scholarly journals The Efficacy of Denosumab in Patients With Rheumatoid Arthritis: A Systematic Review and Pooled Analysis of Randomized or Matched Data

2022 ◽  
Vol 12 ◽  
Author(s):  
Qiongwen Hu ◽  
Xue Zhong ◽  
Hua Tian ◽  
Pu Liao
Keyword(s):  
Rheumatoid Arthritis ◽  
Random Effect ◽  
Joint Destruction ◽  
Joint Space ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Mineral Density ◽  
Erosion Score ◽  
Hip Bmd ◽  
Denosumab Treatment

ObjectiveThe purpose of this study was to evaluate the efficacy of denosumab treatment in patients with rheumatoid arthritis (RA).MethodsThe Medline, Embase and Cochrane Library databases were searched for relevant clinical studies. Studies that assessed the efficacy of denosumab in patients with RA were identified. The primary endpoints were the percent changes in bone mineral density (BMD), and the changes in modified total Sharp score (mTSS), modified Sharp erosion score and joint space narrowing (JSN) score. Pooled analyses were calculated using random-effect models.ResultsAfter searching the literature and performing further detailed assessments, 10 studies with a total of 1758 patients were included in the quantitative analysis. Pooled analyses showed that denosumab treatment significantly increased the percent changes in lumbar spine BMD [mean difference (MD): 5.12, confidence intervals (CI): 4.15 to 6.09], total hip BMD (MD: 2.72, 95% CI: 1.80 to 3.64) and femoral neck BMD (MD: 2.20, 95% CI: 0.94 to 3.46) compared with controls. Moreover, denosumab treatment significantly decreased the changes in mTSS (MD: -0.63, 95% CI: -0.86 to -0.41) and modified Sharp erosion score (MD: -0.62, 95% CI: -0.88 to -0.35). Subgroup analysis indicated that denosumab was superior to bisphosphonates for the improvement of BMD and the mitigation of joint destruction.ConclusionDenosumab treatment was associated with increased BMD and alleviated progression of joint destruction in RA patients, even when compared with bisphosphonates.

scholarly journals Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose–response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial

2015 ◽  
Vol 75 (6) ◽  
pp. 983-990 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Yoshiya Tanaka ◽  
Naoki Ishiguro ◽  
Hisashi Yamanaka ◽  
Toshiyuki Yoneda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Phase Ii ◽  
Bone Erosion ◽  
Therapeutic Option ◽  
Human Monoclonal Antibody ◽  
Joint Destruction ◽  
Japanese Patients ◽  
Apparent Difference ◽  
Mineral Density ◽  
Erosion Score

ObjectivesTo evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA).MethodsIn this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months.ResultsDenosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo.ConclusionsAddition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction.Trial registration numberJapicCTI-101263.

Effects of denosumab treatment on bone mineral density and joint destruction in patients with rheumatoid arthritis

2017 ◽  
Vol 36 (4) ◽  
pp. 431-438 ◽  
Author(s):  
Takeshi Mochizuki ◽  
Koichiro Yano ◽  
Katsunori Ikari ◽  
Kosei Kawakami ◽  
Ryo Hiroshima ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Mineral Density ◽  
Bone Mineral ◽  
Joint Destruction ◽  
Mineral Density ◽  
Denosumab Treatment

Remission achieved after 2 years treatment with low-dose prednisolone in addition to disease-modifying anti-rheumatic drugs in early rheumatoid arthritis is associated with reduced joint destruction still present after 4 years: an open 2-year continuation study

2008 ◽  
Vol 68 (4) ◽  
pp. 508-513 ◽  
Author(s):  
I Hafström ◽  
K Albertsson ◽  
A Boonen ◽  
D van der Heijde ◽  
R Landewé ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Low Dose ◽  
Joint Destruction ◽  
Joint Space ◽  
Mineral Density ◽  
Scoring Method ◽  
Sustained Effect ◽  
Radiological Damage ◽  
Disease Modifying ◽  
Hands And Feet

Objective:To evaluate if remission induced by low-dose prednisolone during the first 2 years of rheumatoid arthritis (RA) in the BARFOT glucocorticoid (GC) study had a sustained effect on radiological damage for a total of 4 years.Methods:A total of 150 of 211 eligible patients with RA who had been randomised to the 7.5 mg prednisolone group (P) or no prednisolone group (NoP) in addition to the initial disease-modifying antirheumatic drugs were included. Radiographs of hands and feet were scored using the Sharp–van der Heijde scoring method. A patient was considered to be in remission if the 28-joint count disease activity score was <2.6.Results:Mean (SD) age was 53 (14) and 57 (12) years for the patients in the P and NoP groups, respectively. 64% were female, 64% rheumatoid factor positive, and disease duration at baseline was 6 months. At 2 years the proportion of patients in remission in the P and NoP groups was 55 vs 30%, p = 0.003. Longitudinal analysis showed that over the entire course of the disease, patients on prednisolone had a higher probability of being in remission. Patients in remission at 2 years, compared with those not in remission, had significantly lower total Sharp score, erosion score and joint space narrowing score at 2 and 4 years. The changes in bone mineral density during the 4 years did not differ between those in remission and those with active disease, and were similar in the two treatment groups.Conclusions:Prednisolone 7.5 mg daily in addition to disease-modifying anti-rheumatic drugs increases the rate of remission in patients with early RA, which has a beneficial and sustained effect on radiological damage.

scholarly journals Effect of denosumab switched from bisphosphonates in preventing joint destruction in postmenopausal rheumatoid arthritis patients with anti-cyclic citrullinated peptide antibodies

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yu Mori ◽  
Takuya Izumiyama ◽  
Hiroaki Kurishima ◽  
Masayuki Kamimura ◽  
Kazuyoshi Baba ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Osteoporosis Treatment ◽  
Joint Space ◽  
Cyclic Citrullinated Peptide ◽  
Significant Difference ◽  
Modified Total Sharp Score ◽  
Denosumab Treatment ◽  
Citrullinated Peptide

Abstract Introduction This study aimed to determine the effects of denosumab treatment on the joint destruction of Japanese females with rheumatoid arthritis (RA) and anti-cyclic citrullinated peptide (CCP) antibodies. Materials and methods This retrospective longitudinal study included 56 patients treated with denosumab and 50 patients treated with bisphosphonate. All participants were positive for anti-CCP antibodies. All patients also had a history of osteoporosis treatment with bisphosphonate, which was either continued or switched to 60 mg of subcutaneous denosumab injection every 6 months. To assess the progression of joint destruction, hand and foot radiographs were taken, and changes in modified total Sharp score (mTSS), erosion score (ERO), and joint space narrowing score (JSN) were evaluated at 12 months and 24 months. The changes in BMD of the lumbar spine and hip were also assessed at 12 months. Results At 12 months, there were significant differences in the change of ERO (p = 0.015) and mTSS (p = 0.01). Similarly, there were significant differences in the change of ERO (p = 0.013) and mTSS (p = 0.003) at 24 months. In contrast, no significant difference was observed in the changes of JSN and clinical parameters. There were significant differences in the changes in BMD in the femoral neck (p = 0.011) and total hip (p = 0.012). Conclusion Denosumab treatment might be effective for the inhibition of bone erosion progression in the patients with RA, and it potentially contributes to the treatment of osteoporosis and prevention of destructive arthritis in patients with switching treatment from bisphosphonate.

scholarly journals Effect of denosumab switched from bisphosphonates in preventing joint destruction in postmenopausal rheumatoid arthritis patients with anti-cyclic citrullinated peptide antibodies

2021 ◽  
Author(s):  
Yu Mori ◽  
Takuya Izumiyama ◽  
Hiroaki Kurishima ◽  
Masayuki Kamimura ◽  
Kazuyoshi Baba ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Osteoporosis Treatment ◽  
Joint Space ◽  
Cyclic Citrullinated Peptide ◽  
Significant Difference ◽  
Modified Total Sharp Score ◽  
Denosumab Treatment ◽  
Citrullinated Peptide

Abstract Introduction: This study aimed to determine the effects of denosumab treatment on the joint destruction of Japanese females with rheumatoid arthritis (RA) and anti-cyclic citrullinated peptide (CCP) antibodies. Materials and Methods: This retrospective longitudinal study included 56 patients treated with denosumab and 50 patients treated with bisphosphonate. All participants were positive for anti-CCP antibodies. All patients also had a history of osteoporosis treatment with bisphosphonate, which was either continued or switched to 60 mg of subcutaneous denosumab injection every 6 months. To assess the progression of joint destruction, hand and foot radiographs were taken, and changes in modified total Sharp score (mTSS), erosion score (ERO) and joint space narrowing score (JSN) were evaluated at 12 months and 24 months. The changes in BMD of the lumbar spine and hip were also assessed at 12 months. Results: At 12 months, there were significant differences in the change of ERO (p = 0.015) and mTSS (p = 0.01). Similarly, there were significant differences in the change of ERO (p = 0.013) and mTSS (p = 0.003) at 24 months. In contrast, no significant difference was observed in the changes of JSN and clinical parameters. There were significant differences in the changes in BMD in the femoral neck (p = 0.011) and total hip (p = 0.012).Conclusion: Denosumab treatment might be effective for the inhibition of bone erosion progression in the patients with RA, and it potentially contributes to the treatment of osteoporosis and prevention of destructive arthritis in patients with switching treatment from bisphosphonate.

scholarly journals Effect of Denosumab in Preventing Joint Destruction in Rheumatoid Arthritis With Anti-Cyclic Citrullinated Peptide Antibodies

2020 ◽  
Author(s):  
Yu Mori ◽  
Takuya Izumiyama ◽  
Hiroaki Kurishima ◽  
Masayuki Kamimura ◽  
Kazuyoshi Baba ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Osteoporosis Treatment ◽  
Joint Space ◽  
Cyclic Citrullinated Peptide ◽  
Significant Difference ◽  
Modified Total Sharp Score ◽  
Denosumab Treatment ◽  
Citrullinated Peptide

Abstract Introduction: This study aimed to determine the effects of denosumab treatment on the joint destruction of Japanese females with rheumatoid arthritis (RA) and anti-cyclic citrullinated peptide (CCP) antibodies. Materials and Methods: This retrospective longitudinal study included 56 patients treated with denosumab and 50 patients treated with bisphosphonate. All participants were positive for anti-CCP antibodies. All patients also had a history of osteoporosis treatment with bisphosphonate, which was either continued or switched to 60 mg of subcutaneous denosumab injection every 6 months. To assess the progression of joint destruction, hand and foot radiographs were taken, and changes in modified total Sharp score (mTSS), erosion score (ERO) and joint space narrowing score (JSN) were evaluated at 12 months and 24 months. The changes in BMD of the lumbar spine and hip were also assessed at 12 months. Results: At 12 months, there were significant differences in the change of ERO (p = 0.015) and mTSS (p = 0.01). Similarly, there were significant differences in the change of ERO (p = 0.013) and mTSS (p = 0.003) at 24 months. In contrast, no significant difference was observed in the changes of JSN and clinical parameters. There were significant differences in the changes in BMD in the femoral neck (p = 0.011) and total hip (p = 0.012).Conclusion: Denosumab treatment was effective for the inhibition of bone erosion progression, and it contributes to the treatment of osteoporosis and prevention of destructive arthritis in patients with RA.

scholarly journals Effects of denosumab in Japanese rheumatoid arthritis patients treated with conventional anti-rheumatic drugs: 36-month extension of a phase 3 study

2021 ◽  
pp. jrheum.201376
Author(s):  
Yoshiya Tanaka ◽  
Tsutomu Takeuchi ◽  
Satoshi Soen ◽  
Hisashi Yamanaka ◽  
Toshiyuki Yoneda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Type I Collagen ◽  
Joint Destruction ◽  
Term Treatment ◽  
Drug Discontinuation ◽  
Type I ◽  
Mineral Density ◽  
Phase 3 ◽  
Long Term Treatment

Objective To evaluate safety and efficacy of long-term denosumab 60 mg every 6 (Q6M) or 3 months (Q3M) in rheumatoid arthritis (RA) patients. Methods This 12-month, randomised, double-blind, placebo-controlled, multicentre phase 3 trial with an open-label extension period from 12 to 36 months (DESIRABLE) enrolled Japanese RA patients treated with placebo for 12 months then denosumab Q6M (P/Q6M) or denosumab Q3M (P/Q3M); denosumab Q6M for 36 months (Q6M/Q6M); or denosumab Q3M for 36 months (Q3M/Q3M). Efficacy was assessed by van der Heijde modified total Sharp (mTSS), bone erosion (ES), and joint space narrowing (JSN) scores. Results Long-term treatment better maintained mTSS and ES suppression in the P/Q3M and Q3M/Q3M versus P/Q6M and Q6M/Q6M groups; changes from baseline in total mTSS at 36 months were 2.8 (standard error 0.4), 1.7 (0.3), 3.0 (0.4), and 2.4 (0.3), respectively; corresponding changes in ES were 1.3 (0.2), 0.4 (0.2), 1.4 (0.2), and 1.1 (0.2). No JSN effect was observed. Bone mineral density consistently increased in all groups after denosumab initiation, regardless of concomitant glucocorticoid administration. Serum C-telopeptide of type I collagen decreased rapidly at 1-month post-denosumab administration (both in the initial 12- month [Q3M, Q6M groups] and long-term treatment [P/Q3M, P/Q6M groups] phases). Adverse event incidence leading to study drug discontinuation was similar across treatment groups. Conclusion Denosumab treatment maintained inhibition of progression of joint destruction up to 36 months. Based on effects on ES progression, higher dosing frequency at an earlier treatment stage may be needed to optimise treatment. Denosumab was generally well tolerated.

scholarly journals The therapeutic effect to eldecalcitol + bisphosphonate is superior to bisphosphonate alone in the treatment of osteoporosis: a meta-analysis

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Zaoqian Zheng ◽  
Jinyu Luo
Keyword(s):  
Therapeutic Effect ◽  
Meta Analysis ◽  
Osteoporosis Treatment ◽  
Cochrane Library ◽  
Mineral Density ◽  
Random Effects Models ◽  
Online Databases ◽  
Metabolic Bone ◽  
Hip Bmd ◽  
Mean Differences

Abstract Background Osteoporosis is a metabolic bone disease. Bisphosphonate (BP) and eldecalcitol (ELD) are two clinical first-line drugs for osteoporosis patients. However, the effect of ELD + BP vs. BP alone on osteoporosis treatment is still unclear. The present meta-analysis was conducted to evaluate the different therapeutic effect of BP + ELD vs. BP alone in osteoporosis treatment. Methods Eligible documents that selected from online databases including PubMed, Embase, and Cochrane Library were included in this study (updated to March 3, 2020). The quality assessment of the included studies was based on the guidelines of Cochrane. Meta-analysis was performed according to criteria such as intervention plan and outcome. The indicators including bone mineral density (BMD) in all enrolled studies were included in the current analysis. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Then, heterogeneity analysis was performed based on Cochran’s Q test and I2 statistics. Results A total of 4 studies (456 cases) with high quality were enrolled in this study. The effect of ELD + BP was superior to BP alone based on indicators including femoral neck BMD (FN-BMD) and total hip BMD (TH-BMD) in patients with followed up ≤ 6 months. Moreover, the effect of ELD + BP was superior to BP alone based on lumbar spine BMD (LS-BMD) in patients with 12 months followed up. Conclusion Therapeutic effect of ELD + BP was superior to BP alone in osteoporotic patients based on the influence of BMD.

scholarly journals Relation between Hand Bone Mineral Density, Degree of Joint Destruction, and Hand Function in Adults Rheumatoid Arthritis Patients

2021 ◽  
Vol 2 (3) ◽  
pp. 116-121
Author(s):  
Aya N. Abdelrafee ◽  
Mohamed G. E. Zaki ◽  
Abeer K. El Zohiery ◽  
Manar A. Azab
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Mineral Density ◽  
Bone Mineral ◽  
Hand Function ◽  
Joint Destruction ◽  
Pinch Strength ◽  
Dominant Hand ◽  
Mineral Density ◽  
X Ray ◽  
Hand Disability

Background: Rheumatoid Arthritis [RA] is a chronic systemic disease that affects the functional capacity of the hand due to inflammatory arthritis and joint destruction. RA patients have difficulties with everyday life activities and daily living activities. The prevalence of osteoporosis is estimated to be about twice that of the general population. Dual-energy X-ray absorptiometry (DEXA) is the most precise tool for detecting loss in bone mineral density in RA. Aim of the study: This study aims to investigate the relation between generalized bone mineral density (BMD) and each of hand joint destruction and hand function in order to find out its possible role in assessment of rheumatoid hand disability. Patients and Methods: Fifty patients diagnosed as RA based on the 2010 ACR Rheumatoid Arthritis Classification Criteria were included in this study. All patients were subjected to the following scores: Duruöz Hand Index (DHI), Grip Ability Test (GAT), Grip strength test, and Pinch strength tests for assessing the function of the dominant hand of each patient. The participants were also subjected to plain x-ray evaluated by van der Heijde-modified total Sharp score (vdH-S) to assess the damage of the joints of the dominant hand, and Dual-energy X-ray absorptiometry (DEXA) to assess the Bone Mineral Density. Results: The current study showed that wrist BMD was correlated with grip strength, pinch strength, GAT, and van der Heijde modified sharp score of the dominant hand. Moreover, X-ray joint findings were significantly correlated with each of total grip ability test, grip strength, and pinch strength as the hand disability manifested more with joint damage. Conclusion: In conclusion, Osteoporosis, hand function, and joint damage in RA are correlated suggesting related pathophysiological mechanisms. The Severity of RA could be related to osteoporosis as well as joint destruction and hand disability.

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