Session Information
Date: Monday, November 6, 2017
Title: Osteoporosis and Metabolic Bone Disease – Clinical Aspects and Pathogenesis
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Glucocorticoid (GC)-induced osteoporosis (GIOP) remains the most common secondary cause of osteoporosis. We previously demonstrated that denosumab (DMAb) significantly increased lumbar spine (LS) BMD more than risedronate (RIS) at 12 mos in GC-treated individuals. Here, we explored the effects of DMAb and RIS on LS BMD in predefined subgroups to determine whether these factors affected the treatment effect.
Methods: This was a phase 3, randomized, double-blind, double-dummy, active-controlled study to evaluate DMAb vs. RIS in GC-treated individuals for 24 mos. Eligible subjects were women and men ≥18 yrs receiving GC therapy at a dose ≥7.5 mg prednisone daily or its equivalent for ≥3 mos or <3 mos prior to screening (GC-continuing [GC-C] and GC-initiating [GC-I], respectively). All subjects <50 yrs were required to have a history of osteoporotic fracture. GC-C subjects ≥50 yrs were required to have a LS, total hip, or femoral neck T‑score ≤‒2.0; or a T-score ≤‒1.0 with a history of osteoporotic fracture. Subjects were randomized 1:1 to SC DMAb 60 mg every 6 mos or oral RIS 5 mg daily for 24 mos. Subjects were to receive daily calcium (≥1000 mg) and vitamin D (≥800 IU). Effect of DMAb vs. RIS with respect to percentage change from baseline in LS BMD at 12 mos was determined in the GC-C and GC-I subpopulations and in 7 predefined subgroups that may influence treatment effect (gender, race, age group, baseline BMD T‑score, geographic region, menopausal status, and baseline GC daily dose).
Results: A total of 795 subjects (505 GC-C and 290 GC-I) enrolled in the study. Baseline characteristics were balanced between treatment groups. As previously shown (Saag, ACR 2016), DMAb resulted in greater gains in LS BMD at 12 mos compared with RIS for both the GC-C and GC-I subpopulations (Table). Results from all of the subgroups consistently demonstrated a greater increase in LS BMD at mo 12 with DMAb compared with RIS. A significant quantitative interaction was observed only in the gender analysis in the GC-I subpopulation. However, non-significant qualitative interaction testing indicated that there was no evidence that the direction of the DMAb effect differed by gender in this subpopulation.
Conclusion: DMAb consistently increased BMD more than RIS at the LS at 12 mos across 7 different subgroups of GC-treated individuals. DMAb has the potential to become a better treatment option for patients newly initiating or continuing GC who are at increased risk for fracture.
Table. Difference in Lumbar Spine BMD Percentage Change From Baseline at Month 12 (GC-C and GC‑I Subpopulations)
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|
GC-C Subpopulation (N = 230 RIS / 228 DMAb)
|
GC-I Subpopulation (N = 133 RIS / 128 DMAb) |
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|
Difference (DMAb – RIS) |
Interaction P value Quantitative (Qualitative)
|
Difference (DMAb – RIS) |
Interaction P value Quantitative (Qualitative)
|
|
Overall Subpopulation |
2.2 (1.4, 3.0)* |
N/A |
2.9 (2.0, 3.9)* |
N/A |
|
Gender |
|
|||
|
Female |
2.4 (1.5, 3.3)* |
0.31 |
3.7 (2.5, 4.9)* |
0.018 (0.50) |
|
Male |
1.3 (–0.3, 2.9) |
1.2 (–0.4, 2.8) |
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|
Race |
|
|||
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Caucasian |
2.1 (1.2, 2.9)* |
0.46 |
2.9 (1.9, 3.8)* |
0.68 |
|
Not Caucasian |
2.5 (0.2, 4.8)* |
3.0 (–0.4, 6.3) |
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Age Group |
|
|||
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< 60 years |
1.9 (0.8, 3.1)* |
0.57 |
2.7 (0.6, 4.8)* |
0.57 |
|
≥ 60 years |
2.3 (1.2, 3.5)* |
3.1 (2.0, 4.2)* |
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|
Baseline LS T-score |
|
|||
|
≤ –2.5 |
2.4 (0.9, 3.9)* |
0.40 |
3.8 (1.5, 6.0)* |
0.081 |
|
> –2.5 |
2.0 (1.1, 2.9)* |
2.5 (1.5, 3.5)* |
||
|
Baseline LS T-score |
|
|||
|
≤ –1.0 |
2.2 (1.3, 3.2)* |
0.55 |
3.5 (2.2, 4.9)* |
0.18 |
|
> –1.0 |
1.3 (–0.2, 2.9) |
2.0 (0.7, 3.2)* |
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Geographic Region |
|
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Europe |
2.0 (1.0, 3.0)* |
0.46 |
3.2 (2.1, 4.3)* |
0.60 |
|
Non-Europe |
2.5 (1.1, 3.8)* |
2.6 (0.8, 4.3)* |
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|
Menopausal Status |
|
|||
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Premenopausal |
1.7 (–0.7, 4.1) |
0.47 |
6.3 (1.9, 10.7)* |
0.37 |
|
Postmenopausal |
2.4 (1.4, 3.4)* |
3.5 (2.2, 4.8)* |
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Baseline GC Daily Prednisone-equivalent Dose |
|
|||
|
7.5 – < 10 mg |
2.9 (1.7, 4.1)* |
0.37 |
3.1 (0.9, 5.4)* |
0.98 |
|
≥ 10 mg |
2.0 (1.0, 3.1)* |
2.9 (1.8, 4.0)* |
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|
N = Number of randomized subjects with a baseline and ≥ 1 postbaseline lumbar spine BMD measurement. *DMAb compared with RIS p < 0.05 |
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To cite this abstract in AMA style:
Saag K, Pannacciulli N, Geusens P, Adachi J, Lespessailles E, Malouf J, Messina O, Wang A, Wagman RB, Lems W. Effect of Denosumab Compared with Risedronate on Percentage Change in Lumbar Spine Bone Mineral Density at 12 Months in Subgroups of Glucocorticoid-Treated Individuals [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/effect-of-denosumab-compared-with-risedronate-on-percentage-change-in-lumbar-spine-bone-mineral-density-at-12-months-in-subgroups-of-glucocorticoid-treated-individuals/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-denosumab-compared-with-risedronate-on-percentage-change-in-lumbar-spine-bone-mineral-density-at-12-months-in-subgroups-of-glucocorticoid-treated-individuals/