POS0094 EFFECTS OF RANKL INHIBITION ON PROMOTING HEALING OF BONE EROSION IN RHEUMATOID ARTHRITIS USING HR-pQCT: A 2-YEAR, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
Authors: H. So, I. T. Cheng, S. L. Lau, E. Chow, T. Lam, V. W. Hung, E. Li, J. F. Griffith, V. W. Lee, L. Shi, J. Huang, Y. K. Kwok, I. C. Yim, T. K. LI, V. Lo, J. M. Lee, J. J. W. Lee, L. Qin, L. S. Tam
Journal: Annals of the Rheumatic Diseases (2021)

Background: Partial repair of bone erosions in rheumatoid arthritis (RA) is known from high-resolution peripheral quantitative computer tomography (HR-pQCT) studies in patients with moderate to high disease activity using biologics [1]. Whether RANKL inhibition by denosumab is efficacious in healing existing erosions in RA patients with low disease activity or in remission on conventional synthetic DMARDs is uncertain. Objectives: To evaluate the effects of denosumab on erosion healing at 2-4 metacarpophalangeal head as determined by HR-pQCT in patients with RA with stable disease. Methods: This was a randomized, placebo-controlled, double-blind study. RA patients with disease activity score 28 joints (DAS28) ≤5.1 were randomized (1:1) to subcutaneous denosumab 60 mg or placebo once every six months for 24 months. The primary outcome was erosion healing at MCP 2-4 on HR-pQCT at 12 months. The effects of denosumab on erosion and joint space parameters on HR-pQCT and radiographs, disease activity and health assessment questionnaire-disability index (HAQ-DI) were also examined. Results: At 24 months, HR-pQCT images were analyzed in 98 patients. Baseline demographic, clinical characteristics and imaging parameters were comparable between the two treatment groups (table 1). Seventeen patients in each group (placebo group: 17/52, 32.6%; denosumab group: 17/50, 34.0%) achieved sustained low disease activity (DAS28 ≤ 3.2) throughout the 24 months. At 12 months, changes in erosion parameters on HR-pQCT were similar between the two groups. At 24 months, new erosions (19% vs 9%, p=0.009) and erosion progression (34% vs 16%, p&lt;0.001) were more common in the placebo group than the denosumab group. Erosion healing was seen in a significantly higher proportion of patients in the denosumab group (20% vs 6%, p=0.045) at 24 months. The details of the changes in HR-pQCT erosion parameters are shown in figure 1. No significant differences in the changes in joint space parameters on HR-pQCT, van der Heijde-Sharp erosion score, DAS28 and HAQ-DI were observed between the two groups at 12 and 24 months. Table 1. Baseline clinical, demographic, disease activity parameters and medications Placebo (n=55) Denosumab (n=55) Total (n=110) Age 56.5 ± 7.1 57.2 ± 8.5 56.8 ± 7.8 Gender (Female) 47 (86) 41 (75) 88 (80) Disease duration (years) 8.5 ± 6.8 7.3 ± 6.9 7.9 ± 6.8 Rheumatoid factor positive 40 (72) 38 (69) 78 (71) ACPA positive 43 (78) 44 (80) 87 (79) DAS28-CRP 2.43 ± 0.83 2.6 ± 0.92 2.51 ± 0.88 DAS28-CRP&gt;3.2 8 (15) 13 (24) 21 (19) HAQ-DI (0-3) 0.31 ± 0.38 0.46 ± 0.47 0.39 ± 0.43 csDMARDs 49 (89) 52 (95) 101 (92) Combination csDMARDs 26 (47) 33 (60) 59 (54) Glucocorticoids 5 (10) 5 (9) 10 (9) vdH- Sharp erosion score 10.4 ± 18.4 8.9 ± 13.8 9.6 ± 16.2 vdH- Sharp JSN score 12.4 ± 17.7 11.5 ± 17.2 11.9 ± 17.4 Lumbar spine aBMD, g/cm 2 0.914 ± 0.147 0.930 ± 0.143 0.922 ± 0.145 Total hip aBMD, g/cm 2 0.837 ± 0.102 0.847 ± 0.146 0.841 ± 0.125 Femoral neck aBMD, g/cm 2 0.681 ± 0.099 0.695 ± 0.128 0.687 ± 0.114 Data are reported as mean ± SD or number (%). ACPA: Anti-cyclic citrullinated peptide antibody; DAS28: disease activity score 28; csDMARDs: conventional synthetic disease modifying anti-rheumatic drug. HAQ-DI: health assessment questionnaire disability index; vdH- Sharp score: Van der Heijde- Sharp score; aBMD: areal bone mineral density Conclusion: Although no differences in erosion parameters were observed at 12 months, denosumab was more efficacious than placebo in erosion repair on HR-pQCT after 24 months. References: [1]Finzel S, Rech J, Schmidt S, et al. Interleukin-6 receptor blockade induces limited repair of bone erosions in rheumatoid arthritis: a micro CT study. Ann Rheum Dis 2013;72:396-400. Figure 1. Changes in erosion parameters by HR-pQCT. (A) Percentage of patients with overall erosion healing; (B) Outcome of individual erosion with healing, progression and new erosion detected across study period; change in (C) mean erosion volume; (D) total erosion volume; (E) erosion width; (F) erosion depth and (G) marginal osteosclerosis per patient. Disclosure of Interests: Ho SO: None declared, Isaac T. Cheng: None declared, Sze-Lok Lau: None declared, Evelyn Chow: None declared, Tommy Lam: None declared, Vivian W Hung: None declared, Edmund Li: None declared, James F Griffith: None declared, Vivian WY Lee: None declared, Lin Shi: None declared, Junbin Huang: None declared, Yan Kitty Kwok: None declared, Isaac C Yim: None declared, Tena K. Li: None declared, Vincent Lo: None declared, Jolly M Lee: None declared, Jack Jock Wai Lee: None declared, Ling Qin: None declared, Lai-Shan Tam Grant/research support from: Grants from Novartis and Pfizer