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POS0687 (2022)
INHIBITION OF BONE EROSION, DETERMINED BY HIGH-RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (HR-pQCT), IN RHEUMATOID ARTHRITIS PATIENTS RECEIVING A CONVENTIONAL SYNTHETIC DMARD (csDMARD) PLUS DENOSUMAB VS csDMARD THERAPY ALONE: RESULTS OF AN OPEN-LABEL, RANDOMIZED, PARALLEL-GROUP STUDY
N. Iwamoto1, K. Chiba2, S. Sato3, K. Shiraishi2, K. Watanabe2, N. Ohki4, A. Okada5, T. Koga1, M. Kobayashi6, K. Saito6, N. Okubo7, A. Kawakami1
1Nagasaki University Graduate School of Biomedical Sciences, Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki, Japan
2Nagasaki University Graduate School of Biomedical Sciences, Department of Orthopedic Surgery, Nagasaki, Japan
3Nagasaki University Hospital, Clinical Research Center, Nagasaki, Japan
4Nagasaki University Graduate School of Biomedical Sciences, Department of Radiological Sciences, Nagasaki, Japan
5Japanese Red Cross Nagasaki Genbaku Hospital, Department of Rheumatology, Nagasaki, Japan
6Daiichi Sankyo Co., Ltd., Primary Medical Science Department, Medical Affairs Division, Tokyo, Japan
7Daiichi Sankyo Co., Ltd., Data Intelligence Department, Digital Transformation Management Division, Tokyo, Japan

Background: Denosumab, a human IgG2 monoclonal antibody with high affinity for RANKL, is approved for treatment of bone erosion (ER) in patients with RA, based on the results of clinical trials. However, its effectiveness in combination with conventional therapy in RA patients has not been fully investigated in clinical practice.


Objectives: This exploratory study aimed to compare, in patients receiving conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) for treatment of RA, the effectiveness of combined use of csDMARD and denosumab vs csDMARD alone, in terms of inhibition of ER determined by HR-pQCT.


Methods: Detail protocol of this open-label, randomized, parallel-group study has been published previously. 1 RA patients with moderate or low disease activity and progressive ER were eligible, and were randomly assigned to receive denosumab in addition to the csDMARD (denosumab) group or to continued use of the csDMARD alone (csDMARD) group. Denosumab was administered every 6 months during the 12-month study period. The primary endpoint was change in ER-depth at the second and third metacarpal bones, determined by HR-pQCT at month 6. For the primary endpoint, a linear mixed effect model analysis was performed using treatment group, sex, anti-cyclic citrullinated peptide (CCP) antibody (positive vs negative), and baseline disease activity (DAS28-ESR) as fixed effects, patients as random effects, and baseline values as covariates. For extension data, measurement time-point and the interaction between treatment group and measurement time-point was further added as fixed effects. The adverse events (AEs) were recorded.


Results: A total of 46 patients were randomized to denosumab and csDMARD groups (both N=23), and baseline characteristics were similar between both groups. Although the difference was not significant, the estimate mean (95%CI) change of ER-depth at month 6 from baseline as the primary endpoint was −0.57 (−1.52, 0.39) in the denosumab group vs −0.22 (−0.97, 0.53) in the csDMARD group, respectively. At months 6 and 12, ER-depth, -width, and -volume (extension data) were numerically lower in the denosumab group than in the csDMARD group ( Table 1 ). Compared with patients in the csDMARD group, those in the denosumab group had significantly higher volumetric bone mineral density (vBMD) at month 12. AEs were reported in 12 (52.2%) and 13 (56.5%) of patients in the denosumab and csDMARD groups, respectively. The most common AEs of denosumab groups was hypocalcemia (reported in 4), and all the events were causally related with denosumab. Serious AEs were reported in 1 (4.3%) and 2 (8.7%) of patients in the denosumab and csDMARD groups, and which were not related to treatment drug.

ER and microstructure in denosumab group vs csDMARD group

Month Denosumab group (n=21) csDMARDs group (n=22) Difference (Denosumab- csDMARDs)
n1 Estimate Means [95%CI] n1 Estimate Means [95%CI] Estimate Means [95%CI]
ER-depth 6 17 −0.46 [−1.31, 0.39] 25 −0.20 [−0.89, 0.49] −0.27 [−0.86, 0.32]
12 17 −0.56 [−1.41, 0.29] 22 −0.20 [−0.90, 0.49] −0.35 [−0.95, 0.24]
ER-width 6 17 −0.26 [−1.10, 0.57] 25 −0.06 [−0.73, 0.61] −0.20 [−0.81, 0.40]
12 17 −0.27 [−1.10, 0.56] 22 −0.03 [−0.70, 0.64] −0.24 [−0.85, 0.38]
ER-volume 6 16 −6.21 [−23.89, 11.46] 24 −1.71 [−16.07, 12.66] −4.51 [−16.67, 7.65]
12 17 −6.25 [−23.94, 11.44] 21 −3.18 [−17.56, 11.20] −3.07 [−15.32, 9.17]
vBMD 6 42 6.41 [2.78, 10.03] 44 2.46 [−1.33, 6.24] 3.95 [−0.05, 7.94]
12 38 9.20 [5.46, 12.95] 42 3.66 [−0.15, 7.46] 5.55 [1.46, 9.63]*

These were extension data.

This is the efficacy analysis set which excluded 3 patients from the full analysis set.

*; p<0.01

n, number of patients; n1, number of measurement points


Conclusion: Our results suggest that adding denosumab to csDMARD therapy may help prevent ER, promote ER repair, and improve bone microstructure.


REFERENCES:

[1]Iwamoto N, et al ., Trials. 2019;20(1):1–8.


Disclosure of Interests: Naoki Iwamoto Speakers bureau: Daiichi Sankyo Co., Ltd., Grant/research support from: Daiichi Sankyo Co., Ltd., Ko Chiba Speakers bureau: Daiichi Sankyo Co., Ltd., Shuntaro Sato: None declared, Kazuteru Shiraishi: None declared, Konosuke Watanabe: None declared, Nozomi Ohki: None declared, Akitomo Okada: None declared, Tomohiro Koga: None declared, Makiko Kobayashi Employee of: Daiichi Sankyo Co., Ltd. (retired at submission), Kengo Saito Employee of: Daiichi Sankyo Co., Ltd., Naoki Okubo Employee of: Daiichi Sankyo Co., Ltd., Atsushi Kawakami Speakers bureau: Daiichi Sankyo Co., Ltd., Grant/research support from: Daiichi Sankyo Co., Ltd.

Citation: , volume 81, supplement 1, year 2022, page 622
Session: Rheumatoid arthritis - non biologic treatment and small molecules (POSTERS only)