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Effects of RANKL inhibition on promoting healing of bone erosion in rheumatoid arthritis using HR-pQCT: a 2-year, randomised, double-blind, placebo-controlled trial
  1. Ho So1,
  2. Isaac T Cheng1,
  3. Sze-Lok Lau1,
  4. Evelyn Chow1,
  5. Tommy Lam1,
  6. Vivian W Hung2,
  7. Edmund K Li1,
  8. James F Griffith3,
  9. Vivian W Lee4,
  10. Lin Shi3,
  11. Junbin Huang3,
  12. Kitty Yan Kwok5,
  13. Cheuk-Wan Yim6,
  14. Tena K Li1,
  15. Vincent Lo1,
  16. Jolie Lee7,
  17. Jack Jock-Wai Lee8,
  18. Ling Qin2,
  19. Lai-Shan Tam1
  1. 1 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  2. 2 Bone Quality and Health Centre of the Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  3. 3 Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  4. 4 School of Pharmacy, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  5. 5 Department of Medicine, Queen Elizabeth Hospital, Hong Kong, Hong Kong
  6. 6 Department of Medicine, Tseung Kwan O Hospital, Hong Kong, Hong Kong
  7. 7 Department of Medicine, Tai Po Hospital, Hong Kong, Hong Kong
  8. 8 Division of Biostatistics, The Jockey Club School of Public Health & Primary Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  1. Correspondence to Dr Lai-Shan Tam, Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong; lstam{at}cuhk.edu.hk

Abstract

Objective To evaluate the effects of denosumab on erosion healing at 2–4 metacarpophalangeal (MCP) head as determined by high-resolution peripheral quantitative CT (HR-pQCT) in patients with rheumatoid arthritis (RA) with stable disease.

Methods This was a randomised, placebo-controlled, double-blind study. Patients with RA with disease activity score 28 joints (DAS28) ≤5.1 were randomised (1:1) to subcutaneous denosumab 60 mg or placebo once every 6 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 analysed in 98 patients. One-third of the patients achieved sustained low disease activity throughout the study. 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 (18% vs 8%, p=0.019) 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. No significant changes in joint space parameters on HR-pQCT, van der Heijde-Sharp erosion score, DAS28 and HAQ-DI were observed in the two groups at 12 and 24 months.

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.

Trial registration number NCT03239080.

  • rheumatoid arthritis
  • biological therapy
  • therapeutics

Data availability statement

No data are available.

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Data availability statement

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors All authors critically revised the manuscript for important intellectual content. Specific roles included: study design (L-ST), data collection (HS, L-ST, EKL, JL, C-WY, TL, ITC, S-SL, EC, TL, VL), data analysis (ITC, S-SL, EC, JJ-WL, LS, JH), drafting of manuscript (HS, L-ST, JFG, LQ).

  • Funding The Health and Medical Research Fund Project No: 04152616.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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