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Aim: Patient Global Assessment (PtGA; range 0–10 cm) is an important indicator of clinical outcomes, including physical function, in self-assessment of patients with rheumatoid arthritis (RA). Frailty is a concept that encompasses not only physical, but also mental, psychological and social vulnerability. This study aimed to investigate the influence of frailty on PtGA in patients with RA. Methods: Among 581 patients with RA who completed a questionnaire survey on frailty between June and August 2020, 559 who completed the Kihon Checklist (KCL; a 25-item questionnaire with seven domains) were included. The proportion of patients with PtGA ≤1 was compared between the frailty (KCL score ≥8), pre-frailty (KCL score 4–7) and robust (KCL score 0–3) groups. Factors associated with PtGA ≤1 were examined using multivariate logistic regression models. Results: Of the 559 patients, 221 (39.5%) had frailty. The proportion of patients with PtGA ≤1 was significantly lower in the frailty group (33.9%) than in the robust (65.4%, P

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 This study aimed to evaluate the association between locomotive syndrome (LS) and frailty in rheumatoid arthritis (RA) patients. Methods Subjects were 538 RA patients (female, 72.9%; mean age ± standard deviation, 66.8 ± 13.4 years). LS and frailty were defined as ≥16 points on the 25-question Geriatric Locomotive Function Scale (Stage ≥2) and ≥8 points on the Kihon Checklist (KCL), respectively. Results There were 214 subjects with Stage ≥2 LS (39.8%) and 213 subjects with frailty (39.6%). Among subjects with Stage 0, 1, 2, and 3 LS, 11.0%, 21.9%, 48.3%, and 84.6% had frailty, respectively. The KCL points for cognitive and psychosocial factors had no significant differences across LS stages. Multivariable logistic regression analysis revealed that the Health Assessment Questionnaire was independently associated with frailty and LS stage, and the Clinical Disease Activity Index was associated with LS stage but not frailty. Conclusions As LS worsens in RA patients, the likelihood of developing physical frailty increases. RA patients with a low LS stage can still develop frailty, and suppressing disease activity may not be sufficient to prevent frailty. These findings highlight the need to screen for frailty in RA patients and consider appropriate interventions based on each patient’s condition, focusing on nonphysical factors.

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.

Rheumatoid arthritis (RA) patients often exhibit finger/wrist joint symptoms and reduced grip strength. This study aimed to validate grip strength as a measure of frailty in RA patients. Subjects were 424 female RA patients (mean age±standard deviation, 66.8±14.5 years). Frailty was defined as a score of ≥8 points on the Kihon Checklist (KCL). Finger/wrist joint symptoms were defined based on tender or swollen joints. Associations between frailty and grip strength were determined using receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis. There were 179 subjects with frailty (42.2%). Multivariable logistic regression analysis revealed that frailty was significantly associated with grip strength independently of finger/wrist joint symptoms. In ROC curves, cut-off scores of grip strength for frailty in subjects without and with finger/wrist joint symptoms were 17 kg (sensitivity, 62.1%; specificity, 69.0%) and 14 kg (sensitivity, 63.2%; specificity, 73.0%), respectively. The results of the present study suggest that grip strength in female RA patients is associated with frailty, with a cut-off score of 17 kg (equivalent to Cardiovascular Health Study criteria

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.

This study aimed to longitudinally evaluate the development of locomotive syndrome (LS) in rheumatoid arthritis (RA) patients during the COVID-19 pandemic using the 25-question Geriatric Locomotive Function Scale (GLFS-25). Subjects were 286 RA patients (female, 70.6%; mean age, 64.2 years) who had GLFS-25 and Clinical Disease Activity Index (CDAI) data available for a 1-year period during the COVID-19 pandemic and who did not have LS at baseline. Associations between subject characteristics and development of LS were determined using logistic regression analysis. Among the 286 patients, 38 (13.3%, LS group) developed LS at 1 year after baseline. In the LS group, scores of the GLFS-25 categories "GLFS-5" and "Social activities" were significantly increased at 1 year relative to baseline. GLFS-5 is a quick 5-item version of the GLFS-25, including questions regarding the difficulty of going up and down stairs, walking briskly, distance able to walk without rest, difficulty carrying objects weighing 2 kg, and ability to carry out load-bearing tasks and housework. A significant correlation was also observed between changes in "Social activities" and that of "GLFS-5." Multivariable logistic regression analysis revealed that the development of LS was significantly associated with BMI (OR: 1.11 [95% confidence interval (CI): 1.00-1.22]) and CDAI (OR: 1.08 [95%CI: 1.00-1.16]) at baseline. Adequate exercise and tight control of RA disease activity are important for preventing the development of LS in view of restrictions on going out imposed during the COVID-19 pandemic. GLFS-5 is useful for evaluating the physical function of RA patients.

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.

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.

This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA).Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP) 2.3) at 52 weeks were evaluated by multivariate logistic regression analysis.DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382-0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002-1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively.Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.

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

Objective.To evaluate the rates of retention and discontinuation of adalimumab (ADA) due to efficacy and safety in Japanese patients with rheumatoid arthritis (RA).Methods.All patients with RA (n = 476) who were treated with ADA in the Tsurumai Biologics Communication Registry were enrolled.Results.The retention rate of ADA was 46% at 5 years. When focusing on insufficient efficacy, previous biologics use and high baseline disease activity were significant risk factors for up to 1 year. Methotrexate (MTX) use was a significantly low risk factor after 1 year of treatment.Conclusion.Concomitant MTX contributes to the longterm efficacy of ADA therapy.

The objective of this study is to evaluate the efficacy of golimumab (GLM) in Japanese patients with active rheumatoid arthritis (RA) for 1 year. Nineteen patients were enrolled; 9 were randomized to the placebo (PBO) + methotrexate (MTX), GLM 50 mg + MTX, or GLM 100 mg + MTX therapy group; and 10 were randomized to the PBO, GLM 50 mg, or GLM 100 mg therapy group. One patient in the GLM 100 mg + MTX therapy group with median values from the GO-FORTH study was added. Data were evaluated by assessing the changes in DAS28-ESR, Health Assessment Questionnaire Disability Index (HAQ-DI), and total Sharp score (TSS) at week 52. Mean changes in DAS28-ESR in the MTX monotherapy, GLM 50 mg + MTX, GLM 100 mg + MTX, PBO, GLM 50 mg, and GLM 100 mg therapy groups were -2.70, -2.57, -2.27, -0.60, -2.53, and -2.53, respectively; the mean improvements in HAQ-DI were 0.188, 0.708, 0.377, 0.188, 1.042, and 0.625, respectively. The mean changes in TSS were 1.63, -0.33, -1.17, 4.25, 1.00, and 1.67, respectively. A significant difference was only observed in the mean TSS change between the PBO + MTX and the GLM 100 mg + MTX groups. However, in terms of mean changes in DAS28-ESR in the combination therapy groups, PBO + MTX therapy seemed to elicit similar results as the GLM 50 mg + MTX and GLM 100 mg + MTX therapies (no significant difference) because all four patients in the PBO + MTX therapy group may have received GLM from week 24 as a crossover. Combined GLM + MTX therapy reduced disease activity and strongly inhibited radiographic disease progression in patients with active RA at week 52.

Quinoxaline derivatives having bis(fluoromethyl), bis(chloromethyl), or bis(iodomethyl) groups at the 2- and 3-positions, and various electron-donating/withdrawing substituents at the 6- and/or 7-positions, were synthesized. Their antibacterial and antifungal activities were evaluated by means of minimum inhibitory concentration assays. The relationships between the substituents and the antimicrobial activities of the quinoxaline derivatives indicate that the electrophilicity of the halomethyl units plays an important role in generating the antimicrobial activity.

The inflammatory cytokine interleukin-6 (IL-6) directly stimulates C-reactive protein (CRP) expression. The present study aimed to examine how clinical treatment outcomes of rheumatoid arthritis (RA) with tocilizumab (TCZ), a humanised monoclonal anti-IL-6 receptor antibody, are related to CRP levels monitored for 52 weeks.One hundred and twenty-two RA patients who underwent TCZ treatment between May 2008 and September 2009 were registered in the Tsurumai Biologics Communication Registry. Data were collected at initiation of treatment (baseline) and over 52 weeks for Disease Activity Score 28-ESR (DAS28-ESR), Boolean core measurements, serum CRP levels and matrix metalloproteinase-3 levels. To compare clinical results, patients were divided into three groups based on treatment time required to achieve normal CRP levels.Multivariate analysis using the Cox proportional-hazards regression model found that higher CRP levels at baseline was a significant and independent factor in predicting normal CRP levels over 52 weeks (hazard ratio 0.86 per 1 mg/dL). In contrast, disease duration, concomitant methotrexate use and previous tumour necrosis factor inhibitor failure were not significant factors. Patients with normal CRP levels at 12 weeks of TCZ treatment achieved better clinical outcomes, including remission based on DAS28-ESR criteria, compared to patients with elevated CRP levels at 12 weeks.Adequate suppression of pathological IL-6 signalling during TCZ treatment improves clinical outcomes and can be monitored with serum CRP levels, a readily available biomarker in clinical practice.

The goal of treating rheumatoid arthritis (RA) should be remission, for which a new definition was proposed in 2011. To determine which patients can achieve the new Boolean-based definition of remission in clinical practice, we analyzed factors associated with remission in 123 patients who received tocilizumab for 52 weeks. We found that patients with short disease duration (

We report a case of a 65-year-old man with rheumatoid arthritis. The patient was treated with methotrexate and prednisolone, but the disease activity remained high. A tuberculin skin test was positive. After antituberculosis (TB) chemoprophylaxis with isoniazid for four weeks, infliximab was administered. Chemoprophylaxis was continued for nine months. Active lung TB was diagnosed at 17 months after the cessation of isoniazid, namely at 27 months after starting infliximab treatment. This case report shows that TB can manifest after chemoprophylaxis in patients treated with antitumor necrosis factor agents.

This study aimed to compare the long-term safety of biologics by initiation year of treatment in patients with rheumatoid arthritis (RA) in Japan. RA patients who started their first biologics including infliximab, etanercept, adalimumab, and tocilizumab between 2003 and 2008 were identified in the Tsurumai Biologics Communication Registry (TBCR), multicenter observational cohort, and followed for 2 years or until discontinuation of the drugs. We identified baseline predictors for adverse events (AEs) resulting in discontinuation of the first TNFI using Cox proportional hazards regression analysis. A total of 874 cases (1,340 person-years) were observed. During the observation period, 96 AEs (4.7 events/100 person-years) occurred. From 2003 to 2008, there were significant changes in disease duration, Steinbrocker stage, and disease activity in those aged ≤64 years with no increase of incidence of AEs, whereas those aged >64 years had no significant changes in these variables. In the later initiation year of treatment with biologics, the fewer AEs were observed (log-rank, p = 0.017, 2008 vs. 2003-2005). Multivariate analysis showed that the initiation year significantly impacted the incidence of AEs 6 months into the observation period [initiation at 2008 (vs. 2003-2005): OR: 0.30, 95 % CI: (0.14-0.68)] after adjusting for variables at baseline. The decrease of AEs in the later initiation year was evident in those aged >64 years. The safety of biologic therapy improved over the course of the 8 years from its implementation in Japan.

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.

Quinoxaline derivatives having bis(fluoromethyl), bis(chloromethyl), or bis(iodomethyl) groups at the 2- and 3-positions, and various electron-donating/withdrawing substituents at the 6- and/or 7-positions, were synthesized. Their antibacterial and antifungal activities were evaluated by means of minimum inhibitory concentration assays. The relationships between the substituents and the antimicrobial activities of the quinoxaline derivatives indicate that the electrophilicity of the halomethyl units plays an important role in generating the antimicrobial activity.

We synthesized 12 derivatives of 2,3-bis(bromomethyl)quinoxaline with substituents at the 6- and/or 7-positions, and evaluated their activities against bacteria and fungi. Of the 12 compounds, nine (1a-h, 1j, and 1k) showed antibacterial activity. The derivative 1g, which bears a trifluoromethyl group at the 6-position, showed the highest activity against Gram-positive bacteria, while 1c, which has a fluoro-group at the 6-position, showed the widest antifungal activity spectrum. However, only the derivative with an ethyl ester substitution, 1k showed activity against Gram-negative bacteria.

Biologic agents have proven to be effective against rheumatoid arthritis (RA) in clinical trials and post-marketing surveillance (PMS) studies. However, limited follow-up periods and strict criteria for recruitment might lead to an underestimation of adverse events. To document the long-term course of patients with RA treated with biologics in clinical settings, we established the Tsurumai Biologics Communication Registry (TBCR). First, we retrospectively collected data of patients registered for any biologic PMS study or clinical trial at participating institutes. Thus far, thirteen institutes have joined the registry and 860 patients have been identified. Comparing baseline characteristics by age and initiation year of biologics, young patients had significantly less joint damage and dysfunction and a higher dose of concomitant methotrexate (MTX) compared to older patients. Older age and functional class were significantly related to the incidence of adverse events that resulted in discontinuation of the 1st biologic treatment. The TBCR is in its initial stages, and information on all patients newly starting biologic therapy at participating institutes is being collected prospectively. Differences in baseline characteristics by age and initiation year of biologics need to be carefully evaluated in order to report on drug-related survival and long-term prognosis, using follow-up data in the near future.

Since the osteogenic potential of bone marrow derived mesenchymal stem cells (BMSCs) becomes reduced with passage, establishment of culture condition that permit the rapid expansion of BMSCs while retaining their potential for differentiation is needed for clinical application. Bone morphogenetic proteins stimulate osteogenic differentiation in mesenchymal progenitor cells as well as increase stem cell numbers. Thus, we analyzed the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the osteogenic potential of rat BMSCs over several passages.Osteogenic differentiation in vitro was evaluated in terms of the alkaline phosphatase (ALP) activity and the osteocalcin (OC) concentration in the supernatants, and the expression of ALP and OC mRNA in the cultured cells. For in-vivo osteogenesis, BMSCs cultured with and without rhBMP-2 through all passages were implanted into athymic mice.The levels of osteogenic markers were significantly higher in the cells of the BMP(+) group than in the cells of the BMP(-) group, although they decreased with passage irrespective of whether or not rhBMP-2 was added. Similar to the in-vitro experiments, there was a greater degree of bone and cartilage tissue formation in the BMP(+) group over all passages.From our results, osteogenic potential can be maintained even in BMSCs that have been passaged several times in the presence of rhBMP-2. These cells are capable of inducing and participating in bone formation and can be used for clinical applications.

Favourable clinical results in rheumatoid arthritis (RA) patients with high disease activity (HDA) are difficult to achieve. This study evaluated the clinical efficacy of abatacept according to baseline disease activity compared to adalimumab and tocilizumab. This study included all patients registered in a Japanese multicenter registry treated with abatacept (n = 214), adalimumab (n = 175), or tocilizumab (n = 143) for 24 weeks. Clinical efficacy of abatacept in patients with HDA (DAS28-CRP > 4.1) and low and moderate disease activity was compared. Clinical efficacy of abatacept, adalimumab, and tocilizumab was compared in patients with HDA at baseline. In patients treated with abatacept, multivariate logistic regression identified HDA at baseline as an independent predictor for achieving low disease activity (LDA; DAS28-CRP