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Postoperative protocols after surgical treatment of calcaneal fracture have not been standardized to date. There are only a few reports on the efficacy of heel-unloading orthoses (HUOs; Mars shoe, Graffin orthosis), and thier efficacy is uncertain.The purpose of this study was to compare postoperative radiologic and clinical outcomes in patients with calcaneal fractures who used Graffin orthosis.Multicenter retrospective study.We finally extracted 182 patients from a database of the Trauma Research Group of Nagoya and divided them into two groups: group C (underwent casting or splinting only) and group O (Graffin orthosis was used). A propensity score algorithm was used to match group C to group O in a 1:1 ratio. We evaluated American Orthopaedic Foot and Ankle Society (AOFAS) score at three and six months after surgery and at final follow-up. Differences in reduction of the Böhler angle between the two groups were evaluated radiographically. All data were analyzed with a t-test or Fisher's exact test. P.05 was considered statistically significant.The AOFAS score 3 months after surgery in group O was significantly higher than that in group C (69.57 vs. 77.22; P = .004). However, there were no statistically significant differences between group C vs. group O in AOFAS scores at 6 months after surgery and at final follow-up (81.92 vs. 85.67 and 89.18 vs. 88.13; P = .087 and 0.597, respectively). There was no significant statistical difference in the reduction of the Böhler angle (5.07 vs. 5.89; P = .529).At 3 months postoperatively, the orthosis group showed predominantly better functional results. We believe that heel-unloading orthoses are useful for patients who require an early return to work and to daily life.

This study aimed to assess differences in implant failure and bone union rates, amount of change in alignment of lower extremities, and walking ability between early weight-bearing (EWB) and late weight-bearing (LWB) groups following retrograde intramedullary nailing (RIMN) for distal femoral fracture (AO/OTA 33) (DFF) at multiple centers using propensity score matching.The data of 213 patients who underwent RIMN from 2012 to 2019 in multiple tertiary hospitals were extracted from our database. Cases with the following factors were excluded: age60, open fracture, AO/OTA-type 33-C3 fracture, preoperative New Mobility Score (NMS) 3, postoperative follow-up3 months, and unknown weight-bearing start time. Eighty-four patients were divided into the EWB and LWB groups. EWB group patients were encouraged to perform partial weight-bearing walking at ≤4 weeks after surgery. LWB group patients were not allowed weight bearing for4 weeks after surgery. After propensity score matching was applied, 26 cases remained in each group.There were no cases of nail failure in either the EWB group or LWB group (P = 1). Screw failure occurred in 0 cases in the EWB group and in 1 case (4.5%) in the LWB group (P = 1.0). Non-union occurred in 5 patients (19.2%) in the EWB group and 4 patients (15.3%) in the LWB group (P = 1). The mean amount of change in lower extremities alignment did not differ between the two groups. The median Knee Society Score was 95.5 (59-100) vs. 93 (72-100) points (P = 0.39). The median NMS was 7 (0-9) vs. 7 (4-9) points (P = 0.82).There were no significant intergroup differences in the rates of implant failure, bone union at one year after surgery, amount of change in lower extremities alignment, or walking ability. We suggest that early weight bearing after RIMN for DFF may not be harmful in elderly people.

Resume Objectif Etudier les facteurs predictifs de poussee de polyarthrite rhumatoide (PR) apres arret du methotrexate chez des patients japonais presentant une faible activite stable de la maladie sous traitement combine de tocilizumab (TCZ) et methotrexate (MTX). Methodes Cette etude prospective multicentrique en ouvert non controlee porte sur des patients japonais atteints de PR presentant une faible activite de la maladie (indice CDAI [Clinical Disease Activity Index] ≤ 10) depuis ≥ 12 semaines sous traitement combine de TCZ et MTX. Le MTX a ete arrete apres 12 semaines d’administration toutes les deux semaines tandis que le TCZ etait maintenu. Une poussee de la maladie a ete definie comme soit un score CDAI > 10, soit l’administration d’un traitement de secours pour quelque cause que ce soit, meme avec un CDAI ≤ 10. L’influence des caracteristiques a l’inclusion sur les poussees de la maladie a la semaine 64 (52 semaines apres l’arret du MTX) a ete evaluee par des modeles de regression logistique. Resultats Des analyses d’efficacite ont ete effectuees chez 49 patients, dont 15 avaient presente une poussee de la maladie a la semaine 64. La proportion (intervalle de confiance [IC] a 95 %) de patients ayant une faible activite de la maladie sans poussee a la semaine 64 etait de 69,4 % (54,6–81,8 %). L’intervalle d’administration du TCZ etait plus long que celui indique sur l’etiquette au Japon (c.-a-d. administration par intraveineuse toutes les quatre semaines ou sous-cutanee toutes les deux semaines) chez 27 % des patients presentant une poussee et 6 % des patients sans poussee. Selon l’analyse multivariee, le sexe masculin (odds ratio [OR] 18,00, IC 95 % 2,80–115,56) et l’intervalle d’administration etendu du TCZ (OR 12,00, IC 95 % 1,72–83,80) etaient des facteurs predictifs independants de poussee de la maladie. Conclusion Les patients de sexe masculin et ceux recevant du TCZ selon un intervalle etendu presentent un risque eleve de poussee de la maladie apres l’arret du MTX concomitant. Numero d’enregistrement de l’essai jRCTs041180071, UMIN000021247.

Objectives Patients with rheumatoid arthritis (RA) usually switch to a second biological disease-modifying antirheumatic drugs (bDMARDs) when the first has proven to be ineffective, although some may discontinue bDMARDs treatment altogether. We investigated the total rate of bDMARDs retention and the risk of bDMARDs discontinuation in patients with RA. Methods The study included 564 patients with RA who started bDMARDs treatment before 2008 ( Results Among 564 patients, 74 had discontinued bDMARDs treatment due to AEs. Male sex and Steinbrocker class 3–4 were more frequent, while rheumatoid factor and concomitant methotrexate treatment were less frequent, in those aged ≥65 years than in those aged Conclusions Older patients are at higher risk of discontinuing bDMARDs treatment due to AEs than younger patients.

Glucocorticoids are important drugs used to treat rheumatoid arthritis. We recommend glucocorticoid discontinuation as soon as possible given the associated side-effects, but many patients continue to take oral glucocorticoids long-term. The present study aimed to explore factors associated with glucocorticoid discontinuation at 52 weeks after initiating biological disease-modifying antirheumatic drugs (bDMARDs). Subjects were 564 patients from a Japanese multicenter registry who were administered glucocorticoids and methotrexate (MTX) followed by initiation of the first bDMARD. We examined the status of oral glucocorticoid use at 52 weeks after initiating the first bDMARD. By 52 weeks after bDMARD initiation, 164 patients (29.1%) discontinued glucocorticoids. Multivariable analysis identified age, MTX dose, and glucocorticoid dose as factors independently associated with glucocorticoid discontinuation. After adjusting for baseline characteristics using propensity score matching, among patient groups administered MTX ≤ 8 mg/week and MTX > 8 mg/week, 105 pairs remained. A significantly higher rate of glucocorticoid discontinuation (41.0%) was noted for patients administered MTX > 8 mg/week. Our findings suggest that glucocorticoids may be discontinued after initiating bDMARDs. Moreover, higher MTX doses (>8 mg/week) at the time of bDMARD initiation were associated with glucocorticoid discontinuation among patients treated with bDMARDs.

This study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan–Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.

Objectives The study aimed to investigate the effectiveness and tolerance of biological disease-modifying antirheumatic drugs (bDMARDs) therapy administered concomitantly with tacrolimus (TAC) treatment in patients with rheumatoid arthritis. Methods 2792 patients who underwent therapy with five bDMARDs (etanercept: ETN, adalimumab, golimumab, tocilizumab, and abatacept: ABT) were enrolled. Among the study subjects, 1582 were concomitant methotrexate (MTX group), 147 were concomitant TAC (TAC group), and 1063 were non-concomitant MTX and TAC (non-MTX/TAC group). The primary outcome was the incident rate of discontinuation of bDMARDs by adverse events (AEs) or loss of efficacy. Results Concerning the analysis for each reasons of discontinuation, including AEs and loss of efficacy, the hazards ratio (HR) was significantly lower in the TAC group than in non-MTX/TAC groups (AEs: HR = 0.39, 95% confidence interval, 0.23–0.68, loss of efficacy: HR = 0.49, 95% confidence interval, 0.30–0.78). The loss of efficacy with the use of ETN and ABT was lower in the TAC group than in non-MTX/TAC groups. Concomitant TAC did not induce elevated risk for discontinuation of AEs in all bDMARD analyses. Conclusions Concomitant TAC with ABT or ETN showed higher retention rates than bDMARDs therapy without TAC or MTX. AEs did not increase over long-term observation.

Discontinuation of biologic therapy in rheumatoid arthritis is attributable to various reasons, with the most important cause being insufficient response. In this study, we investigated the association between rheumatoid factor (RF) and anti-citrullinated protein autoantibody (ACPA) status and the discontinuation of tumor necrosis factor inhibitors (TNFi) therapy due to insufficient response in bio-naïve rheumatoid arthritis (RA) patients.This study included patients enrolled in the Tsurumai Biologic Communication Registry in Japan. The crude comparison of TNFi discontinuation due to ineffectiveness between seropositive and seronegative patients was analyzed using the cumulative incidence function of competing events and Gray test. We assessed the associations between baseline patient characteristics and discontinuation of TNFi therapy due to insufficient response using Fine-Gray proportional hazard regression. Fine-Gray proportional hazard analysis considered competing events of interest, including insufficient response, adverse event, palliation, and personal reasons.Of 1237 patients evaluated, 79.3% were positive for RF and 85.4% for ACPA; 72.6% were double positive and 11.1% were double negative. TNFi therapy had been discontinued because of insufficient response at 200 weeks in 19.8% RF-positive, 16.7% RF-negative, 23.0% ACPA-positive, and 13.8% ACPA-negative patients. There was a significantly higher discontinuation rate due to insufficient response in ACPA-positive patients than in ACPA-negative patients using Gray test, with a similar trend as that for RF status. RF positivity was significantly predictive of the discontinuation of TNFi therapy due to ineffectiveness using Fine-Gray proportional hazard regression analysis after adjusting for baseline characteristics, including age, sex, stage, class, disease activity at baseline, methotrexate use, and prednisolone use [hazard ratio 1.73 (95% confidence interval 1.07-2.80)].Using Fine-Gray proportional hazard regression, we demonstrated that RF positivity was related to a higher discontinuation rate of TNFi therapy due to ineffectiveness in bio-naïve RA patients. Key Points • RF positivity is related to a higher discontinuation rate of TNFi therapy due to ineffectiveness. • ACPA is not predictive of a discontinuation of TNFi therapy due to ineffectiveness.

To compare the clinical outcomes of abatacept between rheumatoid arthritis patients with and without concomitant methotrexate (MTX) treatment in daily clinical practice. A retrospective cohort study was performed using data from a multicentre registry. A total of 176 consecutive rheumatoid arthritis patients treated with abatacept were included. The propensity score based on multiple baseline characteristic variables was calculated, and 41 of 86 patients treated without MTX (MTX(−)) and 41 of 90 patients treated with concomitant MTX (MTX(+)) were statistically extracted and analysed. Clinical outcomes were evaluated and compared between the two groups over a 52-week period. Baseline characteristics were statistically comparable. No significant differences were observed in the following clinical outcomes from baseline throughout the 52-week period: drug retention rate (MTX(−)/MTX(+) 79.1%/80.5%), mean change in disease activity score based on 28 joints (DAS28-CRP) from baseline (− 1.35/− 1.54), low disease activity rate (48.8%/43.9%), clinical remission rate (31.7%/36.6%), moderate European League Against Rheumatism (EULAR) response rate (68.3%/68.3%), and good EULAR response rate (36.6%/41.1%) at 52 weeks. In rheumatoid arthritis patients with similar background characteristics undergoing abatacept treatment, concomitant MTX does not seem to affect clinical outcomes. Abatacept would be a suitable treatment option in daily clinical practice in patients with contraindications to MTX. • This is the first study to directly compare the clinical efficacy and safety of abatacept between patients with and without concomitant methotrexate (MTX) treatment in ‘real-world’ settings using the propensity score matching method. • There were no significant differences in clinical outcomes of abatacept between patients with and without concomitant MTX treatment. • We used data from a large Japanese multicentre registry for biologics in rheumatoid arthritis, thereby decreasing selection bias based on the personal preferences of physicians.

This study aimed to evaluate the effectiveness of abatacept (ABA) by anti-cyclic citrullinated peptide (ACPA) status on disease activity as well as radiographic progression in patients with rheumatoid arthritis (RA) in clinical settings. A retrospective cohort study was conducted using data from a multicenter registry. Data from a total of 553 consecutive RA patients treated with intravenous ABA were included. We primarily compared the status of disease activity (SDAI) and radiographic progression (van der Heijde modified total Sharp score: mTSS) between the ACPA-negative (N = 107) and ACPA-positive (N = 446) groups. ‘ACPA positive’ was defined as ≥ 13.5 U/mL of anti-CCP antibody. Baseline characteristics between groups were similar. The proportion of patients who achieved low disease activity (LDA; SDAI ≤ 11) at 52 weeks was significantly higher in the ACPA-positive group. Multivariate logistic regression analysis identified ACPA positivity as an independent predictor for achievement of LDA at 52 weeks. Drug retention rate at 52 weeks estimated by the Kaplan–Meier curve was significantly higher in the ACPA-positive group. Achievement rate of structural remission (ΔmTSS ≤ 0.5) at 52 weeks was similar between groups. ABA treatment demonstrated a significantly higher clinical response and higher drug retention rate in ACPA-positive patients. Progression of joint destruction was similar between the ACPA-negative and ACPA-positive groups. Close attention should be paid to joint destruction even in patients showing a favorable response to ABA, especially when the ACPA status is positive.

Objective To investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy. Methods Participants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index [CDAI] ≤ 10) for ≥ 12 weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12 weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score > 10 or intervention with rescue treatments for any reason even if the CDAI score was ≤ 10. The impact of baseline characteristics on disease flare at week 64 (52 weeks after methotrexate discontinuation) was assessed with logistic regression models. Results Efficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval [CI]) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6–81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4 weeks, or subcutaneously every 2 weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio [OR]: 18.00, 95% CI: 2.80–115.56) and extended dosing interval of tocilizumab (OR: 12.00, 95% CI: 1.72–83.80) were independent predictors of disease flare. Conclusion Male patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate. Trial registration number jRCTs041180071, UMIN000021247.

Objectives: To evaluate the efficacy and safety of methotrexate (MTX) discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing combinati...

To explore predictive factors including MMP-3 for achievement of low disease activity (LDA) at 52 weeks in bio-switch rheumatoid arthritis (RA) patients treated with abatacept, for whom obtaining a good clinical response can be difficult.Participants were 423 consecutive patients with RA treated with abatacept who were observed for longer than 52 weeks and registered in the TBCR, a Japanese multicentre registry system. Multivariate logistic regression analysis was used to study factors that predict the achievement of LDA at 52 weeks in bio-naïve (n=234) and bio-switch (n=189) groups.ROC analysis revealed that MMP-3 improvement rates at 12 weeks in bio-switch patients had the highest AUC with a cut-off value of 20.0% for predicting LDA achievement at 52 weeks. Multivariate logistic regression analysis revealed that, in addition to DAS28-CRP at baseline, achieving 20% improvement in MMP-3 levels at 12 weeks was an independent predictive factor (adjusted OR: 4.277, p=0.003) in the bio-switch group, whereas DAS28 was the only predictor in the bio-naïve group. Patients who achieved 20% improvement in MMP-3 levels at 12 weeks had significantly higher achievement rates of LDA at 52 weeks compared to those who did not achieve 20% improvement in the bio-switch group (60.0 vs. 33.3%, p=0.001).Our findings suggest that improvement in MMP-3 levels is key to predicting the clinical efficacy of abatacept. Closer attention paid not only to major clinical indices, but also changes in MMP-3 levels, could improve our ability to optimise clinical results when treating bio-switch patients.

Objective: To study the clinical effectiveness and long-term retention rate of abatacept (ABA) in elderly rheumatoid arthritis (RA) patients in daily clinical practice.Methods: A retrospective cohort study was performed using data from a multicenter registry. Our study population comprised 500 consecutive RA patients treated with ABA. We compared clinical effectiveness and ABA retention rates between the Young (≤62 years), Middle (62 to 72 years), and Elderly (≥72 years) groups. We also performed separate examinations to identify predictive factors for ABA discontinuation in those with versus those without concomitant methotrexate (MTX) treatment.Results: Mean age was 52.7 years in the Young group, 67.7 years in the Middle group, and 78.1 years in the Elderly group. No significant group-dependent differences were found in mean DAS28 score, categorical distribution of DAS28, and EULAR response rate across the 52 weeks. The ABA retention rates at three years as determined by the Kaplan-Meier method were similar in all three groups. Patient age was not a significant predictor of ABA discontinuation due to adverse events in patients with concomitant MTX; however, it was found to be a significant predictor for those who did not use MTX (Cox hazard model).Conclusion: ABA would be a reasonable treatment option for elderly RA patients from the viewpoints of both clinical effectiveness and long-term retention. However, physicians should watch carefully for any serious adverse reactions in elderly RA patients with intolerance to MTX.

Objective To determine the effects of concomitant methotrexate (MTX) on the incidence of large joint replacement resulting from the progression of large joint destruction in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors. Methods A retrospective cohort study was performed using a multicenter registry. In total, 803 patients with RA who received etanercept or adalimumab were included. The first large joint replacement during treatment with etanercept or adalimumab was used as the outcome variable in predictive analyses. The cumulative incidence of large joint replacement was estimated using Kaplan-Meier curves, and the impact of concomitant MTX on the incidence of large joint replacement was assessed with Cox proportional hazards models. Propensity score matching was used to reduce selection bias. Results Of all patients, 601 (75%) received concomitant MTX at a median dosage of 8 mg/week (interquartile range 6–8). A total of 49 patients (62 joints) underwent large joint replacement during treatment with etanercept or adalimumab. The incidence of large joint replacement for patients with concomitant MTX was significantly lower than that for patients without MTX (P < 0.001). Multivariate analysis revealed that concomitant MTX independently predicted large joint replacement (hazard ratio 0.36, 95% confidence interval 0.20–0.65). Additionally, propensity score–matched analysis demonstrated that patients with concomitant MTX had a significantly lower incidence of large joint replacement than those without concomitant MTX (P = 0.032). Conclusion Concomitant MTX reduces the incidence of large joint replacement in patients with RA treated with TNF inhibitors.

This observational retrospective study examined whether abatacept efficacy could be augmented with concomitant methotrexate (MTX) or tacrolimus (TAC) in patients with rheumatoid arthritis (RA) who experienced failure with prior biological disease-modifying antirheumatic drugs (DMARDs) and in whom favorable therapeutic efficacy is difficult to achieve. All patients with a prior biological DMARD history who were treated with abatacept for 52 weeks and registered in a Japanese multicentre registry were included. Clinical efficacy and safety of abatacept according to the concomitant drug used, i.e., none (ABT-mono), MTX (ABT-MTX), and TAC (ABT-TAC), were compared. A greater mean percent change of DAS28-ESR was observed in the ABT-TAC group compared with the ABT-mono group at weeks 12 (-20.5 vs. -5.4 %, p = 0.035) and 24 (-25.0 vs. -11.0 %, p = 0.036). ABT-MTX and ABT-TAC groups had a significantly higher proportion of patients who achieved low disease activity (LDA) within 52 weeks compared with the respective baselines, while no significant change was observed in the ABT-mono group. A higher proportion of patients in the ABT-TAC group achieved EULAR moderate response compared with the ABT-mono group at week 52 (66.7 vs. 35.0 %, p = 0.025). Multivariate logistic regression analysis revealed that concomitant TAC use was independently associated with the achievement of LDA and EULAR response at 52 weeks, while concomitant MTX use was not. Concomitant TAC use may offer a suitable option for RA patients treated with abatacept after prior biological DMARD failure, likely because both abatacept and TAC affect T cell activation.

Objective: This study aimed to investigate predictors of biologic discontinuation due to insufficient response as a surrogate for relapse in patients with rheumatoid arthritis (RA) who achieved clinical remission with biologic treatment. Methods: This study was performed based on data from a multicenter registry, and included 404 patients who achieved clinical remission within the first year of treatment with their first biologic. Cumulative retention rate of the first biologic was estimated using Kaplan–Meier curves, and the impact of patient characteristics on biologic discontinuation was assessed with Cox proportional hazards models. Results: During follow-up, 50 patients discontinued their first biologic due to insufficient response. Overall discontinuation rates due to insufficient response after achieving remission were 6%, 11%, and 19% at 1, 2, and 5 years, respectively. Multivariate analysis revealed that concomitant glucocorticoids at achieving remission [hazard ratio (HR): 3.80, 95% confidence interval (CI): 1.89–7.64)] and a higher level of C-reactive protein (CRP) at achieving remission (HR: 1.47 per 1 mg/dL, 95% CI: 1.09–1.99) independently predict discontinuation due to insufficient response after achieving remission. Conclusion: Patients with RA who achieved remission with concomitant glucocorticoid treatment and a higher level of CRP are at high risk of subsequent biologic discontinuation due to insufficient response., Published online: 13 Jul 2017

OBJECTIVE Only a few studies have assessed predictive factors for the long-term efficacy of abatacept. This study aimed to provide clinical evidence of an adequate observational period for predicting low disease activity (LDA) achievement at 52 weeks in RA patients treated with abatacept. METHODS Participants were all patients registered in a Japanese multicentre registry who were treated with abatacept and had at least 52 weeks of follow-up (n = 254). RESULTS Areas under the receiver operating characteristic curves for the 28-joint count with CRP (DAS28-CRP) at each time point for LDA achievement at 52 weeks were: 0.686 (cut-off score: 4.6) at baseline, 0.780 (3.8) at 4 weeks, 0.875 (3.3) at 12 weeks, and 0.900 (3.0) at 24 weeks. Although patients with a DAS28-CRP score < 3.0 at 24 weeks had the highest proportion of LDA achievement at 52 weeks (79.3%), the proportion for those with a score < 3.3 at 12 weeks was comparable (77.2%, P = 0.697). Proportions were significantly lower in patients with a score < 3.8 at 4 weeks or < 4.6 at baseline. Multivariate logistic regression demonstrated that a DAS28 score of < 3.3 at 12 weeks was an independent strong predictor for LDA at 52 weeks (adjusted odds ratio: 15.2, P < 0.001). CONCLUSION Twelve weeks is an adequate observational period to judge the long-term clinical efficacy of abatacept, and is about as early as the period for assessing TNF blockade therapy.

The purpose of this study was to explore drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors (TNFi) in clinical practice in patients with rheumatoid arthritis (RA) on low-dose methotrexate (MTX) or without MTX.A total of 169 RA patients who had been withdrawn from first-course TNFi therapy and received a different TNFi or tocilizumab (TCZ) as a second biologic agent were selected from the Tsurumai Biologics Communication Registry, an observational cohort database. Retention rates of second biologic treatment were compared by the type of first TNFi and second biologic agents.Eighty-six patients received first-course infliximab (IFX) or adalimumab (ADA) therapy, and 83 patients received first-course etanercept (ETN) therapy. The former group had a significantly higher retention rate (IFX, 81.1%; ADA, 83.3%) of the second biologic therapy compared to the latter (56.6%, p0.001, log-rank test). Drug retention rates of the second biologic agent after switching from IFX/ADA were significantly higher with ETN (90.0%) and TCZ (94.7%) than with ADA/IFX (59.3%). Drug retention rates of the second biologic agent after switching from ETN were significantly higher with TCZ (75.9%) than with ADA/IFX (46.3%). The differences were significant even after adjusting for baseline clinical variables using the Cox proportional hazards model.Drug retention rates of IFX and ADA after switching from the first TNFi were significantly lower compared to those of ETN and TCZ in patients on low-dose MTX or without MTX.

The purpose of this study was to identify the effects of concomitant use of MTX and baseline characteristics for remission in the treatment of RA with tocilizumab (TCZ) in daily clinical practice.A total of 240 RA patients who received TCZ were selected from the multicentre Tsurumai Biologics Communication Registry. Predictive baseline factors for remission [28-item DAS (DAS28)2.6] at 52 weeks were determined by logistic regression analysis. To confirm whether the associations varied by the level of baseline disease activity, we also assessed the model including the interaction term (each baseline variable × DAS28).In total, 49.3% of the study participants used MTX with TCZ. Even after controlling for the baseline DAS28, shorter disease duration (≤3 year) [odds ratio (OR) 3.58 (95% CI 1.81, 7.07)], less structural damage [Steinbroker stage ≤II, OR 2.33 (95% CI 1.32, 4.12)] and concomitant prednisolone use [OR 0.38 (95% CI 0.21, 0.68)] showed significant predictive values for remission. Concomitant MTX use failed to show a significant association with remission, whereas a significant interaction was observed among concomitant MTX use × DAS28 (P = 0.006). In patients with high baseline disease activity (DAS285.1), concomitant MTX use was associated with increased odds for remission [adjusted OR for all baseline variables 2.54 (95% CI 1.11, 5.83)], while no association was indicated between them in patients with low to moderate baseline disease activity (DAS28 ≤ 5.1).Concomitant MTX use is an important component of TCZ treatment for RA patients with high disease activity.

The aim of this study was to compare the efficacy and retention rates of three biologics (abatacept, tocilizumab, and etanercept) after switching from first-course anti-TNF monoclonal antibody therapy. We performed a retrospective multicenter study of 89 patients who underwent second-course biologic therapy for 52 weeks after switching from first-course anti-TNF monoclonal antibody therapy. Patients at baseline had a mean age of 58.7 years, mean disease duration of 9.8 years, and mean clinical disease activity index (CDAI) of 22.4. There was no significant difference between the three drugs, except in rheumatoid factor positivity. Retention rates for abatacept, tocilizumab, and etanercept treatment at 52 weeks were 72.0, 89.5 and 84.6 %, respectively. The evaluation of CDAI indicated no significant difference at 52 weeks among the three drugs. Discontinuation due to all unfavorable causes did not significantly differ among the three drugs in hazard ratio-based evaluations. Our results show that patients treated with abatacept, tocilizumab, and etanercept achieved a high response rate with no significant differences in drug retention rates and clinical efficacy. These drugs represent good therapeutic options for patients with RA who are refractory to anti-TNF monoclonal antibody therapy.

Objective We previously reported that depression and inflammation have independent effects on pain severity in patients with rheumatoid arthritis (RA). Alexithymia is a personality trait characterized by deficits in cognitive processing and regulation of emotions. A broad association between alexithymia and various health problems has been suggested, including depression, inflammation, and pain. The objective of this study was to examine the independent influence of alexithymia on pain perception and its relationship to depression and inflammation. Methods We evaluated 213 RA outpatients who completed self-administered questionnaires, including the Beck Depression Inventory-II (BDI-II) to measure depression severity, the 20-item Toronto Alexithymia Scale (TAS-20) to measure degree of alexithymia, and a visual analog scale to quantify perceived pain. Serum C-reactive protein (CRP) levels were measured to quantify inflammation severity. Results An initial significant positive association between the TAS-20 score and pain severity (P = 0.01) lost significance after controlling for BDI-II score and CRP level using regression analysis. An interaction was observed among alexithymia, depression, and inflammation with regard to perceived pain. Among those without alexithymia, pain severity increased linearly with the CRP tertile levels regardless of the presence of depression (P < 0.001 for trend). No linear association between pain severity and CRP level was observed among those with alexithymia. Moreover, depressed patients with alexithymia (BDI-II score ≥14 and TAS-20 score ≥61) reported severe pain even at low CRP levels. Conclusion Alexithymia might have a substantial role in pain perception as well as depression in patients with RA. A biopsychosocial approach is essential to achieve better pain control.

Rheumatoid synovial fibroblasts (RSF) are activated by toll-like receptor (TLR) signaling pathways during the pathogenesis of rheumatoid arthritis (RA). Cathepsin K is highly expressed by RSF, and is known to play a key role in the degradation of type I and type II collagen. Cathepsin K is considered to be implicated in the degradation of bone and cartilage in RA. Recent observations have shown that hyaluronan (HA) is an important inhibitor of inflammation. In the present study, we show that lipopolysaccharide (LPS) stimulation significantly increases cathepsin K expression by real-time PCR and western blotting analysis via a TLR-4 signaling pathway. Furthermore, we demonstrate that HA suppresses LPS-induced cathepsin K expression, which is dependent on CD44 but not intercellular adhesion molecule-1 (ICAM-1) interaction. We also show that HA suppresses LPS-induced matrix metalloproteinase-1 (MMP-1) expression, which is dependent on both CD44 and ICAM-1 interaction. We conclude that the anti-inflammatory effect of HA occurs through crosstalk between more than one HA receptor. Our study provides evidence for HA mediated suppression of LPS-induced cathepsin K and MMP-1 expression, supporting a protective effect of HA in RA.

Objective To explore the effect of hyaluronan oligosaccharides (HAoligos) on interactions between HA and its principal receptor, CD44, in rheumatoid synovial fibroblasts (RSFs) and matrix metalloproteinase (MMP) production. Methods RSFs were isolated from rheumatoid synovial tissue. HA distribution was visualized by immunocytochemistry. MMP-1 and MMP-3 induction was analyzed by real-time RT-PCR and immunoblotting. The interaction between HAoligos and their MMP-producing receptors was tested by blocking with anti-CD44 and anti-Toll-like receptor 4 (TLR-4). Phosphorylation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) was analyzed by immunoblotting. Results Endogenous HA decreased after treatment with HAoligos, while MMP-1 and MMP-3 expression increased in a dose-dependent manner. Pretreatment with anti-CD44 or anti-TLR-4 antibody significantly reduced the effect of HAoligos on MMP-1 and MMP-3 mRNA expression. NF-κB and p38 MAPK phosphorylation was enhanced by HAoligos pretreated with anti-TLR-4, and HAoligo-induced MMP production was blocked with an inhibitor of NF-κB and p38 MAPK pathways. Conclusions Disruptive changes in CD44-HA interactions by HAoligos enhanced MMP-1 and MMP-3 production via activation of NF-κB and p38 MAPK signaling pathways in RSFs.

To determine the effects of concomitant methotrexate (MTX) on the incidence of large joint replacement resulting from the progression of large joint destruction in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors.A retrospective cohort study was performed using a multicenter registry. In total, 803 patients with RA who received etanercept or adalimumab were included. The first large joint replacement during treatment with etanercept or adalimumab was used as the outcome variable in predictive analyses. The cumulative incidence of large joint replacement was estimated using Kaplan-Meier curves, and the impact of concomitant MTX on the incidence of large joint replacement was assessed with Cox proportional hazards models. Propensity score matching was used to reduce selection bias.Of all patients, 601 (75%) received concomitant MTX at a median dosage of 8 mg/week (interquartile range 6-8). A total of 49 patients (62 joints) underwent large joint replacement during treatment with etanercept or adalimumab. The incidence of large joint replacement for patients with concomitant MTX was significantly lower than that for patients without MTX (P0.001). Multivariate analysis revealed that concomitant MTX independently predicted large joint replacement (hazard ratio 0.36, 95% confidence interval 0.20-0.65). Additionally, propensity score-matched analysis demonstrated that patients with concomitant MTX had a significantly lower incidence of large joint replacement than those without concomitant MTX (P = 0.032).Concomitant MTX reduces the incidence of large joint replacement in patients with RA treated with TNF inhibitors.

Objective.Assessing retention rate and risk factor for drug discontinuation is important for drug evaluation. We examined a 3-year retention rate and the risk factor for discontinuation due to insufficient efficacy (IE) and adverse events (AE) in Japanese patients with rheumatoid arthritis (RA) who are receiving etanercept (ETN).Methods.Data were collected from 588 patients treated with ETN as a first biologic from the Tsurumai Biologics Communication Registry. Baseline characteristics for the incidence of both IE and AE were analyzed using the Cox proportional-hazards regression model. Patients were divided into groups based on age and concomitant methotrexate (MTX). Drug retention rates were calculated using the Kaplan-Meier method and compared among groups using the log-rank test.Results.ETN monotherapy without concomitant MTX [MTX(–)] was significantly related to a higher incidence of discontinuation due to IE [hazard ratio (HR) = 2.226, 95% CI 1.363–3.634]. Older age and MTX(–) were significantly related to a higher incidence of discontinuation due to AE [HR = 1.040, 1.746, 95% CI 1.020–1.060, 1.103–2.763, respectively]. The MTX(–)/≥ 65 years group had the lowest retention rate (p < 0.001). The discontinuation rate due to IE was lower in the MTX(+)/< 65 years group compared to < 65 years/MTX(–), ≥ 65 years/MTX(–) group (p = 0.006, p < 0.001, respectively). The discontinuation rate due to AE was highest in the MTX(–)/≥ 65 years group (p < 0.001).Conclusion.Our findings suggest that the risk of discontinuation due to IE was high in the patients who did not use concomitant MTX and that the risk of discontinuation due to AE was high in elderly patients who did not use concomitant MTX.

We previously reported that depression and inflammation have independent effects on pain severity in patients with rheumatoid arthritis (RA). Alexithymia is a personality trait characterized by deficits in cognitive processing and regulation of emotions. A broad association between alexithymia and various health problems has been suggested, including depression, inflammation, and pain. The objective of this study was to examine the independent influence of alexithymia on pain perception and its relationship to depression and inflammation.We evaluated 213 RA outpatients who completed self-administered questionnaires, including the Beck Depression Inventory-II (BDI-II) to measure depression severity, the 20-item Toronto Alexithymia Scale (TAS-20) to measure degree of alexithymia, and a visual analog scale to quantify perceived pain. Serum C-reactive protein (CRP) levels were measured to quantify inflammation severity.An initial significant positive association between the TAS-20 score and pain severity (P = 0.01) lost significance after controlling for BDI-II score and CRP level using regression analysis. An interaction was observed among alexithymia, depression, and inflammation with regard to perceived pain. Among those without alexithymia, pain severity increased linearly with the CRP tertile levels regardless of the presence of depression (P0.001 for trend). No linear association between pain severity and CRP level was observed among those with alexithymia. Moreover, depressed patients with alexithymia (BDI-II score ≥14 and TAS-20 score ≥61) reported severe pain even at low CRP levels.Alexithymia might have a substantial role in pain perception as well as depression in patients with RA. A biopsychosocial approach is essential to achieve better pain control.

Background In recent years, it has been reported that baseline anti-cyclic citrullinated peptide (CCP) antibody positivity is associated with a better response and retention rate in patients with rheumatoid arthritis (RA) [1,2]. However, there have been few reports describing the association of prognostic factors with the long-term clinical results represented by drug retention rate. Objectives The aim of this study was to identify prognostic factors for abatacept (ABT) retention in clinical routine practice using data from a Japanese multicenter registry system for RA patients treated with biological DMARDs. Methods All eligible RA patients who underwent ABT therapy from October 2010 through to March 2015 (n=513) were prospectively registered in the Tsurumai Biologics Communication Registry (TBCR). Potential prognostic factors such as baseline demographics and disease characteristics were analyzed using Log-rank test. Variables with a p value of Results The overall retention rate was 58.2% (95% CI; 0.49 - 0.66) at 4 years. Based on Log-rank test, previous biologics treatment (naive vs. switch), Steinbrocker stage (1–2 vs. 3–4), RF status (negative vs. positive), anti CCP antibody status (negative vs positive) and concomitant MTX use (user vs. non-user) were eligible to enter the multivariate model (Table 1). Multivariable analysis revealed that patients had a significantly lower risk of ABT discontinuation if they were biologic-naive (HR; 0.57, 95%CI; 0.35 - 0.91) and anti-CCP antibody positive (HR; 0.57, 95%CI; 0.32 - 0.99) (Table2). Furthermore, we divided anti-CCP antibody status into three categories ( Conclusions This study demonstrated that baseline anti-CCP antibody positivity is associated with a better long-term retention of ABT therapy. But additional therapeutic intervention would be necessary for patients with high titer to improve the short- and long-term clinical results of ABT. References Sokolove J, et al. Ann Rheum Dis 2015; 0: 1–6 Nuesslein H, et al. BMC Musculoskeietal Disorders 2015; 16: 176–186 Disclosure of Interest M. Hanabayashi: None declared, N. Takahashi: None declared, Y. Yokota: None declared, H. Miyake: None declared, T. Kojima Speakers bureau: Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, abbvie, Bristol-Myers Squibb, Pfizer, Janssen Pharmaceutical K.K. and UCB Japan Co. Ltd., N. Ishiguro Speakers bureau: Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, abbvie, Bristol-Myers Squibb, Pfizer, Janssen Pharmaceutical K.K. and UCB Japan Co. Ltd.

Background After demonstration of clinical outcome of abatacept (ABT) therapy, the use of ABT has become common practice in treating patients with rheumatoid arthritis (RA). The clinical trials has been reported that the efficacy was superior in biologic naive patients than that in patients failed to prior biologics, but a few data exist regarding the differences between single biologic failure and multiple biologic failure. Objectives The aim of this study was to assess whether the number of previous biologic therapy had any impact on the efficacy and safety of ABT in clinical routine practice. Methods All eligible patients who underwent ABT therapy from October 2010 through to September 2014 (n=193) were registered in the Tsurumai Biologics Communication Registry (TBCR group), an RA research consortium that consists of Nagoya University Hospital and 18 affiliated institutes. We compared disease activities using DAS28 CRP between single biologic failure (single-BF group; n=118) and multiple biologic failure (multiple-BF group; n=75) at week 0, 12, 24, 52 104 and 156. Drug retention rates were calculated by Kaplan-Meier method. Furthermore, discontinuation due to inadequate responses (IRs) and adverse events (AEs) were evaluated. Results In the baseline characteristics data, there was no significant difference between single-BF group and multiple-BF group, except for body weight (51.6 vs. 59.2kg). At any observation point, mean DAS28 CRP values were quite similar between two groups (data not shown). Drug retention rate at week 156 was 58.5% in single-BF group and 60.0% in multiple-BF group (Figure 1). The discontinuation rate due to IRs in single-BF group was slight higher than that in multiple-BF group (26.3 vs. 17.3%, Log-rank test p=0.127; Figure 2). Conversely, the discontinuation rate due to AEs was lower in single-BF group (4.20 vs. 12.0%, Log-rank test p=0.063; Figure 3). Conclusions This study demonstrated that the number of previous biologic therapy had less affected on retention rate of ABT. Interestingly, disease activities were quite similar between single biologic failure and multiple biologic failure. Our results suggest that ABT would be beneficial for patients with multi biologic failure. Disclosure of Interest M. Hanabayashi: None declared, N. Takahashi: None declared, H. Miyake: None declared, Y. Yokota: None declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, abbvie, Bristol-Myers Squibb, Pfizer, Janssen Pharmaceutical K.K. and UCB Japan Co. Ltd., N. Ishiguro Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, abbvie, Bristol-Myers Squibb, Pfizer, Janssen Pharmaceutical K.K. and UCB Japan Co. Ltd.

Background In recent years, abatacept (ABT) has become used as the first biologic agent for patients with RA. The long term efficacy and safety of ABT in patients without previous biologic therapy has been reported in clinical trials, but still uncertain in clinical routine practice. Objectives In this paper, we studied the 3-year outcomes of ABT therapy in biologic naive patients (Naive group) and patients failed to prior biologics (Switch group) to demonstrate the “real-world” data using our registry system. Methods All RA patients who were initiated ABT therapy from October 2010 through to October 2011 (n=134) at Nagoya University Hospital and 18 other institutes (Tsurumai Biologics Communications Registry: TBCR group) were enrolled in this study. We compared disease activities using DAS28 CRP between Naive group (n=57) and Switch group (n=77). Furthermore, discontinuation due to inadequate responses (IRs) and adverse events (AEs) were evaluated. Results In the baseline characteristics data, there were several differences between Naive and Switch group, such as age (66.5 vs. 61.2 years old), disease duration (8.5 vs. 13.3 years), distribution of Steinbrocker classification stage, tacrolims user (3.6 vs. 15.8%) and prednisolone user (44.6 vs. 65.8%). However, disease activity data such as DAS28 components were similar. Mean DAS28 CRP values were significantly decreased at week 12 in both groups, and further decreasing were observed continuously (Fig. 1). However, disease activities were significantly lower in Naive group (p Conclusions This study demonstrated that the long term outcome of ABT therapy in clinical routine practice were comparable to that in clinical trials and useful as the first biologic agent for RA patients. It was the important data that adverse event leading to discontinuation was very low over three years in both group. Safety as well as efficacy is an important consideration when initiating intensive treatment, especially in patients with serious comorbidity. Our results suggest that ABT would be beneficial for patients who have complications with careful treatment. Disclosure of Interest M. Hanabayashi: None declared, N. Takahashi: None declared, H. Miyake: None declared, Y. Yokota: None declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, abbvie, Bristol-Myers Squibb, Pfizer, Janssen Pharmaceutical K.K. and UCB Japan Co. Ltd., N. Ishiguro Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, abbvie, Bristol-Myers Squibb, Pfizer, Janssen Pharmaceutical K.K. and UCB Japan Co. Ltd.

Background Abatacept (ABT), a selective co-stimulation modulator, is the first in a new class of biologic agents for the treatment of rheumatoid arthritis (RA) that inhibits T cell activation by binding to CD80/86, and modulating its interaction with CD28. Although some reports demonstrated that concomitant methotrexate (MTX) had little enhancing effect on short-term clinical efficacy of ABT [1,2], there have been only few long-term studies. Objectives We studied whether background MTX treatment enhanced the ABT efficacy after 24 weeks, by using data from Japanese multicenter registry system for RA patients using biological DMARDs. Methods All RA patients who underwent ABT treatment for at least 52 weeks (n=254) in Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Registry Study Group [2]) were enrolled in this study. Demographic data and the following parameters of disease activity were collected; tender joint count (TJC) and swollen joint count (SJC) on 28 joints, patient global assessment (VAS), ESR, and serum CRP and MMP-3 levels at baseline, 24 weeks, and 52 weeks. We compared these clinical data between the patients treated without concomitant MTX (ABT-mono, n=130) and those treated with concomitant MTX (ABT-MTX, n=124, mean MTX dose of 7.4 mg/week). The last observation carried forward (LOCF) method was used in each analysis. Results In the baseline characteristic data, the ABT-mono group had higher pulmonary comorbidity rate (21.5 vs 6.5%, p=0.001) compared to the ABT-MTX group while no other clinical parameters showed significant difference including the proportion of patients with previous biological DMARDs history (47.7 vs 47.6, p=0.986) or the all disease activity indices such as DAS28 (4.48 and 4.54). As shown in Fig. 1, top panels, the ABT-MTX group demonstrated statistically significant decreasing of DAS28 from 24 to 52 weeks while no difference in the ABT-mono group. We next studied the patients that still adhered on ABT therapy in spite of their poor clinical efficacy (moderate or high disease activity, DAS28-CRP >2.7) at 24 weeks. Logistic regression analysis identified the concomitant MTX therapy and female as independent predictors of DAS28 category improvement (e.g. high to moderate disease activity) from 24 to 52 weeks (Fig. 1, bottom panel). Conclusions Concomitant MTX therapy significantly decreased the disease activity after 24 weeks, while it seemed not to have enhancing effect on short-term clinical efficacy of ABT. It is true that the ABT efficacy is still significant even in the patients without MTX usage. However, it would be beneficial to use concomitant MTX in most of RA patients without serious comorbidity for MTX usage. References Arthritis Care Res. 2013;65:718. Mod Rheumatol. 2013;23:904. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2346

Background The treatment of RA has improved significantly over the past decade with the introduction of highly effective tumor necrosis factor inhibitors (TNFi). However, these drugs have little or no effect in about 30% of treated patients. In these cases, the disease-modifying antirheumatic drugs (DMARDs) must be switched. According to the European League Against Rheumatism recommendations, patients who do not respond to initial TNFi therapy should switch to a different TNFi or use a different class of biological DMARD (abatacept, rituximab or tocilizumab) [1]. While several studies have reported on switching from TNFi to other biologics [2, 3], no consensus exists on which drug should be chosen. Objectives The aim of this study was to compare the efficacy and retention rates of three biologics (abatacept, tocilizumab and etanercept) after switching from first-course anti-TNF monoclonal antibody therapy. Methods We performed a retrospective multicenter study of 89 patients who underwent second-course biologic therapy for 52 weeks after switching from first-course anti-TNF monoclonal antibody therapy in the Tsurumai Biologic Communication Registry (TBCR). Patients were divided into three groups based on the biologic they switched to: abatacept (n=25), tocilizumab (n=38) and etanercept (n=26). Changes in clinical parameters were examined at 0, 24, and 52 weeks after the switch. Disease activity was evaluated at each time point using the DAS28-CRP, as well as the CDAI, which included data from the above-mentioned disease parameters. Results Patients at baseline had a mean age of 58.7 years, mean disease duration of 9.8 years, and mean clinical disease activity index (CDAI) of 22.4. There was no significant difference between the three drugs, except in rheumatoid factor positivity. Retention rates for abatacept, tocilizumab and etanercept at 52 weeks were 72.0%, 89.5% and 84.6%, respectively (Fig. 1). The evaluation of CDAI indicated no significant difference at 52 weeks among the three drugs (Fig. 2). Discontinuation due to all unfavorable causes did not significantly differ among the three drugs in hazard ratio-based evaluations (Table 1). Conclusions This study is the first to compare the clinical efficacy of three different classes of biological DMARDs (abatacept, tocilizumab and etanercept) after the first-line anti-TNF agent using a multicenter registry system. Patients treated with abatacept, tocilizumab and etanercept achieved a high response rate with no significant differences in drug retention rates and clinical efficacy. These drugs offer good therapeutic options in patients with inadequate response to anti-TNF monoclonal antibodies. References Smolen JS, et al. Annals of the Rheumatic Diseases 2010;69:964-75. Leffers HC, et al. Annals of the Rheumatic Diseases 2011;70:1216-22. Hjardem E, et al. Annals of the Rheumatic Diseases 2007;66:1184-9. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1840

Background The 2010 EULAR Recommendations have been updated last year, abatacept (ABT) has become available as the first biologic agent for patients with RA (1). The long term efficacy and safety of ABT in patients with or without previous biologic therapy has been reported in clinical trials, but still uncertain in clinical routine practice. Objectives The aim of this study was to assess the 2-year outcomes of ABT therapy in biologic naive patients (Naive group) and patients failed to prior biologics (Switch group) in clinical routine practice. Methods All RA patients who were initiated ABT therapy from October 2010 through to October 2011 (n=152) at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communications Registry: TBCR group) were enrolled in this study. We compared disease activities using DAS28 CRP between Naive group (n=66) and Switch group (n=86). Furthermore, discontinuation due to inadequate responses (IRs) and adverse events (AEs) were evaluated. Results In the baseline characteristics data, there was no significant difference between Naive and Switch group, except for age (64.9 vs. 61.9 years old), disease duration (10.4 vs. 14.1 years) and swollen joint count (4.1 vs. 6.5). Disease activities were significantly decreased at week 12 in both groups, and further decreasing were observed continuously (Fig. 1). However, DAS28 CRP values were significantly lower in Naive group (p Conclusions This study demonstrated that the long term efficacy and safety of ABT in clinical routine practice was comparable to that in clinical trials. Interestingly, no adverse event leading to discontinuation was observed after week 24 except one patient. Safety as well as efficacy is an important consideration when initiating intensive treatment, especially in patients with serious comorbidity. Our results suggest that ABT would be beneficial for patients who have complications with careful treatment. References Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2013. Disclosure of Interest M. Hanabayashi: None declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer., N. Takahashi: None declared, D. Kida: None declared, K. Funahashi: None declared, S. Hirabara: None declared, S. Asai: None declared, Y. Yoshioka: None declared, N. Ishiguro Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer. DOI 10.1136/annrheumdis-2014-eular.2078

Background In the last decade, treatment with tumor necrosis factor (TNF) inhibitors has significantly improved the outcome in patients with rheumatoid arthritis (RA). Recent studies have highlighted drug immunogenicity as a mechanism behind treatment failure. Concomitant immunosupressors, such as methotrexate (MTX), can reduce the production of anti-drug anitibodies (ADA) which might reduce drug efficacy and result in drug discontinuation. Objectives We investigated the effect of concomitant use of MTX on the long-term adherence of etanercept and adalimumab. Methods All eligible patients were registered in the Tsurumai Biologics Communication Registry (TBCR), an RA research consortium that consists of Nagoya University Hospital and 12 affiliated institutes. As of September 2011, 2,176 RA patients treated with biologics are registered in this registry. Seven hundred ninety four RA patients previously unexposed to biological DMARDs were treated with etanercept (n=560) or adalimumab (n=234). Drug discontinuation rates were calculated by Kaplan-Meier method using the end-point of inefficacy or adverse events. Statistical difference between two groups was tested by Log-rank test. Statistical significance was defined as p-value Results Among the etanercept group, the discontinuation rate due to inefficacy were quite similar between the patients with concomitant MTX (n=385) and those without (n=175) (16.8 vs 14.8% at 3 years and 22.2 vs 24.5% at 6 years, p=0.936, Fig. 1a). Conversely among the adalimumab group, the patients with concomitant MTX demonstrated significantly lower discontinuation rate due to inefficacy (13.5 vs 36.2% at 3 years, p=0.014, Fig. 1c). The patients without MTX demonstrated significantly higher discontinuation rate due to adverse events both in the etanercept (p=0.011, Fig. 1b) and adalimumab group (p=0.016, Fig. 1d). The reason for this difference would have included the patients9 background complications for which they could not take MTX therapy. Unfortunately, such information was not available in the registry data. Conclusions It was quite interesting that the concomitant MTX usage did not improve the discontinuation rate due to inefficacy in the patients with etanercept therapy. Production of anti-drug antibodies (ADA) reduces the biological DMARDs effect that can be attenuated by concomitant methotrexate, which reduces ADA frequency. In the case of adalimumab, some previous reports demonstrated that the long-term clinical outcome is strongly dependent on the presence or absence of anti-adalimumab antibodies. On the other hand, some report showed that anti-etanercept antibody is hardly detected. Our current data clearly support these previous data that showed less immunogenicity of etanercept. Thus, we would conclude that the drug immunogenicity should be considered especially for the patients that cannot take concomitant MTX. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1422

Background EULAR recommends that all biologics DMARDs should be used preferentially in combination with methotrexate (MTX) in rheumatoid arthritis (RA) patients. The TEMPO study and the JESMR study showed that combination therapy with Etanercept (ETN) plus MTX was significantly superior to ETN alone in inhibiting radiographic progression of the hands, wrists, and forefeet [1, 2]. However, it is still unclear whether concomitant MTX affect inhibiting progression of large joint destruction in RA patients treated with ETN. Total joint replacement is a common procedure for damaged large joint, and it is the essential marker of severe joint destruction in RA patients [3]. Objectives The aim of this study was to investigate the effect of concomitant use of MTX on the incidence of large joint replacement surgery in RA patients treated with ETN. Methods A retrospective multicenter study was performed by using Tsurumai Biologics Communication Registry (TBCR), which consisted of patients who were starting biologic treatments and included baseline characteristics. Of 652 RA patients treated with ETN, 42 patients underwent 58 total joint replacement (34 TKA, 19 THA, 3 TEA, 1 TAA and 1 TSA) during treatment with ETN. The incident rate of total joint replacement was determined by the Kaplan-Meier method. Statistical different was tested by Log-rank test. To identify risk factors for incidence of total joint replacement, impact of baseline clinical variables were analyzed by using Cox proportional hazards regression analysis. Results Patients were predominantly female (83.9%), and had a mean age of 59 years, disease duration of 10.9 years and DAS28-ESR of 5.4 at initiation of ETN. MTX was concomitantly used with 70.4% of the patients. Mean time between initiation of ETN and total joint replacement was 1.5 years. The incident rate of total joint replacement for the patients with concomitant MTX was significantly lower than that for the patients without concomitant MTX (6.7 vs 12.3% at 5years, p=0.032, Figure1). Multivariate analysis identified no concomitant MTX use and age at initiation of ETN as the independent risk factors for incidence of total joint replacement (Table 1). Radiographic data was not available in the registry data though the existing joint damage at baseline would affect the need for total joint replacement. Conclusions This study demonstrated that combination therapy with ETN plus MTX was superior to ETN alone in reducing the incidence of large joint replacement surgery. Our data support the EULAR recommendation. ETN should be used preferentially in combination with MTX to inhibit progression of large joint destruction as well as hand and foot joint destruction. References van der Heijde D. Arthritis Rheum 2006; 54: 1063-74 Hideto Kameda. J Rheumatol 2011; 38: 1585-92 Wolfe F. Arthritis Rheum 1998; 41: 1072-82 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1502

Background After demonstration of effectiveness of anti-tumor necrosis factor (TNF) agents in patients with rheumatoid arthritis (RA), their use has become common practice in treating patients not responding to classical disease modifying anti-rheumatic drugs (DMARDs). Objectives In this paper, we studied the long-term clinical outcome of infliximab, which is first biological DMARD for RA in Japan, to demonstrate the “real-world” data using our registry system. Methods All eligible patients were registered in the Tsurumai Biologics Communication Registry (TBCR), an RA research consortium that consists of Nagoya University Hospital and 12 affiliated institutes. As of September 2011, 2,176 RA patients treated with biologics are registered in this registry system. Four hundred forty seven RA patients previously unexposed to biological DMARDs were treated with infliximab (IFX). Drug retention rates were calculated by Kaplan-Meier method using endpoint of inefficacy or adverse events. Results As baseline characteristics, mean age was 56.6 years, disease duration was 14.9 years, proportion of patients with methotrexate was 99.6%, MTX dose was 7.2 mg/week, proportion of patients with prednisolone (PSL) was 76.1%, PSL dose was 5.2 mg, serum C-reactive protein was 3.8 mg/dL, and DAS28 was 5.7. IFX retention rate was 67.5% at 1 year, 31.0% at 5 years, and 22.5% at 8 years (Fig. 1a). IFX discontinuation rate due to inefficacy was 58.1% (Fig. 1b). Primary inefficacy was seen in 6.9% and secondary inefficacy was seen in 27.1% of patients. Discontinuation rate due to adverse events was 42.7% at 8 years (Fig. 1c). Most frequent adverse events resulted in IFX discontinuation was pulmonary complication (9.8%) including interstitial pneumonia (IP, 2.5%), bacterial pneumonia (4.3%), pulmonary tuberculosis (1.1%), pneumocystis pneumonia (0.7%), and organizing pneumonia (0.4%). The second most frequent was infusion reaction seen in 7.8%. The incidence of malignant neoplasm was seen in 1.8%. Conclusions We observed quite high discontinuation rate due to secondary inefficacy. This is probably dependent on the relatively low MTX dose, because of the Japanese regulation of public health insurance coverage. We are convinced of improved discontinuation rate if only with higher dose of concomitant MTX, which would reduce the production of anti-IFX antibodies resulting in secondary inefficacy and infusion reaction. It was the important data that the most frequent adverse events resulting in discontinuation was pulmonary complications. Putting all our results together, we would suggest that the most suitable patients for IFX treatment, expecting long-tern adherence, would be ones using sufficient dosage of concomitant MTX treatment and do not have baseline comorbidity of pulmonary diseases. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1420

Background Now, predictive factors at baseline for the good outcome of treatment with biologics are very important not to waste time to treatment goal “remission”. Objectives The aims of this study are to clarify the characteristics of the patients enrolled in this observational cohort and to identify the predictive factors at baseline for achievement of the remission in treatment with tocilizumab (TCZ), in daily practice setting with background of limited dose of MTX (5.1) at week 52 were follows: concomitant MTX [OR 2.63 (1.16-6.29)] and less structural damage (Steinbrocker stage I+II)[OR 1.44 (1.55-9.69)]. Interestingly, no significant baseline factors were found in the patients with moderate/low disease activity (DAS28 ≤5.1). However, changes in disease activity and its component showed that patients with moderate/low disease activity and those who did not achieve remission showed no remarkable improvement in patient general assessment (VAS) and tender joint count ([Fig. 1B][1]), compared to patients who had high disease activity and who did not achieve remission ([Fig. 1A][1]) Thus, structural damage could be more influential towards disease activity than inflammation in patients with moderate/low disease activity and those who did not achieve remission. ![Figure 1][2] Figure 1 Conclusions Even low dose of MTX could plays critical roles on RA treatment during TCZ treatment for the patients with high disease activity. The information with background of limited dose of MTX should be important for clinical practice.We should consider structural damage more carefully when the patients with moderate/low disease activity as well as with high disease activity were treated with TCZ to be achieved remission. Disclosure of Interest T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer, N. Takahashi: None declared, K. Funahashi: None declared, S. Asai: None declared, S. Hirabara: None declared, M. Hanabayashi: None declared, Y. Yoshioka: None declared, Y. Yabe: None declared, N. Ishiguro Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer DOI 10.1136/annrheumdis-2014-eular.1710 [1]: #F1 [2]: pending:yes

Background Tocilizumab (TCZ) is the first humanised monoclonal antibody that targets and inhibits the human interleukin-6 receptor. The ACT-RAY study proved the clinical efficacy and safety of adding TCZ to MTX versus switching from MTX to TCZ monotherapy in biologic-naive adult patients with moderate to severe active rheumatoid arthritis (RA). [1]. But the clinical long term outcome is not clear. Objectives To evaluate the continuity and effectiveness of TCZ with/without MTX by using multi-center registry for the treatment of RA with biologics in Japan (Tsurumai Biologics Communication Registry; TBCR) [2]. Methods 302 RA patients treated with TCZ for at least 24 months in Nagoya University Hospital and 12 affiliated institutes (TBCR Study Group) were enrolled in this study.155 cases treated with MTX at the baseline (MTX+ group),147 case did not take MTX at the baseline (MTX- group). Difference in baseline characteristics was summarized in [Table 1][1]. Drug retention rate of both groups was examined using Kaplan-Meier survival analysis. DAS28ESR was compared between these two groups by unpaired t- test at 0, 6, 12, 24 months. The last observation carried forward (LOCF) method was used in each analysis. Results In MTX+ group, 12 cases (7.7%) discontinued TCZ therapy because of inadequate response (IR), 12 cases (7.7%) stopped TCZ infusion because of adverse events (AEs), 8 (5.1%) cases stopped due to other reasons. In MTX- group, 13 cases (8.8%) discontinued TCZ therapy because of IR, 18 cases (12.2%) stopped TCZ infusion because of AEs, 11 (7.5%) cases stopped due to other reasons. DAS28ESR of MTX+ group at 0, 6, 12, 24 months was 5.4, 2.9, 2.7, and 2.7, respectively. That of MTX- group was 5.8, 3.3, 3.3, and 3.4, respectively. Although disease activity based on DAS28ESR was not significantly different between two groups at 0, 6 months, it is significantly different at 12, 24 months (p

Background Abatacept (ABT), a selective co-stimulation modulator, is the first in a new class of biologic agents for the treatment of rheumatoid arthritis (RA) that inhibits T cell activation by binding to CD80/86, and modulating its interaction with CD28. The AMPLE trial demonstrated that clinical efficacy of ABT was equivalent to adalimumab [1]. However, some physicians make assertions that the treatment response of ABT seems to be slower than other class biological DMARDs and we should wait longer periods before deciding whether to continue ABT. Objectives We studied the appropriate periods for deciding to continue or discontinue ABT, by using data from the Japanese multicenter registry system for RA patients using biological DMARDs. Methods All RA patients who underwent ABT treatment for at least 52 weeks (n=254) in Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Registry Study Group [2]) were enrolled in this study. Demographic data and the following parameters of disease activity were collected; tender joint count (TJC) and swollen joint count (SJC) on 28 joints, patient global assessment (VAS), ESR, and serum CRP and MMP-3 levels at baseline, 4, 12, 24, and 52 weeks. The last observation carried forward (LOCF) method was used in each analysis. We used a conventional receiver-operating-characteristic (ROC) curve to analyze DAS28 scores at each time point in order to determine the cutoff points that yielded the highest combined sensitivity and specificity with respect to distinguish patients achieved low disease activity (LDA, DAS28-CRP Results In the baseline characteristic data, mean age was 64.5 years, mean disease duration was 11.3 years, and proportion of patients with previous biological DMARDs history was 48.0% and with concomitant MTX usage was 48.8%. We analyzed DAS28 scores at baseline, 4, 12, and 24 weeks. As shown in Fig. 1 left panel, area-under-curve (AUC) was lowest in baseline DAS28 score and highest in 12 and 24 weeks. We chose the shorter time point, 12 weeks, for further study. The cutoff point of DAS28 score at 12 weeks that gave the maximal sensitivity (81%) and specificity (81%) was 3.3. Seventy seven percent of the patients with lower than 3.3 of DAS28-CRP at 12 weeks achieved LDA at 52 weeks (Fig. 1 right panel). Logistic regression analysis identified the previous biological DMARDs history and DAS28-CRP score ( Conclusions According to the difference of AUC score, 4 weeks would be too short and 12 weeks would be long enough to predict low disease activity at 52 weeks in the RA patients treated with ABT. Since we usually decide whether to continue anti-TNF agents at 12 weeks, the treatment response of ABT seemed to be equivalent to that of anti-TNF agents as shown in the AMPLE trial. We would suggest that we can decide to discontinue ABT and switch to other agents if the treatment response is insufficient at 12 weeks. References Arthritis Rheum. 2013;65:28. Mod Rheumatol. 2013;23:904. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2349

Background With the advent of methotrexate and biological disease-modifying antirheumatic drugs, clinical remission has been a realistic goal in rheumatoid arthritis (RA). In 2011 ACR/EULAR Boolean-based definition of remission in RA, patient global assessment (PGA) is often the limiting factor for reaching remission. 1 The main determinants for the PGA are pain, function, and number of swollen joints. 2 Physical function will affair clinical remission. Given the tight correlation between physical function and loss of social and economic opportunities, 3 as well as clinical remission, functional remission is also an important goal. Objectives To clarify the characteristics of Health Assessment Questionnaire (HAQ) and its items from the point of view of disease activity and disease duration of RA. Methods 512 RA patients at Nagoya University Hospital were enrolled in this study. Physical function was assessed using HAQ, disease activity DAS28-CRP, PGA 0-10 visual analog scale. Pearson correlation coefficient, chi square test, and unpaired t-test were used for static analysis. Results Patients were primarily women (81.4%). Mean age was 60.3±14.0 years, disease duration 13.0±10.4 years, HAQ-DI 0.67±0.75, and DAS28-CRP 2.37±1.02. HAQ-DI was getting worse in correlation with disease activity (r=0.452) (Fig. 1), and disease duration (r=0.446) (Fig. 2). In the early stage of RA (duration Considering the questionnaires by, #10 Hygiene, #17 Grip, and #20 Activities had stronger correlation with disease activity. #1 Dressing & Grooming, #5 Eating, and #7 Eating had stronger correlation with disease duration. PGA had a most strong correlation with the HAQ-DI in the components of the DAS28-CRP (r=0.395). Of the patients who are in functional remission (HAQ-DI Conclusions Physical function was associated with disease activity, especially in the early stage. In order to prevent the progression of dysfunction or to achieve functional remission, reducing disease activity is important. Some questionnaires correlated stronger with disease duration rather than disease activity, which suggests that reducing only disease activity is not enough. In addition, HAQ-DI is also associated with PGA. This study suggests that improving HAQ-DI by such as surgery and rehabilitation, leads to not only functional remission but also clinical remission through improving PGA. References Studenic P, Smolen JS, Aletaha D. Near Misses of ACR/EULAR criteria for remission: effects of patient global assessment in Boolean an index-based definitions. Ann Rheum Dis 2012;71:1702-1705 Studenic P, Radnner H, Smolen JS, Aletaha D. Discrepancies between patients and physicians in their perceptions of rheumatoid disease activity. Arthritis Rheum 2012;64:2814-2823 Strand V, Khanna D. The impact of rheumatoid arthritis and treatment on patients9 lifes. Clin Exp Rheumatol 2010;28:S32-40 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2079

Background The 2008 American College of Rheumatology Recommendations has been updated last year, abatacept (ABT) has become available as the first biologic agent for patients with established RA[1][1]. The efficacy and safety of ABT in biologic naive patients has been reported in clinical trials, but still uncertain in clinical practice. Objectives We studied the clinical outcome of ABT treatment for 52 weeks in patients without previous biologic history (Naive group) and with previous biologic treatment (Switch group). We assessed whether the history of previous biologic treatment had any impact on the ABT clinical efficacy in RA. Methods All RA patients who underwent ABT treatment for longer than 52 weeks (n=156) at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communications registry : TBCR study group) were enrolled in this study. We compared disease activities using DAS28 CRP between Naive group (n=71) and Switch group (n=85). Furthermore, EULAR response criteria and drug retention rate at 52 weeks were evaluated. The last observation carried forward (LOCF) method was used in each analysis. Results In the baseline characteristics data, there was no significant difference between Naive and Switch group, except for age (65.1 and 61.9 years old), disease duration (10.4 and 12.6 years) and prednisolone user (38.5 and 61.5%). Disease activities were significantly decreased at 4 weeks in both groups, and further decreasing were observed continuously ([Fig. 1][2]). At 52 weeks, the percentage of the patients who achieved low disease activity (DAS28 < 2.7) in Naive group (47.8%) was apparently higher than that in Switch group (23.8%) ([Fig.2][2]). EULAR response rate was 75.3% in Naive group (good 36.2%, moderate 39.1%), while 47.5% in Switch group (good 17.5%, moderate 30.0%). Drug retention rate at 52 weeks was 81.7% in Naive group and 71.8% in Switch group ([Fig 3][2]). ![Figure][3] Conclusions Although the clinical efficacy of ABT was demonstrated in patients with the history of biologics treatment, the responsiveness to ABT was superior in the biologic naive patients. Our data suggest that ABT is useful in biologic naive patients in clinical practice. References 1. Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis care & research. 2012;64:625-39. Disclosure of Interest M. Hanabayashi: None Declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer., N. Takahashi: None Declared, K. Funahashi: None Declared, D. Kato: None Declared, Y. Hattori: None Declared, N. Ishiguro Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer. [1]: #p-7 [2]: #F1 [3]: pending:yes

Background MMP-3 is an enzyme produced by synoviocytes, and is a marker of synovitis that gives a more direct indication of actual joint destruction than either C-reactive protein (CRP)in patients with rheumatoid arthritis (RA). Objectives Our aim in this study is to investigate the impact of the trend of MMP-3 and CRP during the treatment Adalimumub (ADA) and Abatacept (ABT) in the early stage of RA patients. Methods Among 295 patients with active RA (DAS28-CRP≥2.7) who were recruited in the multicenter study group (Tsurumai Biologics Communication Registry; TBCR), 154 patients were received ADA (40mg subcutaneously every other week) and 141 patients were received ABT therapy (500mg for 100 kg infusion at week 0, 2, 4 and every 4 weeks). DAS28-CRP remission (DAS28-CRP Results While there was significant baseline difference in age, methotrexate (MTX) use between the two groups, there was no significant baseline difference in serum MMP-3 and CRP levels between the two groups (Table). Serum MMP-3 and CRP levels decreased promptly at 4 weeks. The change in serum MMP-3 levels at 4, 12, and 24 weeks was significantly greater in the ADA group than in the ABT group (Fig. 1). However, the change in CRP levels at 4, 12, and 24 weeks had no significant deference between the two groups (Fig. 2). Similarly the % change in serum MMP-3 levels at 4, 12, and 24 weeks was significantly greater in the ADA group than in the ABT group (Fig. 3) and there was no difference in the % change in CRP levels at 4, 12, and 24 weeks between the two groups (Fig. 4). Image/graph Conclusions ADA showed improvements in serum MMP-3 levels from an early stage in 24 weeks in a comparison with ABT. ADA can suppress synovitis and therefore the progression of joint destruction by strongly inhibiting MMP-3 when it is administered from an early stage. Disclosure of Interest : Y. Hattori: None Declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer, N. Takahashi: None Declared, K. Funahashi: None Declared, D. Kato: None Declared, M. Hanabayashi: None Declared, N. Ishiguro Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer

Background Recently, in the RA treatment, clinical remission had been a realistic target by methotrexate and biologics. Moreover, strict remission criteria such as Boolean index or SDAI Objectives The aim of this study was evaluating the effect of intra-articular steroid injection with clinical measure and ultrasonography focused on its efficacy and sustainability in the RA patients their internal treatment is considered to be enough to control their disease activity. Methods 16cases of RA patients who received intra-articular steroid injection to their small number of swollen joints in our clinic from April 2009 to September 2012 were recruited. After intra-articular injection of triamcinolone acetonide and lidocaine to power doppler (PD) positive swollen joint, durability of effect were evaluated with ultrasonography (US), and disease activity were evaluated with composite measures and biochemical markers in every 4 to 8 weeks ambulatory visits. Results Injected joint were knee:1, shoulder:1, elbow:2, wrist:5, MCP:3 and PIP:4 respectively. Mean followed up period was 11.1 (2.5-40) months. The characteristic data is shown in Table1. After injection, remission and LDA rate was significantly increased in each composite measures as showed in Figure1. CRP titer was also significantly improved from 0.32±0.33 to 0.09±0.10mg/dl. Gray scale grading and PD signal grading were significantly improved and preserved during observation period. In 2cases, PD signal were relapsed at 4 month after injection, but stayed in Grade1 without additional treatment. Serum MMP-3 level was significantly decreased by injection, and it was preserved until last observation as showed in Figure2. Image/graph Conclusions Frequent intra-articular steroid injection should be avoided because of its harmful effect on joint. But for the RA patients achieved clinical remission or LDA, this double edged sword might be a useful application to achieve and maintain strict remission state. And if internal treatment succeeded to keep the disease activity at low, single time intra-articular injection may provide lasting swelling free joint. Disclosure of Interest D. Kato: None Declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer., K. Funahashi: None Declared, T. Takemoto: None Declared, Y. Yoshioka: None Declared, T. Watanabe: None Declared, N. Takahashi: None Declared, Y. Hattori: None Declared, M. Hanabayashi: None Declared, N. Ishiguro Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma, Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer.