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Objectives: To compare the radiographic and clinical effects of 25 versus 10 mg twice-weekly (BIW) etanercept over 52 weeks in Japanese patients with active rheumatoid arthritis (RA). Methods: This was a post-hoc analysis of a Phase 3 study where Japanese patients with active RA were randomized to receive BIW etanercept 25 mg (n = 182), etanercept 10 mg (n = 192), or methotrexate (n = 176) for 52 weeks (NCT00445770). This analysis included assessments of week-24 and week-52 disease activity, week-52 radiographic progression, and the relationship between baseline characteristics and week 52 clinical outcomes with clinically relevant radiographic progression (CRRP) at week 52. Results: At week 52, there were no significant differences between 25 and 10 mg etanercept in terms of achieving low disease activity or remission. CRRP was observed in 36% and 32% of patients in the 10 and 25 mg groups, respectively. Predictor analysis suggested that worse background disease status, treatment with methotrexate rather than etanercept, and poorer clinical outcomes at week 52 were associated with CRRP. Conclusions: The 25 mg BIW etanercept dosage does not appear to be significantly more efficacious than 10 mg in Japanese patients with RA. Further studies evaluating the optimal etanercept dosing regimen in this patient population may be merited. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety of tacrolimus in adult patients with rheumatoid arthritis (RA) by using the GRADE approach. Methods: We searched PubMed, Japana Centra Revuo Medicina Web (Ichu-shi web), and the Cochrane Database of Systematic Reviews. Articles fulfilling the predefined inclusion criteria were appraised and used for meta-analysis. The primary outcomes were American College of Rheumatology 20 (ACR20) and serum creatinine elevation. Other outcomes included ACR50, ACR70, changes in C-reactive protein, modified Health Assessment Questionnaire Disability Index, gastrointestinal disorders, metabolic and nutritional disorders, and infections and infestations. Results: We identified five randomized controlled studies, four of which compared tacrolimus to placebo and were included in the meta-analysis. The risk ratio of ACR20 achievement was 1.71 (95% confidence interval [CI] 1.20 -2.42) for 1 -2mg/day and 2.30 (95% CI 1.79 -2.96) for 3 mg/day. The risk ratio of creatinine elevation was 1.95 (95% CI 1.18 -3.23) for 1 -2mg/day and 3.81 (95% CI 2.43 -5.99) for 3 mg/day. Conclusion: Tacrolimus is effective with acceptable safety in the management of RA. [ABSTRACT FROM AUTHOR]

Objectives: To elucidate the epidemiological characteristics of patients with rheumatoid arthritis (RA) in Japan using data from the Comprehensive Survey of Living Conditions, a nationwide questionnaire survey conducted in 2016.Methods: In total, 222,365 men and 245,251 women aged ≥16 years were included in the study. RA patients were defined as those who reported 'currently receiving treatment for RA at hospitals, clinics, or a facility for Japanese traditional massage, acupuncture, moxibustion, or judo-orthopedics.' The number of RA patients was estimated from the age-specific prevalence and total Japanese population in 2016. Further, the prevalence of individuals experiencing difficulties in activities of daily living due to health problems and those with mental distress as evaluated by K6 Scale was examined.Results: The estimated number and prevalence of RA in Japan with 95% confidence interval was 822 (768-880) thousand and 0.75% (0.70-0.80%). The population peaked in the late 60s, and the prevalence continued increasing until the early 80s, regardless of sex. Compared with non-RA participants, RA patients were more likely to experience difficulties in activities and to be distressed.Conclusion: High prevalence of RA in older age and mental and physical burden among RA patients were confirmed. [ABSTRACT FROM AUTHOR]

Objectives: To identify predictive factors for remission by tocilizumab monotherapy in rheumatoid arthritis (RA) patients. Methods: This is a post hoc analysis of the SURPRISE study, a 2-year randomized, controlled study comparing the efficacy of tocilizumab with (ADD-ON) and without methotrexate (SWITCH). The primary endpoint was DAS28-ESR remission (<2.6) at week 24. The change in modified total Sharp score from baseline to week 52 (ΔmTSS/year) was also assessed as an endpoint. The effect of clinical parameters at baseline on remission was estimated by logistic regression analysis. Results: In SWITCH (n = 96), CRP, SAA, RF, and DAS28 at baseline showed predictive value for DAS28 remission in unadjusted analysis. Adjusted analysis confirmed SAA and DAS28 as predictive factors, with SAA having the highest value (ROC-AUC = 0.731). Furthermore, structural remission (ΔmTSS/year ≤0.5) rate was significantly higher in patients with SAA of <50.0 µg/mL than other patients. In contrast, in ADD-ON (n = 98), only DAS28 showed predictive value for DAS28 remission. In patients with SAA <50.0 lg/mL, both DAS28 remission and structural remission rate were comparable between SWITCH and ADD-ON. Conclusion: RA patients with low SAA levels at baseline may benefit similarly from tocilizumab with and without methotrexate. Trial registration number: NCT01120366. [ABSTRACT FROM AUTHOR]

Objectives: Compare outcomes with methotrexate (MTX) or etanercept (ETN) monotherapy in Japanese patients with active rheumatoid arthritis (RA) who were MTX-naïve or with intolerance or inadequate response to prior MTX (MTX-IR). Methods: Post hoc analysis of a phase 3 study comparing MTX, ETN 10 mg twice weekly, and ETN 25 mg twice weekly in Japanese patients with RA. Disease activity was evaluated using American College of Rheumatology (ACR) scores and 28-joint Disease Activity Score (DAS28), radiographic progression evaluated using van der Heijde's modified Total Sharp Score (mTSS), and functional status evaluated using Health Assessment Questionnaire Disability Index (HAQ-DI). Results: Among MTX-naïve and MTX-IR patients, greater proportions of those randomized to either ETN group achieved ACR20, ACR50, ACR70, DAS28 ≤3.2 or <2.6, clinically relevant inhibition of mTSS changes, and reductions in HAQ-DI compared with MTX at the majority of time points. There were very few clinically meaningful differences between ETN groups for any of the variables evaluated. Conclusion: ETN monotherapy was more effective than MTX in both MTX-naïve and MTX-IR patients, with very few clinically meaningful differences between ETN 10 mg and ETN 25 mg when given twice weekly. The relative benefits of ETN were greater in MTX-naïve patients than MTX-IR patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk of hospitalized infection (HI), cardiovascular disease (CVD), stroke, and fracture in rheumatoid arthritis (RA) patients compared with non-RA patients using the Japanese health insurance database. Method: Among individuals aged -18 years, RA cases were defined to have one RA diagnostic code and receiving -1 disease-modifying antirheumatic drug between 2005 and 2013 (n¼6,712). Age-, sex-, calendar year of the observation start-, and observation length-matched non-RA cases were selected at 1:5 (n¼33,560). Hazard ratios (HRs) were calculated using the time-dependent Cox regression analysis. Results: Median age of the patients was 52.0 years. The incidence rates of HI, CVD, and fracture in the RA group were 2.42/100 person-years (PY), 4.94/1,000 PY, and 10.59/1,000 PY. The crude incidence rate ratios (95% CI) (RA vs. non-RA) for HI, CVD, and fracture were 2.47 (2.20-2.77), 1.89 (1.49-2.41), and 3.35 (2.80-4.02). The adjusted HR (95% CI) (RA vs. non-RA) was significantly elevated (HI, 1.74 [1.52-1.99], CVD, 1.38 [1.04-1.85], and fracture, 1.88 (1.54-2.31)]. Conclusion: The relatively young RA population had significantly higher risks of these complications than the non-RA, indicating importance of prevention of them even at young ages in clinical settings. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the real-world safety and effectiveness of etanercept (ETN) in Japanese patients with rheumatoid arthritis. Methods: This postmarketing surveillance study (NCT00503139) assessed the safety and effectiveness of ETN treatment over 3 and 2 years (from June 2007 to September 2011), respectively. Safety was evaluated by occurrence and seriousness of adverse drug reactions (ADRs), and of adverse events (AEs) for malignancies. Effectiveness was assessed using the Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate (ESR) with four variables (swollen and tender joint counts, ESR, and patient global assessment; DAS28-4/ESR). Treatment was considered effective if patients had a good/moderate response by the European League Against Rheumatism response criteria. Results: ADRs occurred in 256/675 (37.9%) patients, the most common being injection site reactions (4.4%) and nasopharyngitis (3.3%). Serious ADRs occurred in 60/675 (8.9%) patients, the most frequent being pneumonia (1.2%). The incident rate of malignancies (AEs) was 1.06 per 100 patient-years. Mean baseline DAS28-4/ESR for the 581 patients included in effectiveness analysis was 5.42, which decreased to 3.32 at 2 years. Eighty-two percent of patients achieved a moderate/good response at 2 years. Conclusion: Long-term ETN treatment safety and effectiveness were sustained over 3 and 2 years, respectively. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the safety and efficacy of golimumab through week 120 in Japanese patients with active rheumatoid arthritis (RA) previously treated with DMARDs. Methods: Japanese patients with active RA despite prior DMARDs were randomized to placebo (Group 1, n = 105), golimumab 50 mg (Group 2, n = 101), or golimumab 100 mg (Group 3, n = 102). At week 16, Group 1 patients crossed over to golimumab 50mg; after week 52, a one-time golimumab dose reduction from 100 to 50 mg was permitted. Assessments included ACR20/50/70 responses and good/moderate DAS28-ESR responses. Radiographic progression was assessed with the van der Heijde-modified Sharp (vdH-S) score. Safety and efficacy were assessed through week 120. Results: ACR20 response rates at week 52 in Group 1, Group 2, and Group 3 were 70.6%, 71.4%, and 81.9%, respectively, and maintained through week 104 (87.2%, 85.1%, 88.9%, respectively) and week 120 (86.1%, 87.0%, 89.5%, respectively). Similar trends were observed for ACR50, ACR 70, and DAS28-ESR. Median change in total vdH-S at weeks 52, 104, and 120 ranged from 0.0 to 1.5 across treatment groups. Through week 120, 93.8%/97.1% had an AE with golimumab 50 mg/100 mg, respectively, and 19.7%/11.8% had an SAE. Infections were the most common AE. Conclusion: Clinical response to golimumab 50 mg and 100 mg was maintained over 2 years in Japanese patients with active RA despite prior DMARDs. [ABSTRACT FROM AUTHOR]

Objective: Patients' values and preferences are among the key factors that determine the strength of recommendations presented in clinical practice guidelines (CPG). The aim of this study was to summarize the integration process for patients' perceptions into the development of CPG for rheumatoid arthritis (RA) management in Japan. Methods: We used a mixed-methods approach. Questionnaires that could be self-administered were mailed to 2222 RA patients randomly selected from the Japan Rheumatism Friendship Association (JRFA) membership list that was age- and prefecture-stratified. A focus group with five JRFA executive members was formed to verify the results of the questionnaire. Results: A total of 1470 patients aged 20-79 years old returned the questionnaire. Analysis of the questionnaire data revealed that the topics selected by the CPG task force met the patients' needs. The focus group participants showed reluctance to use the term 'preference' because patients would not want to take any medications but would have to take them out of necessity. Conclusions: We confirmed that the new CPG successfully addressed clinical issues that were important to both rheumatologists and patients. Clinicians should understand patients' reluctance to take medications and explain the role of each medication well to increase adherence. [ABSTRACT FROM AUTHOR]

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

Objectives: To investigate and compare the risk for malignancy in rheumatoid arthritis (RA) patients treated with biologics in Japan to the general population. Methods: Data for 14,440 patients from 335 institutions who were given infliximab, etanercept, adalimumab, golimumab, tocilizumab, or abatacept were retrieved from the SafEty of biologics in Clinical Use in Japanese patients with RhEumatoid arthritis (SECURE) database. Results: We identified 333 incidents of malignancies in 320 patients during 49,320 patient-years (PY). The age- and sex-standardized incidence rate (ASR) (95% confidence interval [CI]) for overall malignancy of the SECURE cohort was 313.9/105 PY (271.4-361.3), and the standardized incidence rate ratio (SIR) (95% CI) was 0.745 (0.667-0.826). The ASR was decreased compared to the estimated incidence rate of malignancies in the Japanese general population (462.4/105 PY). The SIRs for site-specific nonhematopoietic malignancies of the SECURE cohort were not significantly elevated compared to the Japanese general population. A significant increase of SIR for malignant lymphoma (6.183, 95% CI, 4.809-7.643) was found in the SECURE cohort, similar to or slightly higher than the SIR previously reported from Japanese cohorts for RA patients. Conclusions: Continued vigilance with larger numbers of patients, longer observation periods, and inclusion of different biologics are recommended. [ABSTRACT FROM AUTHOR]

Objective: To reveal any association between rheumatoid arthritis (RA) and cardiovascular comorbidities using a Japanese health insurance database. Method: This population-based cross-sectional study was conducted using health insurance data provided by the Japan Medical Data Center Co., Ltd. We identified 2762 RA subjects having RA diagnostic codes (ICD10 codes; M05, M060, M062-63, M068-069) with at least two physician visits more than two months apart between June 2011 and May 2012 (RA group, n=2762). We selected age- (±5 years), sex-, and study period-matched non-RA subjects (non-RA group, n=27,620). We compared the prevalence of cardiovascular and related comorbidities (ischemic heart diseases [IHD], cerebral infarction, hypertension [HT], dyslipidemia [DL], and diabetes mellitus [DM]) between these groups and investigated the association between RA and cardiovascular comorbidities using a conditional logistic regression analysis. Results: The prevalence of all the investigated comorbidities in the RA group was significantly higher compared to the non-RA group. Odds ratios [95% confidence interval] of RA for IHD and cerebral infarction were 2.0 [1.5-2.5] and 3.1 [2.2-4.2] respectively, after adjusting for HT, DL, and DM. Conclusions: This study revealed for the first time in the Japanese population that RA was significantly associated with cardiovascular comorbidities. [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Methods: Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200mg every 2 weeks (Q2W) groups starting with LD (400mg Weeks 0/2/4; LD group; J-RAPID: n=82, HIKARI: n=116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n=61, HIKARI: n=99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. Results: In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patientyears]). Conclusions: Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and efficacy of golimumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA). Methods: Japanese patients with active RA despite MTX were randomized to placebo + MTX (Group 1, n=88), golimumab 50mg+ MTX (Group 2, n=86), or golimumab 100mg+ MTX (Group 3, n=87). Patients with520% improvement in swollen/tender joint counts entered early escape at week 16. At week 24, all remaining placebo patients crossed over to golimumab 50 mg. Efficacy assessments included ACR20, DAS28-ESR, and HAQ-DI. Radiographic progression was assessed with the van der Heijde-modified Sharp (vdH-S) score. Results: ACR20 response rates in Group 1, Group 2, and Group 3 were 67.9, 86.1, and 82.4%, respectively, at week 52 and were maintained through week 104 (87.1, 94.0, and 88.7%) and week 156 (97.1, 94.1, and 89.5%). Proportions of patients with good/moderate DAS28-ESR response or clinically meaningful improvement in HAQ-DI were also maintained through week 156. The majority of patients did not experience radiographic progression through week 156. Among 257 golimumab-treated patients, 251 (97.7%) had -1 AE; 54 (21.0%) had -1 serious AE through week 156. Infections were the most common type of AE. Conclusions: Response to golimumab + MTX was maintained over 3 years in Japanese patients with active RA despite MTX. Safety results were consistent with the known safety profile of golimumab. [ABSTRACT FROM AUTHOR]

Objectives: To assess the influence of golimumab dosage and disease activity on joint destruction in patients with active rheumatoid arthritis (RA) in the GO-FORTH study. Methods: Efficacy was compared among groups given basal methotrexate plus placebo, golimumab (50 mg), or golimumab (100 mg) with stratification by high (HDA) or moderate (MDA) baseline disease activity and by high or low baseline C-reactive protein (CRP). Results: Among HDA or high CRP patients, the mean change of the total Sharp score was 3.48 and 3.41 in the placebo group, 1.94 and 2.71 in the 50mg group, and 0.39 and 1.15 in the 100mg group, respectively. The percentage of progression-free patients with HDA or high CRP was 40.4% and 40.0%, 43.1% and 38.2%, and 69.8% and 61.5%, respectively. Among MDA or low CRP patients, both golimumab doses showed similar prevention of joint destruction. Among HDA or high CRP patients, a shorter disease duration and higher TSS/disease duration ratio were associated with joint destruction. Conclusion: Both doses of golimumab (50 or 100 mg) prevented joint destruction in MDA or low CRP patients, but 100mg was better for HDA or high CRP patients with a shorter disease duration or higher TSS/disease duration ratio. [ABSTRACT FROM AUTHOR]

Objectives. To describe the process of collecting and evaluating evidence for treating rheumatoid arthritis (RA) for developing clinical practice guidelines (CPGs) for rheumatologists in Japan. Methods. The task force comprised rheumatologists, epidemiologists, health economists, and patients. First, the critical outcomes were determined according to a three-round Delphi method, and eight topics with 88 clinical questions (CQs) were formulated. A systematic review of CQs was conducted using the Cochran Database of Systematic Reviews, MEDLINE, and Japana Centra Revvo Medicina (2003 - 2012). A questionnaire survey and focus group interview were performed to capture the patients' values and preferences. Data from the National Health Insurance drug price list and product information provided by pharmaceutical companies were collected to evaluate drug cost and safety. The GRADE approach was used to describe the evidence quality and determine the strength of recommendations. Recommendations were developed using a modified Delphi method by a multidisciplinary panel including patients. Results. Eight meetings and frequent e-mail communications were conducted to draft a quality assessment of evidence and recommendations. For 88 CQs, recommendation statements were determined. Conclusions. Using the GRADE approach, new CPGs successfully addressed important clinical issues for treating RA patients. Timely updating of recommendations should be routinely considered. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the efficacy and safety of rituximab in Japanese patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) who are refractory to conventional immunosuppressive therapy. Methods. Eligible patients received rituximab at a dose of 1,000 mg at days 1, 15, 169, and 183, and were followed for 53 weeks after the first dose of rituximab. Overall disease activity was assessed monthly using a British Isles Lupus Assessment Group activity index. Patients with LN (Upr/Ucr ≥-1.0 at study entry) were identified and their renal responses were evaluated according to the criteria proposed by the American College of Rheumatology (ACR) and the Lupus Nephritis Assessment with Rituximab (LUNAR) study. Results. A total of 34 patients were enrolled and received at least one dose of rituximab. Decrease in disease activity was achieved in 16 (76.5%) out of 34 patients. In 17 patients with LN, response rates of 58.8% and 52.9% by ACR and LUNAR criteria, respectively, were seen. Successful steroid tapering was achieved in association with disease remission. Rituximab was well tolerated, and most adverse drug reactions were grade 1 - 2 in severity. Conclusions. Rituximab is effective for treatment of Japanese patients with SLE and LN refractory to conventional therapy. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate, through a systematic review of the literature, the association between the use of biological disease-modifying antirheumatic drugs (bDMARDs) and surgical site infection (SSI) or wound healing delay after orthopedic surgery in patients with rheumatoid arthritis (RA). Methods. A systematic review of articles indexed in the Cochrane Library, PubMed, and Web of Science from 1992 to 2012 was performed. The search aimed to identify studies describing SSI or wound healing delay in patients with RA treated with or without bDMARDs. Articles fulfi lling the predefi ned inclusion criteria were reviewed systematically and their quality was appraised. Results. There was no Cochrane review on this subject. We found 75 articles through specifi c searches of PubMed and Web of Science, and hand searching. After inclusion and exclusion by full-text review, 10 articles were found for SSI, and 5 articles for delayed wound healing. The use of bDMARDs appeared to increase the rate of SSI slightly, especially in large joint-replacement surgery. Delayed wound healing was not increased by the use of bDMARDs. However, the defi nitions of SSI and delayed wound healing varied between the reviewed articles. Most of the articles focused on tumor necrosis factor- a inhibitors. Conclusion. bDMARDs slightly increase the relative risk of SSI but not that of delayed wound healing after orthopedic surgery and should be used with appropriate caution. [ABSTRACT FROM AUTHOR]

It is suggested that polymyositis, an autoimmune inflammatory myopathy, is mediated by autoaggressive CD8 T cells. Skeletal muscle C protein is a self-antigen that induces C proteininduced myositis, a murine model of polymyositis. To establish a new murine model of myositis inducible with a single CD8 T-cell epitope peptide that derives from the C protein, three internet-based prediction systems were employed to identify 24 candidate peptides of the immunogenic fragment of the C protein and bind theoretically to major histocompatibility complex class I molecules of C57BL/6 (B6) mice. RMA-S cell assay revealed that a HILIYSDV peptide, amino acid position 399-406 of the C protein, had the highest affinity to the H2-Kb molecules. Transfer of mature bone marrow-derived dendritic cells pulsed with HILIYSDV induced myositis in naive B6 mice. This myositis was suppressed by anti-CD8-depleting antibodies but not by anti-CD4-depleting antibodies. Because this myositis model is mediated by CD8 T cells independently of CD4 T cells, it should be a useful tool to investigate pathology of polymyositis and develop therapies targeting CD8 T cells. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to determine whether biologic-free remission of RA is possible with discontinuation of abatacept. Methods. Japanese RA patients in 28-joint DAS with CRP (DAS28-CRP) remission (<2.3) after >2 years of abatacept treatment in a phase II study and its long-term extension entered this 52 week, multicentre, non-blinded, prospective, observational study. At enrolment, the patients were offered the option to continue abatacept or not. The primary endpoint was the proportion of patients who remained biologic-free at 52 weeks after discontinuation. Clinical, functional and structural outcomes were compared between those who continued and those who discontinued abatacept. Results. Of 51 patients enrolled, 34 discontinued and 17 continued abatacept treatment. After 52 weeks, 22 of the 34 patients (64.7%) remained biologic-free. Compared with the continuation group, the discontinuation group had a similar remission rate (41.2% vs 64.7%, P = 0.144) although they had a significantly higher mean DAS28-CRP score at week 52 (2.9 vs 2.0, P = 0.012). The two groups were also similar with regard to mean HAQ Disability Index (HAQ-DI) score (0.6 for both, P = 0.920), mean change in total Sharp score (ΔTSS; 0.80 vs 0.32, P = 0.374) and proportion of patients in radiographic remission (ΔTSS ≤ 0.5) at the endpoint (64.3% vs 70.6%, P = 0.752). Those attaining DAS28-CRP<2.3 or<2.7 without abatacept at the endpoint had significantly lower HAQ-DI score and/ or CRP at enrolment. Non-serious adverse events occurred in three patients who continued or resumed abatacept. Conclusion. Biologic-free remission of RA is possible in some patients after attaining clinical remission with abatacept. Lower baseline HAQ-DI or CRP may predict maintenance of remission or low disease activity after discontinuation of abatacept. Trial registration: UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/ (UMIN000004137). [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to compare efficacy outcomes of initial treatment with adalimumab +MTX vs adalimumab addition following 26 weeks of MTX monotherapy in Japanese early RA patients naive to MTX with high disease activity. Methods. Patients completing the 26-week, randomized, placebo-controlled trial of adalimumab +MTX were eligible to receive 26 weeks of open-label adalimumab + MTX. Patients were assessed for mean change from baseline in the 28-joint DAS with ESR (DAS28-ESR) and modified total Sharp score (mTSS), and for the proportions of patients achieving clinical, functional or radiographic remission. Results. Of 333 patients assessed, 278 (137 from the initial adalimumab +MTX and 141 from the initial placebo +MTX groups) completed the 52-week study. Significant differences in clinical and functional parameters observed during the 26-week blinded period were not apparent following the addition of open-label adalimumab to MTX. Open-label adalimumab +MTX slowed radiographic progression through week 52 in both groups, but patients who received adalimumab +MTX throughout the study exhibited less radiographic progression than those who received placebo +MTX during the first 26 weeks (mean ΔmTSS at week 52 = 2.56 vs 3.30, P<0.001). Conclusion. Delayed addition of adalimumab in Japanese MTX-naive early RA patients did not impact clinical and functional outcomes at week 52 compared with the earlier addition of adalimumab. However, the accrual of significant structural damage during blinded placebo +MTX therapy contributed to the persistence of differences between the treatment strategies, suggesting that Japanese patients at risk for aggressive disease should benefit from the early inclusion of adalimumab +MTX combination therapy. [ABSTRACT FROM AUTHOR]

The third complementarity-determining region (CDR3) of TCR interacts directly with antigenic peptides bound to grooves of MHC molecules. Thus, it is the most critical TCR structure in launching acquired immunity and in determining fates of developing thymocytes. Since length is one of the components defining the CDR3 heterogeneity, the CDR3 length repertoires have been studied in various T cell subsets from humans in physiological and pathological conditions. However, how the CDR3 length repertoire develops has been addressed only by a few reports, including one showing that CDR3 of CD4 thymocytes becomes shorter during thymic development. Here, we explored multiple regulations on the development of the TCRB CDR3 length repertoires in the thymus and the peripheral blood. CDR3 length spectratyping was employed to examine thymocyte and peripheral T cell populations for their CDR3 length repertoires. We have found that repertoire distribution patterns depend on use of the BV gene. The BV-dependent patterns were shaped during thymic selections and maintained in the peripheral blood. Differences in the mean CDR3 length among different BV subsets were seen throughout lymphocyte development. We also observed that CDR3 was shortened in both CD4 and CD8 thymocytes. Of note, the degrees of the shortening depended on the CD4/CD8 lineage and on use of the BV gene. When expansions of peripheral T cell clones are negligible, no obvious difference was seen between mature thymocytes and peripheral lymphocytes. Thus, the TCRB CDR3 length repertoires are finely tuned in the thymus before the lymphocytes emigrate into the peripheral blood. [ABSTRACT FROM AUTHOR]