Association between P1NP value and increases in bone mineral density in patients with postmenopausal osteoporosis treated with romosozumab.

OBJECTIVES: The present study aimed to investigate the effectiveness of treatment with romosozumab for one year and association between bone turnover markers and changes in bone mineral density (BMD) in patients with postmenopausal osteoporosis (PMO). METHODS: Participants were 53 treatment-naïve PMO patients. Correlations of percent changes (Δ) in lumbar (L) and total hip (TH) BMD 12 months after initiating romosozumab with baseline demographic factors and parameters of N-terminal propeptide of type 1 collagen (P1NP) and tartrate-resistant acid phosphatase (TRACP)-5b at baseline and months 1, 3 and 6 were assessed. Multiple regression analysis was performed on factors significantly correlated with ΔL-BMD and ΔTH-BMD at month 12. RESULTS: ΔL-BMD and ΔTH-BMD at month 12 were 17.5% and 8.1%, respectively. Multiple regression analysis revealed that a high P1NP value at month 3 predicted large increases in L-BMD and TH-BMD at month 12. High total amount of P1NP values from baseline to month 6 was associated with large increases in L-BMD and TH-BMD at month 12, and was most strongly correlated with the P1NP value at month 3. CONCLUSIONS: A high P1NP value at month 3 predicted large increases in both L-BMD and TH-BMD at month 12 in PMO patients treated with romosozumab.

Comparable efficacy of denosumab and romosozumab in patients with rheumatoid arthritis receiving glucocorticoid administration.

OBJECTIVES: Romosozumab is a newly released and widely known molecular-targeted drug for severe osteoporosis treatment with comparable effectiveness to denosumab. However, there have been no reports discussing the efficacy of those treatments for rheumatoid arthritis (RA) patients, especially those receiving glucocorticoids. This retrospective observational registry study compared the efficacy of 12-month treatment of denosumab and romosozumab in RA patients under the influence of glucocorticoid intake. METHODS: Following propensity score matching, 36 patients each in the denosumab and romosozumab groups were analysed in this study. Drug effectiveness was evaluated by measuring bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck at baseline, 6 and 12 months as well as alterations in P1NP, TRACP-5b, and simplified disease activity index (SDAI). The occurrence of adverse events and new fractures was also assessed. RESULTS: At 12 months of treatment, BMD at the lumbar spine was increased by 7.5% in the denosumab group and 8.7% in the romosozumab group, which were both significantly and comparably elevated over baseline. At the total hip and femoral neck, romosozumab tended to exhibit favourable efficacy to increase BMD versus denosumab. Both P1NP and TRACP-5b were significantly lower in the denosumab group as compared with the baseline. Conversely in the romosozumab group, P1NP was increased over baseline, while TRACP-5b was decreased. Regarding SDAI alterations, both the romosozumab and denosumab groups exhibited comparable improvements in RA disease activity over time during treatment. Recorded adverse events and new fractures during treatment were few and minor in both groups. CONCLUSIONS: Romosozumab exhibited comparable efficacy to denosumab for increasing BMD even under the influence of glucocorticoids for treating RA. Both drugs may be therefore suitable for managing osteoporosis in patients with RA and glucocorticoid intake.

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.

Reasons and risk factors for discontinuation of treatment with any biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: A long-term observational study.

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 (<65 years old, n = 413; ≥65, n = 151). The primary outcome was the incidence of bDMARDs discontinuation due to adverse events (AEs). Risk factors were examined using Fine and Gray regression models. 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 <65 years, respectively. The subdistribution hazard ratio for discontinuation was significantly higher in the ≥65 group than in the <65 years group (hazard ratio = 3.53, 95% confidence interval = 2.07-6.03). Lack of concomitant treatment with MTX was risk factor for discontinuation in patients ≥65 years. Advanced Steinbrocker class was a risk factor in patients <65 years. CONCLUSIONS: Older patients are at higher risk of discontinuing bDMARDs treatment due to AEs than younger patients.

Do heel-unloading orthoses improve clinical outcomes in patients after surgical treatment of calcaneal fracture? A propensity-matched, multicenter analysis of the TRON database.

BACKGROUND: 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. OBJECTIVES: The purpose of this study was to compare postoperative radiologic and clinical outcomes in patients with calcaneal fractures who used Graffin orthosis. STUDY DESIGN: Multicenter retrospective study. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Plate fixation through the lateral extensile approach versus cannulated screw fixation through the sinus tarsi approach for calcaneal fracture: a multicenter, propensity score-matched TRON study.

PURPOSE: For calcaneal fracture, plate fixation through lateral extensive approach (LEP) is the most common procedure performed to achieve anatomic reduction. However, wound complications sometimes occur after LEP. To reduce complications, minimally invasive operative methods with cannulated screw fixation through sinus tarsi approach (STS) were developed. The aim of this multicenter propensity-matched study was to compare the clinical and radiographic outcomes of LEP to those of STS for calcaneal fracture and to evaluate the incidence of postoperative complications including surgical site infection (SSI). METHODS: We extracted 271 patients with calcaneal fracture undergoing surgery between January 2014 and March 2019 from our multicenter TRON database. We assessed the American Orthopedic Foot and Ankle Society (AOFAS) score at the final follow-up as the clinical outcome. We obtained the Bohler and Preis angles as radiographic parameters and also recorded the complications. We divided the subjects into two groups: LEP group and STS group. To adjust for baseline differences between the groups, a propensity score matching algorithm was used in a 1:1 ratio. RESULTS: After matching, there were 32 fractures in each group. There was no significant difference between the LEP versus STS group in AOFAS score at final follow-up (90 vs 90 points, p = 0.98) and in the Bohler and Pries angles (19.2 vs. 18.0 degrees, p = 0.74 and 16.0 vs. 17.5 degrees, p = 0.47). The rate of SSI in the LEP group was higher than that in the STS group (21.9% vs. 0.0%, p = 0.01). CONCLUSION: For calcaneal fracture, STS provides similar fixation effectiveness and functional outcomes as LEP while reducing the likelihood of infection.

The Association of Bohler's Angle With Postoperative Pain and Gender for Displaced Intra-Articular Calcaneal Fracture, Multicenter Retrospective Study-TRON Study.

A relationship between Böhler angle (BA) before or after surgery and clinical outcomes remains unclear. This retrospective multicenter cohort study aimed to compare pain and functional outcomes between a group in which the reduction angle was preserved and a group in which the reduction angle was lost during follow-up, and to clarify the risk factors leading to loss of last follow-up BA. From 2014 to 2018, 271 cases of calcaneal fractures were surgically treated at ten facilities. We divided patients into Group L (lost reduction of fracture) and Group P (preserved reduction of fracture). We matched subjects between the 2 groups according to age, sex and BA before surgery and compared American Orthopedic Foot and Ankle Society (AOFAS) score between the groups. We investigated the correlation between the amount of BA loss and postoperative pain. The factors leading to loss of last follow-up BA were examined by logistic regression analysis. Ultimately, 112 patients were eligible. After matching, each group included 38 patients. There was no difference between the 2 groups in total AOFAS score. However, the pain component of AOFAS score at 6 months and 12 months were worse in group L than in group P (p = .011, p = .031, respectively). We also showed a weak correlation between the amount of BA loss and postoperative pain. Logistic regression analysis revealed that female and BA before surgery independently predicted loss of reduction (odds ratios: 4.66, 95% CI: 1.15-18.9 and odds ratios: 0.90, 95% CI: 0.82-0.99, respectively). We clarified that reduction and preservation of BA within its normal range should lead to decrease postoperative pain. Female and lower pre-BA were risk factors leading to loss of reduction of BA in operative treatment of calcaneal fractures.

Comparison of the effects of baricitinib and tocilizumab on disease activity in patients with rheumatoid arthritis: a propensity score matching analysis.

OBJECTIVE: This study aimed to compare the effects of baricitinib, a Janus kinase inhibitor, and tocilizumab, a monoclonal anti-interleukin-6 receptor antibody, on disease activity in patients with rheumatoid arthritis (RA), and to investigate the influence of inflammation on improvement in patient global assessment (PGA) of disease activity. METHODS: This study was performed based on data from a multicenter registry, and included 284 and 113 patients treated with tocilizumab and baricitinib, respectively, who were observed for longer than 24 weeks. Propensity score matching was performed to address potential treatment-selection bias. To assess the influence of inflammation on PGA, patients were divided into two groups based on whether or not they achieved improvement in C-reactive protein (CRP, an objective marker of inflammation) at 24 weeks. RESULTS: A total of 48 matched pairs of patients were identified. Compared to treatment with tocilizumab, baricitinib showed a similar improvement in tender and swollen joint count and serum CRP levels, and a significantly greater improvement in PGA at 24 weeks. As a result, the baricitinib group had a significantly higher proportion of patients who achieved Boolean remission at 24 weeks. In subgroups of patients who did not achieve 50% or 70% CRP improvement, significant decreases from baseline to 24 weeks were observed in PGA in patients treated with baricitinib, but not in those treated with tocilizumab. CONCLUSION: Compared to tocilizumab, baricitinib significantly improved PGA despite similar effects on inflammation in patients with RA. Moreover, the influence of inflammation on PGA improvement differed between baricitinib and tocilizumab. Key-points • Baricitinib and tocilizumab had similar effects on inflammation in RA patients. • Baricitinib improved patient global assessment (PGA) more than tocilizumab. • Baricitinib had a higher Boolean remission rate than tocilizumab at 24 weeks. • Influence of inflammation on PGA improvement differed between the two drugs.

Higher doses of methotrexate associated with discontinuation of oral glucocorticoids after initiation of biological DMARDs: A retrospective observational study based on data from a Japanese multicenter registry study.

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

Efficacy of add-on iguratimod in patients with rheumatoid arthritis who inadequately respond to either tocilizumab or tumor necrosis factor alpha inhibitors.

OBJECTIVES: This study aimed to evaluate the efficacy of add-on iguratimod (IGU) in patients with rheumatoid arthritis (RA patients) who inadequately respond to either tocilizumab (TCZ) or tumor necrosis factor alpha inhibitors (TNFi). METHODS: Twenty-three RA patients treated with TCZ (the TCZ group) and 23 RA patients treated with TNFi (the TNFi group) were enrolled in this 24-week retrospective study from our multicenter registry. All inadequate responders to either TCZ or TNFi received add-on IGU. Baseline demographics and disease activity at 24 weeks after initiating add-on IGU were compared between the two groups. RESULTS: Baseline clinical disease activity index (CDAI) values in the TCZ group and TNFi group were 14.1 and 11.8 (p = .24 between the two groups). At 24 weeks, CDAI values in the TCZ group and TNFi group were 5.1 and 7.5 (p = .002 and .002 compared to baseline, respectively) and ΔCDAI values were -9.0 and -4.3 (p = .007 between the two groups). Multiple linear regression analysis revealed that add-on IGU in the TCZ group was associated with greater improvement in CDAI relative to the TNFi group. CONCLUSION: Add-on IGU was more effective in inadequate responders to TCZ than in inadequate responders to TNFi.

Predictors for clinical effectiveness of baricitinib in rheumatoid arthritis patients in routine clinical practice: data from a Japanese multicenter registry.

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.

A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and the effectiveness of abatacept in rheumatoid arthritis patients.

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.

Predictors of disease flare after discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis treated with tocilizumab.

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≥12weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12weeks 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 (52weeks 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 4weeks, or subcutaneously every 2weeks) 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.

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.

Discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis treated with tocilizumab: An interventional study.

Objectives: To evaluate the efficacy and safety of methotrexate (MTX) discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing combination therapy with tocilizumab (TCZ) plus MTX.Methods: This multicenter, open-label, uncontrolled, prospective study included RA patients maintaining low disease activity (Clinical Disease Activity Index (CDAI) ≤10) for ≥12 weeks with TCZ plus MTX. Methotrexate was discontinued following 12 weeks of biweekly administration while continuing TCZ therapy. The primary endpoint was the proportion of patients maintaining low disease activity with no flare at week 36.Results: A total of 49 patients completed 36 weeks of therapy. The proportion of patients maintaining low disease activity at week 36 was 75.5%. The lower limit of the 95% confidence interval exceeded the assumed threshold response rate of 60%, demonstrating the clinical feasibility of MTX discontinuation. The prevalence of gastroesophageal reflux disease, defined as a Frequency Scale for Symptoms of Gastroesophageal reflux disease score ≥8, significantly decreased from week 0 to 12 (27.1-18.4%; p= .025).Conclusion: Discontinuation of concomitant MTX is clinically feasible for maintaining low disease activity, and may be beneficial from the perspective of reducing gastrointestinal symptoms in Japanese RA patients treated with TCZ. Trial registration number: UMIN000021247.

Predictors of denosumab efficacy in treating osteoporosis in patients with rheumatoid arthritis: a Japanese multicenter study.

We investigated 2-year outcomes of denosumab treatment for osteoporosis in patients with rheumatoid arthritis (RA) and predictors of good outcomes. Study participants were 74 females treated with denosumab for 24 months. After investigating baseline demographics and overall time course for each patient, we divided all cases into two groups according to percent change (%) in bone mineral density (BMD) of lumbar spine (LS-) and total hip (TH-) at 24 months (-24m); two thirds of the patients were allocated to the good outcome group (LS-GO and TH-GO), and the other third to the non-good outcome group (LS-NG and TH-NG). We performed multivariate analysis to confirm predictors of greater increases in LS- and TH-BMD. LS-BMD-24m and TH-BMD-24m increased significantly from baseline. We observed greater %LS-BMD-24m in LS-GO group than in LS-NG group, while %TH-BMD-24m showed no significant group-dependent difference. N-terminal propeptide of type 1 collagen (P1NP) and tartrate-resistant acid phosphatase (TRACP)-5b decreased more in LS-GO group than in LS-NG group at each time point. We observed greater %TH-BMD-24m in TH-GO group than in TH-NG group, while %LS-BMD-24m showed no significant group-dependent difference. Only P1NP-6m showed a larger decrease in TH-GO group relative to TH-NG group. Multivariate analysis confirmed that the larger decrease in P1NP-6m was associated with the greater increase in LS-BMD-24m, while the combined use of biologics was associated with the greater increase in TH-BMD-24m. In conclusions, denosumab increased BMD in RA patients with osteoporosis. The combined use of biologics and denosumab may provide useful treatment options.

Association between seropositivity and discontinuation of tumor necrosis factor inhibitors due to ineffectiveness in rheumatoid arthritis.

INTRODUCTION/OBJECTIVES: 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. METHOD: 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. RESULTS: 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)]. CONCLUSIONS: 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.

Concomitant methotrexate has little effect on clinical outcomes of abatacept in rheumatoid arthritis: a propensity score matching analysis.

OBJECTIVE: To compare the clinical outcomes of abatacept between rheumatoid arthritis patients with and without concomitant methotrexate (MTX) treatment in daily clinical practice. METHODS: 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. RESULTS: 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. CONCLUSION: 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. KEY POINTS: • 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.

Clinical effectiveness and long-term retention of abatacept in elderly rheumatoid arthritis patients: Results from a multicenter registry system.

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.

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.