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Rheumatoid arthritis (RA) is a systemic inflammatory disease in which the predominant symptom is polyarthritis that follows a chronic and progressive clinical course characterized by destructive synovitis and various immune disorders. Striking progress in RA treatment was achieved with the emergence of monoclonal antibodies to target cytokines. However, drug choices are limited for many patients due to resistance to multidrug antirheumatic therapy, concomitant disease, and infection. We evaluated the efficacy of treatment in 85 patients with RA for whom leukocytapheresis (LCAP) was initiated at our hospital between 2006 and 2015. All patients continued drug therapy and were treated with LCAP once a week for up to 5 weeks. The clinical response was evaluated at the completion of LCAP series and 4 weeks later using the American College of Rheumatology (ACR) criteria and the 28-joint disease activity score (DAS28) of European League Against Rheumatism (EULAR). The tender joint counts, swollen joint counts, and C-reactive protein (CRP) levels decreased remarkably. DAS28-CRP was significantly improved by LCAP. And furthermore, the efficacy lasted at least 4 weeks after the completion of LCAP. These results suggest that LCAP is a beneficial and are consistent with several trials' reported effect of LCAP. This treatment can contribute to improvements in activities of daily living (ADLs) and long-term outcome by improving swollen and tender joint counts and CRP levels even in refractory patients for whom the use of conventional disease-modifying antirheumatic drugs (DMARDs) and biopharmaceuticals is problematic. LCAP might be a promise therapy to refractory RA.

Background Japan is the world’s most aged country. The number of patients with polymyalgia rheumatica (PMR) is expected to increase more. Classification criteria including ultrasound findings were published in 2012, but the ability to differentiate PMR from rheumatoid arthritis (RA) was not significant. We will clarify whether recently reported ultrasound findings (1, 2) which could be characteristic in PMR are helpful for distinguishing from other diseases and treatment outcome in suspected PMR patients. Objectives Patients who were clinically suspected of PMR and underwent ultrasound examination from March 2015 to July 2018. Methods Recorded ultrasound images were retrospectively interpreted by the ultrasound expert, who was blind for clinical information. They were classified into three groups of PMR, RA, others/no inflammation. Initial dose of glucocorticoid (GC), therapeutic response, presence or absence of relapse, and concomitant medications were collected and compared among the 3 groups. Cases in which steroids had already been used before ultrasound examination were excluded from the analysis. Results The number of subjects was 81, and the number of ultrasound examination was 88. The ultrasound expert classified 29 PMR, 20 RA, 3 other/no inflammation. 18.5% (15/81) of the subjects were improved with no GC and relapse. The average prednisolone (PSL) dose was 15.3 mg in the PMR group, and 9.7 mg in the RA group. Concomitant medications were introduced in 31% (9/29) of PMR group, in 65% (13/20) of RA group. Conclusion Ultrasound is useful for distinguishing PMR from seronegative RA and other arthralgia. These findings showed that ultrasound is useful for the proper use of GC and concomitant medications. References [1] Suzuki T, Yoshida R, Hidaka Y, Seri Y. Proliferative Synovitis of the Shoulder Bursae is a Key Feature for Discriminating Elderly Onset Rheumatoid Arthritis Mimicking Polymyalgia Rheumatica From Polymyalgia Rheumatica. Clin Med Insights Arthritis Musculoskelet Disord 2017;10: 1179544117745851. [2] Suzuki T, Yoshida R, Okamoto A, Seri Y. Semiquantitative Evaluation of Extrasynovial Soft Tissue Inflammation in the Shoulders of Patients with Polymyalgia Rheumatica and Elderly-Onset Rheumatoid Arthritis by Power Doppler Ultrasound. Biomed Res Int 2017;2017: 4272560. Disclosure of Interests Tomohiro Kawaguchi: None declared, Michihiro Ogasawara: None declared, Ken Yamaji: None declared, Naoto Tamura Grant/research support from: Astellas Pharma Inc., Asahi Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. LTD, Eisai Inc., :Takeda Pharmaceutical Company Ltd., Speakers bureau: Janssen Pharmaceutical K.K., Bristol-Myers Squibb K.K., :Mitsubishi Tanabe Pharma Co.

Background In the EULAR recommendation on rheumatoid arthritis (RA) treatment, short-term steroid combination should be considered at the start of DMARDs treatment. In this study, we analyzed the present condition of steroid combined use in Japan and the actual situation of side effects in recent years. Objectives RA patients who started treatment with DMARDs at our hospital during July 2008 to April 2018, Methods A new incidence of hypertension (HTN), diabetes (DIB), dyslipidemia (HLP), infection (INF) were compared between the two groups of steroid combined use group (D_PSL) and noncombined group (D_nonPSL) and analyzed by Cox regression analysis. The cases had there complications before the start of RA treatment were excluded from the analysis. Results The number of cases of analysis was 573 (D_PSL = 216, D_nonPSL = 357, average observation period: 5.22±2.70 year), and the new incidence of each complication was INF 50/561 (D_PSL 16.2%vs. D_nonPSL 4.56%[16/351], p=0.000094), HTN 48/527 cases (13.3%[25/188] vs.6.78%[23/339], P = 0.0148), DIB 24/558 (6.16%[13/211] vs. 3.17%[11/347], p = 0.136), HLP 72/542 (15.8%[32/202] vs. 11.8%[40/340], p = 0.198). The incidence of INF was high in D_PSL group in both groups over 65 and under 65 years old (p = 0.00658, p = 0.00267), HTN was high in D_PSL group only in group over 65 years old (p=0.0276, p=0.0554). Average starting amount of steroids was 6.07±10.2 mg, cases of non-withdrawal of steroid at 1, 2, 3 years later is 79.7%, 72.2% and 66.3% respectively. Conclusion Combined use of steroid at the start of DMARDs increased the rate of mortality of infection requiring hospitalization and hypertension. More than half of them were difficult cases of withdrawal of steroids. From the viewpoint of side effect, it is necessary to study the optimization of steroid therapy in the future. Disclosure of Interests Michihiro Ogasawara: None declared, Yosuke Shimada: None declared, Yoshiyuki Abe: None declared, Ken Yamaji: None declared, Satoshi Hori: None declared, Naoto Tamura Grant/research support from: Astellas Pharma Inc., Asahi Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. LTD, Eisai Inc., :Takeda Pharmaceutical Company Ltd., Speakers bureau: Janssen Pharmaceutical K.K., Bristol-Myers Squibb K.K., :Mitsubishi Tanabe Pharma Co.

Objectives: To determine which grade of ultrasound (US) synovitis corresponds to clinically involved joints in rheumatoid arthritis (RA) and develops a new US-adjusted composite measure. Methods: Clinical and US examinations were performed on 137 patients with RA (28 joints). Synovial effusion, hypertrophy, and blood flow were semiquantitatively graded from 0 to 3 using gray scale (GS) and power Doppler (PD) modes. We calculated US-adjusted simple disease activity index (SDAI) and assessed feasibility, and external validity by comparing with erythrocyte sedimentation rate (ESR), and modified health assessment questionnaires (MHAQ). Results: GS ≥2 and PD ≥0 corresponds to clinically swollen joints, and GS ≥2 and PD ≥1 corresponds to tender joints. The US-adjusted SDAI showed the highest correlation when US-determined swollen joints were defined as PD ≥2 with ESR, and GS ≥3 and PD ≥2 with MHAQ. A feasible US-adjusted SDAI examining only clinically involved joints still showed a higher correlation with ESR and MHAQ than SDAI. Conclusion: Our composite measure complemented by US only for clinically involved joints is feasible and reliable for monitoring disease activity.

Objectives This study aims to analyze the distribution and clinicopathological characteristics of anti-aminoacyl-transfer ribonucleic acid (tRNA) synthetase (ARS) antibodies in rheumatoid arthritis patients. Patients and methods We retrospectively studied the anti-ARS antibody levels in 228 RA patients' (44 males, 184 females; mean age 62.9±14.0 years; range 23 to 88 years) sera from their medical charts. We determined the association with anti-cyclic citrullinated peptide antibody levels, interstitial lung disease (ILD), rheumatoid factor, and methotrexate or biological disease modifying antirheumatic drug treatments. Results Anti-ARS antibodies were detected in 14 RA patients (6.1%). ILD complications were significantly higher among anti-ARS antibody-positive patients (57.1% vs 22.4%, p

We evaluated the bradykinin generation level during leukocytapheresis (LCAP) using novel CellsorbaTM CS-180S, which has sodium pyrosulfite and sodium carbonate as a filling solution. Subjects of this study were 14 rheumatoid arthritis patients. Regardless of the type of anticoagulant used, bradykinin levels were lower with the novel CS-180S than with the conventional CS-180S (28.7 ± 53.3 vs. 8.0 ± 2.7 as the mean ± standard deviation). When anticoagulants other than nafamostat mesilate were used with the conventional CS-180S, bradykinin levels increased at the column outlet compared with the column inlet, and adverse effects of bradykinin were seen in several cases. In contrast, bradykinin levels remained low and no bradykinin-associated adverse events were observed with the novel CS-180S. We recommend using the novel column instead of the conventional column in the treatment of LCAP. J. Clin. Apheresis 29:90–96, 2014. © 2013 Wiley Periodicals, Inc.

Leukocytapheresis (LCAP) is a safe, unique therapy pertaining to intractable rheumatoid arthritis (RA) even in cases of drug allergy or infectious states. To investigate how to represent LCAP efficacy, we have conducted gene expression analyses from the peripheral blood of RA patients treated with non-woven polyethylene terephthalate filters. Peripheral blood samples were collected immediately before and after treatment from eight RA patients who received LCAP. Among these patients, all of them achieved 20% improvement in the core set of the American College of Rheumatology (ACR20), and thus, they were confirmed as LCAP responders. Gene expression analysis was done with a high-resolution DNA microarray. The results of each of the two groups' gene expression values (immediately before and after LCAP) were calculated using Welch's t-test. Calculations were performed with a statistical software R.basic package: if the P-value was less than 0.05, this was seen as a significant change. In a comparison of 25,370 gene expressions, the number of genes showing a P-value < 0.05 in the upregulating group was 2110, and in the downregulating group it was 1864. The results of pathway analysis using the MetaCore program indicate that gene groups work for cytoskeletal remodeling are upregulated, and genes related to immune responses, such as antigens presenting via major histocompatibility complex class I and II, are downregulated just after LCAP. These findings may relate to LCAP efficacy for RA patients, but this needs further investigation.

A 71-year-old woman was diagnosed with rheumatoid arthritis in 2002. Treatment was started with methotrexate and she was switched to adalimumab in 2006. In May 2008, she started complaining of swelling of the left axilla and the left elbow lymph nodes, and adalimumab was discontinued in December. Her lymphadenopathy did not resolve and she was admitted to hospital with fever in May 2009. Subsequent laboratory examinations showed that serum alkaline phosphatase, gamma-glutamyl transpeptidase, C-reactive protein, and soluble interleukin-2 receptor levels were 3,078 IU/l, 510 IU/l, 20 mg/dl, and 7,290 U/ml, respectively. Gallium scintigraphy showed high-intensity areas in the above-mentioned lymph nodes. She suddenly progressed to jaundice and died of pulmonary edema on the 25th day of hospitalization. Autopsy indicated large atypical cells with a distorted nucleus that had multiplied in the above-mentioned lymph nodes. On immunohistochemical staining these cells showed positive staining for CD15, CD30, PAX-5, Epstein-Barr virus (EBV) early small RNA (EBER), and LMP-1. Reactivation of EBV was diagnosed via EBV antibodies and an EBV DNA determination. We considered that she had developed EBV-associated lymphoproliferative disorders due to immunodeficiency caused by adalimumab administration. Reactivation of EBV associated with adalimumab and the relationship of this reactivation to malignant lymphoma have been rarely reported.

We conducted a study to evaluate the effect of various anticoagulant agents on large-volume leukocytapheresis using the new Cellsorba CS-180S Filter filled with a changed solution of sodium pyrosulfite and sodium carbonate. We conducted the study on a total of 12 cases of rheumatoid arthritis. As the anticoagulant agents we used sodium citrate, nafamostat mesilate and low molecular weight heparin. The new Cellsorba CS-180S was safely used with the various blood anticoagulant agents. Also, through adjustment of the sodium citrate percentage to the blood flow volume, it is hypothesized that it is possible to increase the neutrophil removal rate.

To retrospectively evaluate the efficacy and safety of combination therapy with tacrolimus (TAC) and other disease-modifying antirheumatic drugs (DMARDs). One hundred fifteen rheumatoid arthritis (RA) patients treated with tacrolimus were enrolled in this retrospective analysis. We collected clinical information, including patient background, treatment efficacy (evaluated using the DAS score), and adverse events observed. Multiple logistic regression analysis was conducted to analyze factors contributing to clinical response and adverse effects. The disease activity score of 28 joints (DAS28) improved significantly at 24 weeks, and continuation rate at 1 year was 57.9%. There was no difference in continuation rate between different DMARD combinations, and not only methotrexate (MTX) but also bucillamine (BUC) and salazosulfapyridine (SSZ) were effective combination partners with TAC. No serious adverse events were observed, and no different inefficacy or safety was observed between non-elderly (

Objective. To determine the degree of contribution and the contributing factors of ultrasound in the diagnosis of rheumatoid arthritis (RA) in daily clinical practice and the predictive differences depending on seropositivity. Methods. We included 122 patients who presented with the main complaint of finger and/or wrist joint pain but for whom no definite diagnosis was reached or treatment strategy was provided. Ultrasound was performed on at least 22 joints (both wrist joints, proximal interphalangeal joint, and metacarpophalangeal joints), and patients were followed for ≥6 months. Factors contributing to RA diagnosis were determined and compared between seropositive and seronegative RA patients. Results. RA was diagnosed in 52 of 122 patients, in whom the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria (odds ratio [OR] = 4.74, P = 0.01) and gray scale (GS) grade of 3 (OR = 3.64, P = 0.04) for ≥ 1 joint were the contributing factors. In seropositive RA, the ACR/EULAR criteria (OR = 15.53, P < 0.001) and power Doppler (PD) ≥ 2 for ≥ 1 joint (OR = 10.48, P = 0.0048) were the contributing factors. In seronegative RA, PD ≥ 1 for ≥ 1 joint contributed the most (OR = 20.00, P = 0.0044), but the ACR/EULAR criteria did not contribute to RA diagnosis (P = 0.57). Conclusion. Ultrasound findings contributed to RA diagnosis in clinical practice. The contributing factors are different in the presence or absence of seropositivity, and ultrasound complementation was particularly useful in seronegative RA patients.

Treatment for rheumatoid arthritis (RA) should aim to achieve full remission. The aim of this study was to investigate predictors of persistent subclinical synovitis and whether longer clinical remission is effective in reducing subclinical synovitis.Forty-four RA patients who achieved DAS28ESR clinical remission for at least 3 months were enrolled in this study and underwent ultrasound examination of 22 joints (bilateral proximal interphalangeal joints, metacarpophalangeal joints, and wrists); bilateral hand X-ray; and blood examination. The severity of synovial effusion, synovial hypertrophy, and blood flow were semi-quantitatively graded from 0 to 3 using gray-scale (GS) and power Doppler (PD) modes.Among patients with DAS28ESR-defined clinical remission, 59.1% (26/44) demonstrated residual synovitis (≥ PD1) in at least one joint. Genant-modified total Sharp score (TSS) demonstrated the highest statistical difference between patients with and without residual subclinical synovitis (p = 0.0057), and full remission was only observed in patients with low TSS. A nonsignificant trend for decreased residual synovitis with longer sustained clinical remission was also observed (p = 0.724).Residual synovitis can persist during clinical remission, particularly in patients with progressive bone destruction. Early treatment and longer sustained clinical remission prior to bone destruction are critical for full remission.

To determine whether weighting improves the correlation of ultrasound (US) score with serum matrix metalloproteinase-3 (MMP-3) level in rheumatoid arthritis (RA).As ultrasound examination was performed on 100 RA patients, and the severity of synovial effusion and synovial hypertrophy and the blood flow were semi-quantitatively graded from 0 to 3 by using the gray-scale (GS) and power Doppler (PD) modes. We then calculated the sums of the scores of the 28 joints of each patient in the 2 modes, that is, the GS28 and PD28 scores, as well as the respective scores weighted using the Lansbury articular index (LAI, shoulder and elbow, × 12; wrist, × 8; and knee, × 24)-Lans GS28 and Lans PD28 scores.The Lans PD28 score showed a higher correlation with MMP-3 (r = 0.591; 95% confidence interval, 0.446-0.705, p0.0001) than the existing measures. The scores of the large joints-the knee, shoulder, and elbow-correlated well with the serum MMP-3 level.Weighting with the LAI can improve the correlation of US findings with serum MMP-3 level. Bidirectional approach based on both serum MMP-3 level and US scores can further improve the assessment of disease activity in RA patients.

Objective The aim of this pilot study was to provide groundwork that could be utilized to optimize the global ultrasound (US) assessment of the whole joint for synovial pathologic features in patients with rheumatoid arthritis (RA). Methods US images of the second metacarpophalangeal joint in 8 predefined imaging planes, comprising regions that comprehensively capture the synovial pathologic features of the whole joint, were obtained from 30 patients with RA. Twelve experienced sonographers evaluated these images at the level of both the individual image and the whole joint, using a visual analog scale (VAS) to assess pathologic severity. Interrater reproducibility of the VAS scores was evaluated with intraclass correlation coefficients (ICCs), and factors that independently influenced the global assessment of the whole joint were identified using multiple linear regression analysis. Results A total of 14,276 VAS scores were analyzed. Interrater reproducibility of any eligible VAS assessment of synovial pathologic features was good (ICC 0.65). US assessment of synovial pathologic features in joints with mild inflammation was less reproducible than that in joints with severe inflammation. Although the most severely affected region in a joint did not always represent the average pathologic severity among the 8 regions, global assessment of the whole joint strongly correlated with assessment of the most severely affected region (P < 0.001). Importantly, the standard, midline imaging plane was not the most influential plane on the global assessment of the whole joint. Assessment of synovial fluid accumulation was not reproducible (ICCs 0.20–0.42) and did not substantially influence the global assessment of synovial inflammation (β = 0.06). Conclusion The results of this study provide a unique data set that could be utilized to optimize the global US assessment of synovial pathologic features of the whole joint in patients with RA.

Objective.Joint swelling, an important factor in the classification criteria and disease activity assessment in rheumatoid arthritis (RA), renders joint palpation a necessary skill for physicians. Ultrasound (US) examination that visualizes soft tissue abnormalities is now used to assess musculoskeletal disease. We assessed the usefulness of US assessments in enhancing physical joint examination skills.Methods.We examined 1944 joints (bilateral shoulder, elbow, wrist, metacarpophalangeal joints 1–5, and knee joints) in 108 patients with RA during April–July 2011. We first physically examined and confirmed joint swelling; subsequently, the same rheumatologist conducted US examinations and multiple assessors graded the joint swelling. When the 2 results differed, we received autofeedback from the US results to improve the physical examination skills.Results.The sensitivities and specificities of physical examination for US-detected swollen joint, the correlation coefficient (CC) of the swollen joint counts, and the concordance rate in each patient for joint swelling sites and power Doppler (PD)-positive sites with the κ coefficients between the physical and US examinations were compared over time. We found that the sensitivity of physical examination increased by 42 percentage points (pp), while the specificity decreased by 18 pp. The average CC in June–July was greater than that in April–May. The percentage of κ coefficients > 0.8 increased from 8.8% to 17% for joint swelling and from 8.3% to 14% for PD-positive sites.Conclusion.Our results suggest that autofeedback from US assessment provides quick improvement in palpation skills for identifying joint swelling in patients with RA.

Objective.To study the significance of anti-Ro/SSA antibodies (anti-Ro) in the clinical response to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA).Methods.The clinical responses of a cohort of 190 patients with RA who were treated with infliximab, etanercept, or adalimumab (n = 112, 64, and 14, respectively) as the first biologics were examined using the Disease Activity Score in 28 joints (DAS28) at 24 weeks and the discontinuation rate at 56 weeks. The baseline characteristics of responders and the nonresponders were compared. The clinical response was compared between anti-Ro-negative and -positive patients. The factors associated with the inefficiency of TNF inhibitors were estimated with a multivariable logistic regression analysis.Results.The positive rate of anti-Ro was significantly higher in patients with no European League Against Rheumatism (EULAR) response at 24 weeks (OR 3.64, 95% CI 1.45–9.01, p = 0.003). In anti-Ro-positive patients, a moderate or good EULAR response rate was significantly lower with a sustaining higher median DAS28 (p = 0.006), and this difference was greater among infliximab-treated patients. The discontinuation rate for TNF inhibitors due to inefficacy at 56 weeks was also higher in anti-Ro-positive patients (OR 4.68, 95% CI 1.82–11.99, p = 0.0005), and 75% of these patients received infliximab. The presence of anti-Ro was strongly associated with no EULAR response at 24 weeks and a higher discontinuation rate of TNF inhibitors by 56 weeks (OR 5.22, 95% CI 1.75–15.57, p = 0.003 and OR 10.18, 95% CI 2.18–49.56, p = 0.003).Conclusion.The presence of anti-Ro might be related to the lesser clinical response to infliximab compared to other TNF inhibitors, suggesting that the presence of anti-Ro should be considered when choosing the appropriate biologics for patients with RA.

We aim to examine changes in usage of nonbiologic, disease-modifying antirheumatic drugs (DMARDs) and evaluate their continuation rates in Japan. We analyzed DMARD treatment data for 3,734 patients with rheumatoid arthritis (RA) from 1998 to 2009 at Juntendo Hospital in Tokyo, Japan. The DMARD usage rate per month was determined to evaluate RA treatment history in the last decade. We also evaluated continuation rates of nonbiologic DMARDs in single and combination therapies and number of nonbiologic DMARD combination therapies used in each patient. We found that nonbiologic DMARD usage has dramatically changed in the last decade, with the most commonly used DMARD shifting from bucillamine to methotrexate (MTX). MTX showed the highest continuation rate; however, much lower continuation rate was observed when used alone rather than in combination treatments. Further, MTX was also used in the highest number of different combination therapies for a particular patient. These findings indicate that single MTX treatment may be unable to keep patients in clinical remission or lower disease activity compared with several combination therapies. Recent change in permitted maximum dosage of MTX from 8 to 16 mg/week may improve its efficacy and continuation rate in treating Japanese RA patients.

Background: Elderly patients with rheumatoid arthritis (RA) have more aging-related complications than nonelderly patients with RA. Objectives: The objective of the study was to investigate the treatment status of elderly patients with RA. Methods: Between January and March 2008, 969 patients with RA were enrolled in this observational cross-sectional study. Prescription of disease-modifying antirheumatic drugs (DMARDs) and corticosteroids and laboratory data related to RA, including matrix metalloproteinase 3, rheumatoid factor, and anti-cyclic citrullinated peptide antibody levels, were compared between the elderly and the nonelderly patients. Results: Fewer DMARDs were prescribed to the elderly patients (1.40 [SD, 0.57] vs. 1.51 [SD, 0.61]; P = 0.029). Furthermore, a lower percentage of patients received methotrexate (MTX) (47.2% vs. 56.9%; P = 0.0001), a lower average dosage of MTX was administered (5.46 [SD, 1.66] mg/wk vs. 5.96 [SD, 1.77] mg/wk; P = 0.0001), and fewer biologic DMARDs were used (1.46% vs. 5.59% for infliximab, P = 0.0008; 0.58% vs. 3.19% for etanercept, P = 0.0038) in the elderly group. The laboratory data suggested that the disease status was uncontrolled to a greater extent, and complications were more common in the elderly group. Conclusion: Elderly patients with RA receive less aggressive treatment than nonelderly patients with RA, despite laboratory evidence for poorly controlled disease status among the elderly. The use of a less aggressive regimen could be attributed to the higher prevalence of complications and problems. Therefore, the elderly with RA should be considered a different patient population from the viewpoint of treatment and be administered specialized medical care.

Leukocytapheresis (LCAP) is already being used in a clinical setting for the treatment of autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis, and it has been reported to be effective. However, it is totally or partially ineffective in some patients, which has forced clinicians to rethink therapeutic strategies and concurrent treatment. With the aim of enhancing the therapeutic effect, we carried out large volume leukocytapheresis, with a throughput of 5000 mL instead of the 3000-mL throughput of conventional leukocytapheresis in nine patients with rheumatoid arthritis resistant to methotrexate treatment. Using Cellsorba, the column filled with the unwoven fabric made of the polyethylene phthalate, a leukocyte removal filter, large volume leukocytapheresis was carried out once a week for a total of five sessions. The observation period was the 12-week period following completion of treatment. The American College of Rheumatology (ACR) core set was used for assessment of efficacy. Eight weeks after completion of treatment, a 20% improvement in ACR was observed in 77.8% (7/9) of subjects, a 50% improvement in ACR was seen in 55.6% (5/9) of subjects, and a 70% improvement in ACR was observed in 22.2% (2/9) of subjects. C-reactive protein decreased gradually as treatment progressed, and a significant decrease was observed 4 weeks after completion of treatment. The fact that some subjects had an ACR70 response, few reports of which are observed in the case of conventional leukocytapheresis, and the fact that the effect continued up to 12 weeks after completion of treatment suggests that the degree and duration of the effect of large volume leukocytapheresis might be longer than those of conventional leukocytapheresis.

A 60-year-old woman with rheumatoid arthritis had been treated with low-dose oral methotrexate (LD-oral-MTX), 6 mg weekly, for the past 2 years. She developed a 2-week history of progressive cognitive decline and blurred vision. On admission, she exhibited a confused state. Her visual acuity was light perception in the left-side and counting fingers in the right-side with no funduscopic abnormalities. Blood pressure, and serological and cerebrospinal fluid analyses, including renal function, vitamins and infectious diseases were normal. Cranial magnetic resonance imaging (MRI) and MR spectroscopy (MRS) showed abnormal findings that resolved spontaneously after the cessation of MTX and clinical improvements over several months (Fig. 1).

Background We reported that the presence of anti-Ro/SS-A antibody (anti-Ro) in rheumatoid arthritis (RA) patients might be related to the inefficacy and the discontinuation of infliximab (IFX) compared to the other TNF inhibitors (etanercept and adalimumab). In addition, anti-Ro-positive patients who did not respond to IFX or adalimumab improved clinically when they switched to etanercept or tocilizmab (TCZ) as the second biologics. Objectives To study the difference in clinical response between anti-Ro-positive and -negative RA patients treated with golimumab (GLM) that is one of the TNF inhibitors and TCZ that is IL-6 inhibitor. Methods Thirty-six patients with GLM treatment (naive: 15, switch: 21) and 38 patients with TCZ treatment (naive: 7, switch: 31) were studied the efficacy and the continuation rate. The baseline characteristics were compared between responders and non-responders. Clinical response according to the disease activity score in 28 joints (DAS28) EULAR response criteria at 24 and 48 weeks was compared between anti-Ro-positive and -negative patients with RA. Results The EULAR response of a moderate or good response at 24 weeks based on DAS28 score in GLM and TCZ treatment was 29/36 (80.6%) and 35/38 (85.7%), respectively. There was revealed similar pattern at 48 weeks both GLM and TCZ treatment (82.1% and 94.7%, respectively). The following variables at baseline that were sex, age, disease duration, methotrexate dose, steroid dose, CRP levels, ESR levels, and DAS28 were not different between responders and non-responders in both GLM and TCZ treatment. When the clinical efficacy was compared between naive and switch patients, the number of responders to TCZ treatment was not different between naive and switch (85.7% to 93.5%, respectively), while the response to GLM in naive was significantly higher than that in switch (100% to 65%; respectively, p=0.013). Anti-Ro was detected in 7 of 36 (19.4%) patients with GLM treatment, and detected in 10 of 38 (26.3%) patients with TCZ treatment. When we focused on the presence of anti-Ro, the EULAR response of a moderate or good response was not different between anti-Ro-positive and -negative patients treated with both GLM and TCZ at 24 and 48 weeks (24 weeks: GLM; 85. 7% vs. 70.4%; respectively, p=1.000, TCZ; 100% vs. 89.3%, respectively, p=0.552, 48 weeks: GLM; 71.4% vs. 70.4%; respectively, p=1.000, TCZ; 100% vs. 92.9%; respectively, p=1.000). The continuation rate to GLM and TCZ in anti-Ro-positive patients were 74.4% and 90.0%, respectively. Conclusions There was no difference efficacy between anti-Ro-positive and -negative RA patients with both treatments. The efficacy and the continuation rate of TCZ were better than that of GLM, in RA patients with both switched bio and anti-Ro. On the other hand, GLM was effective in RA patients with anti-Ro and it was suggested that the results might be related to the different immunogenicity between GLM and IFX. References Matsudaira R,et al. Anti-Ro/SS-A antibodies are an independent factor associated with an insufficient response to tumor necrosis factor inhibitors in patients with rheumatoid arthritis. J Rheumatol 2011; 38: 2346-54 Van Schouwenburg PA, et al. Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis. Nat Rev Rheumatol 2013; 9: 164-72 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3587

Background ARG098, a chimeric anti-Fas IgM monoclonal antibody, possesses a novel mode of action totally different from those of currently available RA therapeutics including cytokine targeting biologics. The Fas molecule (also known as APO-1 or CD95) mediates apoptosis in response to Fas ligand (Fas-L). Preclinical studies demonstrated that ARG098 specifically targets the Fas molecule leads to apoptosis in synoviocytes. Objectives An open-label sequential dose-escalation study of ARG098 was conducted to assess the safety and efficacy. Methods 43 patients diagnosed by the ACR criteria with knee joint synovitis were enrolled. The study had 7 dose groups from 0.01, 0.03, 0.1, 0.3, 1, 3 and 10 μg/knee, 6 patients in each group (7 patients in 10 μg) and single dose of ARG098 was intra-articularly administered to the target knee. Patients were required to be hospitalized at least 4 days after administration for close safety monitoring, and the assessment continued for 8 weeks with visit bases. Results The results showed that ARG098 was well-tolerated and no serious adverse events were observed. Total 33 adverse events (AEs) in 19 patients, and drug-related AEs in 9 patients which included non-clinical hepatological and cardiological findings were confirmed, however those were occurred in low frequency and the severity was all mild. ARG098 serum concentration was below the limit of qualification level ( Conclusions The safety of single intra-articular administration of ARG098 was well-confirmed up to 10 μg/knee and the pain VAS assessment and MRI showed improvements. However the dose dependency was not clearly observed. Repeat administration of ARG098 Phase IIa placebo-controlled trial is ongoing to determine the appropriate dosage and assessment methods. Disclosure of Interest None Declared

Background We previously reported that the presence of anti-Ro/SS-A antibody (anti-Ro) was an independent factor for poor clinical response to TNF-alpha inhibitors in patients with rheumatoid arthritis (RA). Objectives To investigate factors associated with normalized physical function, and clinical remission determined by simplified disease activity index (SDAI) at 54 weeks of infliximab (IFX) treatment in patients with RA. Methods We studied 114 patients with RA treated with IFX, and prospectively examined SDAI, Disease Activity Score in 28 joints (DAS28)/CRP, and modified Health Assessment Questionnaire Disability Index (mHAQ-DI). The clinical remission was defined with simplified disease activity index (SDAI) ≤3.3, and normal physical function was defined by mHAQ-DI Results Among 114 patients, 20 patients were withdrawn from this study because they had discontinued by 54 weeks (one was infection, one was reaction of allergy, and others were stopped IFX because of no efficacy). Age, gender, duration, SDAI and DAS28 at baseline were 50.14±13.15, 79 female/15male, 9.40±7.98, 4.19±1.14, and 25.43±12.78, respectively. In 94 patients, 17 (18.1%) and 33 (35.1%) were achieved remission defined with SDAI and DAS28/CRP, respectively. Normalized physical function, mHAQ Conclusions The prevalence of secondary SS and the presence of anti-Ro/SS-A antibodies before IFX treatment might associate with the outcome of poor physical function. To attain SDAI remission and normal physical function, tight control is necessary to prevent irreversible physical dysfunction. Disclosure of Interest None Declared