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POS0094 (2021)
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
H. So1, I. T. Cheng1, S. L. Lau1, E. Chow1, T. Lam1, V. W. Hung2, E. Li1, J. F. Griffith3, V. W. Lee4, L. Shi3, J. Huang3, Y. K. Kwok5, I. C. Yim6, T. K. LI1, V. Lo1, J. M. Lee7, J. J. W. Lee8, L. Qin2, L. S. Tam1
1The Chinese University of Hong Kong, Medicine and Therapeutics, Hong Kong, Hong Kong (SAR)
2The Chinese University of Hong Kong, Orthopedics & Traumatology, Hong Kong, Hong Kong (SAR)
3The Chinese University of Hong Kong, Imaging & Interventional Radiology, Hong Kong, Hong Kong (SAR)
4The Chinese University of Hong Kong, School of Pharmacy, Hong Kong, Hong Kong (SAR)
5Queen Elizabeth Hospital, Medicine, Hong Kong, Hong Kong (SAR)
6Tseung Kwan O Hospital, Medicine, Hong Kong, Hong Kong (SAR)
7Tai Po Hospital, Medicine and Geriatrics, Hong Kong, Hong Kong (SAR)
8The Chinese University of Hong Kong, The Jockey Club School of Public Health & Primary Care, Hong Kong, Hong Kong (SAR)

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<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.

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>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.

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

Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 257
Session: Rheumatoid arthritis - prognosis, predictors and outcome (Poster Tours)