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.

scholarly journals Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial

2019 ◽  
Vol 78 (7) ◽  
pp. 899-907 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Yoshiya Tanaka ◽  
Satoshi Soen ◽  
Hisashi Yamanaka ◽  
Toshiyuki Yoneda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Placebo Group ◽  
Structural Damage ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Mineral Density ◽  
Phase 3 ◽  
Double Blind ◽  
The Mean ◽  
Disease Modifying

ObjectiveTo evaluate the efficacy of denosumab in suppressing joint destruction when added to conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy in patients with rheumatoid arthritis (RA).MethodsThis was a multi-centre, randomised, double-blind, parallel-group, placebo-controlled phase 3 study in Japan. Patients with RA aged ≥20 years receiving csDMARDs were randomly assigned (1:1:1) to denosumab 60 mg every 3 months (Q3M), denosumab 60 mg every 6 months (Q6M) or placebo. The change in the modified total Sharp score (mTSS) and effect on bone mineral density (BMD) at 12 months was evaluated.ResultsIn total, 654 patients received the trial drugs. Denosumab groups showed significantly less progression of joint destruction. The mean changes in the mTSS at 12 months were 1.49 (95% CI 0.99 to 1.99) in the placebo group, 0.99 (95% CI 0.49 to 1.49) in the Q6M group (p=0.0235) and 0.72 (95% CI 0.41 to 1.03) in the Q3M group (p=0.0055). The mean changes in bone erosion score were 0.98 (95% CI 0.65 to 1.31) in the placebo group, 0.51 (95% CI 0.22 to 0.80) in the Q6M group (p=0.0104) and 0.22 (95% CI 0.09 to 0.34) in the Q3M group (p=0.0001). No significant between-group difference was observed in the joint space narrowing score. The per cent change in lumbar spine (L1–L4) BMD in the placebo, Q6M and Q3M groups were −1.03%, 3.99% (p<0.0001) and 4.88% (p<0.0001). No major differences were observed among safety profiles.ConclusionsDenosumab inhibits the progression of joint destruction, increases BMD and is well tolerated in patients with RA taking csDMARD.

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 FRI0550 CAN CYTOKINE GENE POLYMORPHISMS BE USEFUL FOR THE THERAPEUTIC CHOICE IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 876.2-877
Author(s):  
S. Tsujimoto ◽  
M. Shigesaka ◽  
A. Tanaka ◽  
Y. Ozaki ◽  
T. Ito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Gene Polymorphisms ◽  
Therapeutic Response ◽  
Bone Erosion ◽  
Japanese Patients ◽  
Cartilage Degradation ◽  
Cytokine Gene ◽  
Biological Dmards ◽  
Cytokine Gene Polymorphisms

Background:Rheumatoid arthritis (RA) is a common autoimmune disease. It is characterized by systemic synovitis with bone erosion and joint cartilage degradation(1). Production of autoantibody is important for autoimmune disease. Cytokines play crucial roles in its pathogenesis(2). SNP distribution varies between races. Few studies have examined SNP targeted at Japanese patients. The analysis of cytokine gene polymorphisms is important factor of pathophysiology and treatment.Objectives:This analysis was aimed to investigate the association between cytokine gene polymorphisms and autoantibody and therapeutic response in Japanese RA patients.Methods:This study subjects consisted of 100 RA patients and 50 healthy controls. We extracted data on patient sex, age, disease duration, rheumatoid factor (RF), anti cyclic citrullinated peptide (anti-CCP) antibody and therapeutic response including methotrexate (MTX) and biological DMARDs. Genomic DNA was isolated from peripheral blood, these were genotyped for TNFα, TGFβ1, IL-6, IL-10 and IFNγ polymorphisms. We analyzed these data using a chi-square test.Results:IL-10 (-819 C/T and -592 C/A) revealed that there were significant decrease in the frequency of IL-10 (-819) CC genotype and (-592) CC genotype as compared to controls in RA patients. Genotyping of IL-10 showed that there was significant decrease ACC/ACC genotype (Table 1).IFNγ (+874 A/T) revealed that there was significant decrease in the frequency of TT genotype as compared to controls (Table 1).No significant differences in TNFα, TGFβ1and IL-6 genotypes and alleles frequency were observed between RA patients and control.TGFβ1(+869 A/T) in patients with anti-CCP antibody positive revealed that there was significant decrease in the frequency of TT genotype as compared to patients with anti-CCP antibody negative (Table 2).No significant association between RF and any cytokine gene polymorphism.Analyzing cytokine gene polymorphisms could be useful for treatment with MTX and biological DMARDs.Table 1.Table 2.Conclusion:IL-10 (-819 C/T, -592 C/A) and IFNγ (+874 A/T) polymorphism might be related to RA in Japanese population. In addition, TGFβ1(+869 A/T) polymorphism might be associated with the production of anti-CCP antibody. These results suggest that the analyzing cytokine gene polymorphisms may offer promise as useful factors in the choice of treatment for Japanese RA patients.References:[1] Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010; 376: 1094–108.[2] McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007 Jun;7(6):429-42.Disclosure of Interests:None declared

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.

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

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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