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

Tsutomu Takeuchi, Yoshiya Tanaka, Satoshi Soen, Hisashi Yamanaka, Toshiyuki Yoneda, Sakae Tanaka, Takaya Nitta, Naoki Okubo, Harry K. Genant, Désirée Van Der Heijde

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: To 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). Methods: This 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. Results: In 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. Conclusions: Denosumab inhibits the progression of joint destruction, increases BMD and is well tolerated in patients with RA taking csDMARD.

Original languageEnglish
JournalAnnals of the rheumatic diseases
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Antirheumatic Agents
Anti-Idiotypic Antibodies
Rheumatoid Arthritis
Joints
Placebos
Bone
Antibodies
Bone Density
Minerals
Drug therapy
Erosion
Japan
Spine
Denosumab
Safety
Bone and Bones
Drug Therapy
Pharmaceutical Preparations

Keywords

  • denosumab
  • erosion
  • joint destruction
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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. / Takeuchi, Tsutomu; Tanaka, Yoshiya; Soen, Satoshi; Yamanaka, Hisashi; Yoneda, Toshiyuki; Tanaka, Sakae; Nitta, Takaya; Okubo, Naoki; Genant, Harry K.; Van Der Heijde, Désirée.

In: Annals of the rheumatic diseases, 01.01.2019.

Research output: Contribution to journalArticle

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title = "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",
abstract = "Objective: To 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). Methods: This 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. Results: In 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. Conclusions: Denosumab inhibits the progression of joint destruction, increases BMD and is well tolerated in patients with RA taking csDMARD.",
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T2 - A randomised, double-blind, placebo-controlled phase 3 trial

AU - Takeuchi, Tsutomu

AU - Tanaka, Yoshiya

AU - Soen, Satoshi

AU - Yamanaka, Hisashi

AU - Yoneda, Toshiyuki

AU - Tanaka, Sakae

AU - Nitta, Takaya

AU - Okubo, Naoki

AU - Genant, Harry K.

AU - Van Der Heijde, Désirée

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: To 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). Methods: This 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. Results: In 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. Conclusions: Denosumab inhibits the progression of joint destruction, increases BMD and is well tolerated in patients with RA taking csDMARD.

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KW - denosumab

KW - erosion

KW - joint destruction

KW - rheumatoid arthritis

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