vasculitis who received IVCY every 2–3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5–12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes was also evaluated. Results: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94–19.8) for VLD and 5.1 (95% CI 1.21–21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly. Conclusion: Low-dose IVCY (7.5–12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg). [ABSTRACT FROM AUTHOR]

Objectives: Our previous study showed that the effectiveness of tumor necrosis factor (TNF) inhibitors was attenuated in anti-human T-cell leukemia virus type 1 (HTLV-1) antibody-positive patients with rheumatoid arthritis (RA). We aimed to evaluate the effectiveness and safety of non-TNF inhibitors in anti-HTLV-1 antibody-positive patients with RA. Methods: We reviewed patients with RA who received abatacept or tocilizumab as the first biologic agent. We used the data of patients treated with TNF inhibitors from our previous study to compare the effectiveness between the anti-HTLV-1 antibody-positive patients treated with TNF inhibitors and non-TNF inhibitors using the inverse probability of treatment weights (IPTW) method. Results: A total of 359 patients were divided into anti-HTLV-1 antibody-negative and -positive patients of 332 and 27, respectively. No statistically significant difference was observed in the change in the clinical disease activity index between the anti-HTLV-1 antibody-positive and -negative patients. The results using the IPTW method showed a significant association between the non-TNF inhibitors treatment and a better response. None of the patients developed adult T-cell leukemia/lymphoma or HTLV-1-associated myelopathy/tropical spastic paraparesis during the 24 weeks. Conclusion: Our results indicate that non-TNF inhibitors treatment is safety, and the effectiveness is not attenuated also in anti-HTLV-1 antibody-positive patients. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether specific parameters contribute to clinical outcomes at 1 year post-diagnosis in early rheumatoid arthritis (RA) patients under the 'treat-to-target' strategy in clinical practice. Methods: We retrospectively analyzed 125 RA patients selected according to the following criteria; the patients' symptom duration was ≤6 months, and none had experience with DMARDs. We evaluated the patients' clinical disease activity at baseline and 1 year of treatment and the musculoskeletal ultrasound (MSUS)-detected synovitis activity at baseline. We performed an analysis to identify parameters that contribute to SDAI remission and the use of biologic/targeted synthetic (b/ts) DMARDs at 1 year post-diagnosis. Results: Forty-seven patients received b/tsDMARDs therapy, and 58 patients achieved SDAI remission at 1 year post-diagnosis. Rheumatoid factor positivity, low patient's/evaluator's global assessment at baseline, and methotrexate use at 1 year post-diagnosis were associated with SDAI remission. The baseline clinical disease activity and MSUS scores were not associated with SDAI remission. Anti-cyclic citrullinated peptide antibody positivity/high titer and high swollen joint counts or the presence of severe synovial hypertrophy at baseline were associated with the use of b/tsDMARDs therapy. Conclusion: The value of the expected poor-prognosis factors may be diminished by intensive therapy within the 'windows of opportunity'. [ABSTRACT FROM AUTHOR]

Objectives: To investigate predictors of inadequate response to first conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including methotrexate (MTX) in untreated rheumatoid arthritis (RA) patients in daily clinical practice. Methods: Inadequate response to MTX or other csDMARDs was defined as being not low disease activity at 12 months in more than 3 of 4 composite measures, and discontinuation or start of biologic DMARDs. The association between baseline factors and csDMARDs-IR was assessed by univariate and multivariate logistic regression analyses. Results: Four hundred and eleven and 146 patients were started on MTX and other csDMARDs, respectively; 218 patients were responsive to MTX, with a response rate of 47.0%. Tender joint count (TJC, 6 in 28joints, odds ratio [OR]=1.67, 95% confidence interval [CI] 1.06-2.64) and CRP (1.0mg/ dL, OR = 1.72, 95%CI: 1.10-2.70) at baseline were identified as predictors on multivariate logistic regression analysis. TJC (OR = 3.60, 95%CI: 1.29-10.00) was the factor identified as a predictor of the development of other csDMARDs-IR. Conclusion: In this observational study, patients with untreated RA at risk of inadequate response to MTX included those with a higher TJC and higher CRP, while a higher TJC was the only independent predictor of an inadequate response to csDMARDs other than MTX. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to evaluate the efficacy and safety of bortezomib for treating systemic lupus erythematosus (SLE), in patients whose disease activity could not be controlled. Methods: Fourteen SLE patients with persistent disease activity were selected, who required prednisolone doses of >10 mg/d despite concomitant immunosuppressive therapy. Patients were randomly administered either bortezomib or a placebo, eight times. The primary and secondary end-points were a change in anti-dsDNA antibody titer at week 24 and the SLE Responder Index (SRI), respectively. Results: In the bortezomib group, four out of eight patients discontinued the trial; three others failed to complete the minimum protocol treatment due to adverse reactions. The changes in anti-dsDNA antibody titers at week 24 were 4.24% and -1.96%, for the bortezomib and placebo groups, respectively, disconfirming bortezomib's efficacy. In contrast, the corresponding SRI at week 12 was 75% and 40%. Conclusions: As bortezomib therapy for SLE is associated with many adverse reactions, treatment indications should be selected carefully, and protocols should aim to prevent these occurrences. Although the change in anti-dsDNA antibody titer did not support the efficacy of bortezomib as a treatment for SLE, high SRI in the treatment group suggests bortezomib may utilize mechanisms other than inhibition of anti-dsDNA antibody production. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of the 2012 Systemic Lupus International Collaborating Clinics criteria (SLICC-12) on classifying systemic lupus erythematosus (SLE) in an uncontrolled multi-centered study with real-life scenario of the patients in Japan. Methods: This study comprised 495 patients with SLE or non-SLE rheumatic diseases and allied conditions from 12 institutes in Japan. Chart review of each patient was performed by the 27 expert rheumatologists and diagnosis of 487 cases reached to the consensus. Value of the SLICC-12 on SLE classification was analyzed comparing with the 1997 revised American College of Rheumatology SLE classification criteria (ACR-97) employing the expert-consented diagnoses. Results: Compared to the ACR-97, the SLICC-12 had a higher sensitivity (ACR-97 vs. SLICC-12: 0.88 vs. 0.99, p<.01) and comparable specificity (0.85 vs. 0.80). The rate of misclassification (0.14 vs. 0.11) or the area under the receiver operating characteristic curves (0.863 vs. 0.894) was not statistically different. In the cases that diagnoses corresponded in high rates among experts, both criteria showed high accordance of SLE classification over 85% with the expert diagnoses. Conclusion: Although employment of SLICC-12 for the classification for SLE should be carefully considered, the SLICC-12 showed the higher sensitivity on classifying SLE in Japanese population. [ABSTRACT FROM AUTHOR]

Objective: To examine whether magnetic resonance imaging (MRI) findings at baseline predict radiographic progression in early-stage rheumatoid arthritis (RA) patients who have achieved sustained good clinical response. Methods: This is a sub-analysis from the one-year observational study of Nagasaki University Early Arthritis Cohort. Definition of 'good clinical response' was a decrement of disease activity score (DAS) 28-1.2 at three months with achievement of DAS28 remission through 6-12 months. Gd-enhanced MRI of both wrists and finger joints were examined at baseline and scored using rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Annual increment of Genant-modified Sharp score (GSS)>0 was defined as 'radiographic progression'. Predictors of radiographic progression were determined by logistic regression analysis. Results: Twenty-four subjects were selected in the present study. Each median RAMRIS synovitis, bone edema, bone erosion, and GSS at baseline were 6.5, 0.5, 0, and 0, respectively. Five patients developed radiographic progression at one year. Multivariate logistic regression analysis has shown that RAMRIS bone erosion at baseline is the only independent predictor of radiographic progression at one year (p=.032). Conclusions: Our data suggest that MRI bone erosion predicts poor radiographic outcome of earlystage RA even if it has been successfully treated. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence of ultrasonographic abnormalities of sternoclavicular joints (SCJ) and peripheral joints (PJ) in patients with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome. Methods: Thirteen patients with SAPHO syndrome who fulfilled diagnostic criteria proposed by Kahn for SAPHO syndrome 2003 and 13 healthy individuals age- and sex-matched were enrolled. Synovitis, defined by synovial hypertrophy with power Doppler (PD) signals, of the SCJ and the PJ including wrist, MCP, PIP, and the other symptomatic joints were evaluated by ultrasound (US). Results: Synovitis with PD signals was detected in 16 (61.5%) of the 26 SCJ and 11 (84.6%) of the SAPHO syndrome patients, and none of the controls. Synovitis with PD signals in any PJ was detected in 4 (30.7%) of the SAPHO syndrome patients. Conclusions: Synovitis of the SCJ and PJ in SAPHO syndrome was detectable by US with a PD method. US can be useful for the diagnosis of SAPHO syndrome. [ABSTRACT FROM AUTHOR]

Objectives: Autonomic dysfunction is closely associated with autoimmune diseases (AID) including primary biliary cirrhosis (PBC). The objective of this study was to determine the prevalence of anti-ganglionic (nicotinic) acetylcholine receptor (gAChR) antibodies in patients with AID. Methods: We determined the presence of gAChR antibodies in serum samples from 146 patients (systemic lupus erythematosus [SLE]=32; rheumatoid arthritis [RA]=43; systemic sclerosis [SSc]=38; PBC=33) without information regarding autonomic symptoms, as well as 34 patients with other neurological diseases (OND), and 73 healthy controls (HC). We specifically analyzed sera for anti-gAChRa3 and -b4 antibodies using the luciferase immunoprecipitation system (LIPS) assay. Results: LIPS assay detected anti-gAChRa3 and -b4 antibodies in the sera from patients with SLE (12.5%, 4/32), RA (18.6%, 8/43), SSc (13.2%, 5/38), PBC (9.1%, 3/33), OND (2.9%, 1/34), and HC (0.0%, 0/73). There were no significant correlations between the levels of anti-gAChRa3 and -b4 antibodies, and the total titers of autoantibodies in AID. Conclusions: The results demonstrated a significant prevalence of anti-gAChR antibodies in patients with AID, which is independent of the production of other autoantibodies in patients with autoimmune diseases. These anti-gAChR antibodies could mediate the autonomic dysfunction involved in the autoimmune mechanisms of AID. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the association between hand dysfunction and ultrasound (US)- detected articular synovitis and tenosynovitis in patients with rheumatoid arthritis (RA). Methods: Thirty RA patients were examined. In both hands of all subjects, articular synovitis and tenosynovitis were assessed by US at 22 joints and 12 tendons. Each joint and tendon was scored by gray-scale (GS) and power Doppler (PD) on a scale from 0 to 3. The sums of the GS or PD scores were used as the articular synovitis score and the tenosynovitis score. The sum of the articular synovitis and tenosynovitis scores was used as the combined US score. Hand dysfunction was evaluated by a grip-Health Assessment Questionnaire (HAQ) and visual analog scale of morning stiffness (MS-VAS). We used Spearman's correlation coefficient to determine the relationships among the US scores, the two hand dysfunction indices, and the DAS28-ESR. Results: The articular synovitis scores were significantly correlated with grip-HAQ (GS: rs = 0.47, p = 0.009, PD: rs = 0.48, p = 0.006), but not with MS-VAS. The tenosynovitis scores were correlated with MS-VAS (GS: rs = 0.38, p = 0.039, PD: rs = 0.36, p = 0.053), but not with grip- HAQ. Both grip-HAQ (GS: rs = 0.53, p = 0.002, PD: rs = 0.55, p = 0.001) and the MS-VAS (GS: rs = 0.39, p = 0.031, PD: rs = 0.47, p = 0.008) were correlated with the combined US scores. Conclusions: The US scores combined with articular synovitis and tenosynovitis scores well reflect the severity of hand dysfunction in early-stage RA patients. [ABSTRACT FROM AUTHOR]

Objective: We evaluated whether the early responsiveness of ultrasound synovitis can predict the clinical response in rheumatoid arthritis (RA) patients treated with biologic diseasemodifying anti-rheumatic drugs (bDMARDs). Methods: Articular synovitis was assessed by ultrasound at 22 bilateral wrist and finger joints in 39 RA patients treated with bDMARDs. Each joint was assigned a gray-scale (GS) and power Doppler (PD) score from 0 to 3, and the sum of the GS or PD scores was considered to represent the ultrasound disease activity. We investigated the correlation of the change in ultrasound disease activity at three months with the EULAR response criteria at six months. Results: GS and PD scores were significantly decreased at three months (p50.0001). The % changes of the GS and PD scores at three months were significantly higher at six months in moderate and good responders compared with non-responders (p50.05). These tendencies were numerically more prominent if clinical response was set as good responder or Disease Activity Score 28 remission. Poor improvement of ultrasound synovitis scores had good predictive value for non-responders at six months. Conclusions: The responsiveness of ultrasound disease activity is considered to predict further clinical response in RA patients treated with bDMARDs. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of switching the route from intravenous tocilizumab (TCZ) infusion (TCZ-IV) to subcutaneous TCZ injection (TCZ-SC) in a real-world setting through a comparison of the clinical response. Methods: Fifty-eight rheumatoid arthritis (RA) patients, for whom TCZ-SC was initiated following TCZ-IV between June 2013 and August 2014, were consecutively enrolled. Disease activity score (DAS)28-ESR, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were examined at baseline and after switching from TCZ-IV to TCZ-SC for 3 months. We investigated whether body weight and body mass index (BMI) affected the efficacy of TCZ-SC. Results: Most of the patients had achieved remission or low disease activity at baseline (77.6% examined by DAS28). Fifty-seven patients (98%) continued the TCZ-SC treatment, and the disease activity was well controlled after 3 months. DDAS28 tended to be worsened after switching to TCZ-SC in the high-body-weight groups (-60 kg) as compared with the groups with body weight560 kg, although no statistical significance was found. BMI did not affect the efficacy of TCZ-SC. Conclusions: Caution should be exercised in the high-body-weight subjects, but these data indicate that TCZ-SC maintains the favorable RA disease activity established using TCZ-IV. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to identify variables at diagnosis to predict the subsequent relapse in patients with Takayasu arteritis (TA). Methods: We retrospectively analyzed 33 patients with TA in our hospitals from April 2000 to July 2015. We collected baseline variables at diagnosis including clinical symptoms and laboratory data using medical records and investigated associations of these indices with subsequent relapses. Results: The patients included two males and 31 females (94%). The median age at diagnosis was 39 years old, and the median follow-up duration was 90 months. Relapse was noted in 18 patients (55%). Only lower total cholesterol (Tcho) [median, 117 mg/dL (relapse) vs. 182 mg/dL (nonrelapse)] was preferentially distributed in the relapse group as compared with the nonrelapse group. Multivariable logistic analysis showed that hypocholesterolemia (5150 mg/dL) at diagnosis was the only predictor of subsequent relapse (odds ratio: 5.43, 95% confidence interval: 1.13-30.19; p=0.035). The nonrelapse survival rate was significantly lower in the group with a Tcho level5150 mg/dL by Kaplan-Meier estimate (p50.001). Conclusions: We found that hypocholesterolemia at diagnosis is a predictor of subsequent relapse in patients with TA. [ABSTRACT FROM AUTHOR]

Efficacy of tocilizumab in active early-stage RA patients despite methotrexate was evaluated for 12 months. One out of 5 patients was quitted by infusion reaction whereas tocilizumab continued for 12 months in the remaining 4 patients. Power Doppler articular synovitis was reduced in every patient and disappeared in 2 patients. Marked MRI osteitis, found in 1 patient, had disappeared at 12 months. Present results confirm the efficacy of tocilizumab by ultrasonography and MRI. [ABSTRACT FROM AUTHOR]

Objective. To explore the clinical application of automated scanning of wrist and finger joints by an Automated Breast Volume Scanner (ABVS) in patients with rheumatoid arthritis (RA). Methods. A total of 140 metacarpophalangeal (MCP) joints and 28 wrist joints from the 14 active RA patients were examined by both an ABVS system (the ACUSON S2000) from dorsal sites and by conventional ultrasonography (US) from multiple directions on the same day. We used a semiquantitative scale from 0 to 3 of synovial hypertrophy and the presence of bone erosion by grayscale for both methods; the efficacy of the two methods for identifying synovial hypertrophy and bone erosion were evaluated by kappa coefficient. Results. The scanning time of the ABVS was 2 min per patient and that of conventional US was 15 min per patient. The kappa coefficients of synovial hypertrophy in the MCP joints were 0.60 and 0.79 in wrist joints. These values were increased in the joints where synovial hypertrophy was moderate to severe (scores greater than 2). The kappa coefficients for the presence of bone erosion in the MCP joints were 0.74 and 0.93 in wrist joints. Conclusion. The present data showed a substantial agreement between ABVS and conventional US for assessments of the synovial hypertrophy and bone erosion of wrist and finger joints in patients with RA. Since ABVS can scan the wrist and finger joints automatically in a short time, ABVS is a helpful new ultrasonic method to examine joint injuries in patients with RA. [ABSTRACT FROM AUTHOR]

Objectives. IgG4-related disease (IgG4-RD) is characterized by various serological abnormalities. Some patients with IgG4-RD present with hypergammaglobulinemia, hypocomplementemia, and autoantibodies recognizing rheumatoid factors and nuclear factors. However, whether IgG4-RD is an autoimmune disease remains unclear. Methods. Here, we used immune complexome analysis to comprehensively identify constituent antigens of circulating immune complexes isolated from 10 patients with IgG4-related dacryoadenitis and/or sialadenitis (IgG4-RDS) which is one condition associated with IgG4-RD. Results. We detected each of 125 distinct antigens in independent samples from two or more patients with IgG4-RDS. Of them, 17 antigens were found to be specific to patients with IgG4- RDS by comparing 125 antigens with all the antigens found in other connective tissue diseases (antineutrophil cytoplasmic antibody-associated vasculitis, Takayasu's arteritis, mixed connective tissue disease, dermatomyositis, Sjögren's syndrome, systemic scleroderma, and systemic lupus erythematosus) or healthy donors. The number of disease-specific antigens associated with IgG4-RDS was comparable to those autoimmune diseases. Conclusions. Studies of the 17 IgG4-RDS-specific antigens might lead to a better understanding of the pathogenesis of IgG4-RD, but further study of the prevalence of these CIC-associated antigens that involves a selective and sensitive assay will be needed to determine their potential as diagnostic or pathogenic biomarkers. [ABSTRACT FROM AUTHOR]