Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four–Month Randomized, Double-Blind, Double-Dummy Trial

Kenneth G. Saag, Nicola Pannacciulli, Piet Geusens, Jonathan D. Adachi, Osvaldo D. Messina, Jorge Morales-Torres, Ronald Emkey, Peter W. Butler, Xiang Yin, Willem F. Lems

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. Methods: This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of −2.0 or less (or −1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. Results: Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24-month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. Conclusion: Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.
Original languageEnglish
Pages (from-to)1174-1184
JournalArthritis and Rheumatology
Volume71
Issue number7
DOIs
Publication statusPublished - 2019

Cite this

Saag, Kenneth G. ; Pannacciulli, Nicola ; Geusens, Piet ; Adachi, Jonathan D. ; Messina, Osvaldo D. ; Morales-Torres, Jorge ; Emkey, Ronald ; Butler, Peter W. ; Yin, Xiang ; Lems, Willem F. / Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four–Month Randomized, Double-Blind, Double-Dummy Trial. In: Arthritis and Rheumatology. 2019 ; Vol. 71, No. 7. pp. 1174-1184.
@article{9d3fbdc8160542028c15d60e6153081a,
title = "Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four–Month Randomized, Double-Blind, Double-Dummy Trial",
abstract = "Objective: Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. Methods: This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of −2.0 or less (or −1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. Results: Of 795 patients, 590 (74.2{\%}) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2{\%} versus 1.7{\%}, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1{\%} versus 0.0{\%} [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4{\%} versus 3.2{\%} [P < 0.001]; 24-month total hip: BMD increase of 2.9{\%} versus 0.5{\%} [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. Conclusion: Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.",
author = "Saag, {Kenneth G.} and Nicola Pannacciulli and Piet Geusens and Adachi, {Jonathan D.} and Messina, {Osvaldo D.} and Jorge Morales-Torres and Ronald Emkey and Butler, {Peter W.} and Xiang Yin and Lems, {Willem F.}",
year = "2019",
doi = "10.1002/art.40874",
language = "English",
volume = "71",
pages = "1174--1184",
journal = "Arthritis & rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "7",

}

Saag, KG, Pannacciulli, N, Geusens, P, Adachi, JD, Messina, OD, Morales-Torres, J, Emkey, R, Butler, PW, Yin, X & Lems, WF 2019, 'Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four–Month Randomized, Double-Blind, Double-Dummy Trial' Arthritis and Rheumatology, vol. 71, no. 7, pp. 1174-1184. https://doi.org/10.1002/art.40874

Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four–Month Randomized, Double-Blind, Double-Dummy Trial. / Saag, Kenneth G.; Pannacciulli, Nicola; Geusens, Piet; Adachi, Jonathan D.; Messina, Osvaldo D.; Morales-Torres, Jorge; Emkey, Ronald; Butler, Peter W.; Yin, Xiang; Lems, Willem F.

In: Arthritis and Rheumatology, Vol. 71, No. 7, 2019, p. 1174-1184.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four–Month Randomized, Double-Blind, Double-Dummy Trial

AU - Saag, Kenneth G.

AU - Pannacciulli, Nicola

AU - Geusens, Piet

AU - Adachi, Jonathan D.

AU - Messina, Osvaldo D.

AU - Morales-Torres, Jorge

AU - Emkey, Ronald

AU - Butler, Peter W.

AU - Yin, Xiang

AU - Lems, Willem F.

PY - 2019

Y1 - 2019

N2 - Objective: Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. Methods: This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of −2.0 or less (or −1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. Results: Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24-month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. Conclusion: Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.

AB - Objective: Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. Methods: This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of −2.0 or less (or −1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. Results: Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24-month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. Conclusion: Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85067689080&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30816640

U2 - 10.1002/art.40874

DO - 10.1002/art.40874

M3 - Article

VL - 71

SP - 1174

EP - 1184

JO - Arthritis & rheumatology

JF - Arthritis & rheumatology

SN - 2326-5191

IS - 7

ER -