Effectiveness of tacrolimus concomitant with biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

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.

Improvement in matrix metalloproteinase-3 independently predicts low disease activity at 52 weeks in bio-switch rheumatoid arthritis patients treated with abatacept.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

High rate of improvement in serum matrix metalloproteinase-3 levels at 4 weeks predicts remission at 52 weeks in RA patients treated with adalimumab.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors for rheumatoid arthritis in Japanese patients on low-dose methotrexate or without methotrexate.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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%, p < 0.001, 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. CONCLUSIONS: 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.

Change in ground reaction force parameters according to the frailty level of older women in the Timed Up and Go test.

As older people become frail, they tend to fall more easily. Moreover, women have a higher rate of falls than men. However, effective strategies to avoid elderly women falling are lacking. The Timed Up and Go test is a well-known indicator of falling tendency. This study clarifies the motor elements related to the Timed Up and Go test according to the degree of weakness in older outpatients to specify exercise intervention to improve weakness and prevent falls. Participants were 145 female outpatients who visited the Locomo-Frail outpatient clinic, classified into three groups (robust, prefrail, and frail, according to the definition of the Japanese Cardiovascular Health Study. Vertical ground reaction force parameters were measured for all participants when they stood up from a chair, walking speed, and the Timed Up and Go test. Results showed that walking speed is related to the Timed Up and Go test in the robust group; balance ability is related to the Timed Up and Go test in the prefrail group; and instantaneous force is related to the Timed Up and Go test in the frail group. These results suggest that weakness can be improved by performing exercise interventions of balance and instantaneous force elements in the prefrail and frail groups, respectively.

Influences of anti-tumour necrosis factor agents on postoperative recovery in patients with rheumatoid arthritis.

The aim of this study is to investigate the influences of the anti-tumour necrosis factor (TNF) agents infliximab and etanercept on the postoperative recovery of patients with rheumatoid arthritis (RA). We also investigated the effects of biologics on wound healing. Patients with RA were split into a TNF group (n = 39) that underwent 39 operations and were treated with anti-TNF agents, and a non-TNF group (n = 74) that underwent 74 operations and were treated only with conventional disease-modifying antirheumatic drugs. Operations included ankle arthrodesis and total arthroplasty of the hip, knee, elbow, shoulder and ankle. Adverse events (AEs) of surgical wounds, time for complete wound healing, febrile period after operation and recovery parameters after operation (%recovery of haemoglobin (Hb), total protein and albumin at 4 weeks after operation compared with pre-operation levels) were investigated. AEs of surgical wounds occurred in two operations (5.1%) in the TNF group and in five operations (6.8%) in the non-TNF group, but this difference was not statistically significant. There were also no significant differences in the time for complete wound healing and in the length of the febrile period between the two groups. Percentage recovery of Hb was significantly better in the TNF group than in the non-TNF group (96.3% vs. 90.1%, respectively; p < 0.05). These results suggest that the use of anti-TNF agents does not cause specific AEs on surgical wounds after elective orthopaedic operations in RA patients and might improve the percentage recovery of Hb due to its prompt anti-TNF effects.