Identifying the preferable rheumatoid arthritis subgroups for intervention with the anti-RANKL antibody denosumab to reduce progression of joint destruction

RMD Open, vol. 6, pp. e001249

Abstract

OBJECTIVES: To clarify which rheumatoid arthritis (RA) patients benefit most from the anti-receptor activator of nuclear factor-κB ligand antibody denosumab to reduce the progression of joint destruction. METHODS: We pooled patient data from the 12-month, double-blind, placebo-controlled DRIVE (phase II) and DESIRABLE (phase III) studies. In DRIVE, concomitant treatment was limited to methotrexate, salazosulfapyridine and bucillamine. In DESIRABLE, patients could receive any disease-modifying antirheumatic drug. RA patients were randomised to denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or placebo. Efficacy was assessed by van der Heijde-modified total Sharp score (mTSS), bone erosion score (ES) and joint space narrowing score (JSNS). Change in mTSS was assessed in subgroups stratified by risk factors for radiographic damage if the interaction factor was significant. RESULTS: The pooled analysis included 909 patients. Denosumab reduced worsening of mTSS (mean (SD)) at 12 months in the Q6M (0.88 (3.30), p=0.0024) and Q3M (0.66 (2.16), p=0.0002) groups versus placebo (1.50 (3.73)). This reduction in mTSS progression was due to the change in ES (Q6M, 0.44 (1.89), p=0.0006; Q3M, 0.20 (0.86), p<0.0001) versus placebo (0.98 (2.54)); no effect was observed on JSNS. Anti-cyclic citrullinated peptide (CCP) antibodies, glucocorticoid use and baseline ES showed a significant interaction. Denosumab was particularly effective in patients who were anti-CCP antibody positive (p<0.05). Changes in mTSS versus placebo were observed in all denosumab dose groups, regardless of glucocorticoid use and baseline ES. CONCLUSIONS: Denosumab broadly reduced the progression of joint destruction in RA patients with risk factors for radiographic damage such as especially anti-CCP antibody positivity.

Authors 12

1. Yoshiya Tanaka corresponding

   University of Occupational and Environmental Health Japan

   Affiliation as printed

   First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan

2. Satoshi Soen

   Kindai University Nara Hospital

   Affiliation as printed

   Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma, Japan

3. Naoki Ishiguro

   Nagoya University

   Affiliation as printed

   Department of Orthopaedics, Nagoya University Graduate School of Medicine, Aichi, Japan

4. Hisashi Yamanaka

   Sanno Medical Center

   Affiliation as printed

   Director of Rheumatology, Sanno Medical Center, Tokyo, Japan

5. Toshiyuki Yoneda

   The University of Osaka

   Affiliation as printed

   Department of Biochemistry, Osaka University Graduate School of Dentistry, Osaka, Japan

6. Sakae Tanaka

   The University of Tokyo

   Affiliation as printed

   Department of Orthopaedic Surgery, The University of Tokyo, Tokyo, Japan

7. Takeshi Ohira

   Daiichi-Sankyo (Japan)

   Affiliation as printed

   Clinical Development Department, Daiichi Sankyo Co Ltd, Tokyo, Japan

8. Takaya Nitta

   Daiichi-Sankyo (Japan)

   Affiliation as printed

   Clinical Development Department, Daiichi Sankyo Co Ltd, Tokyo, Japan

9. Naoki Okubo

   Daiichi-Sankyo (Japan)

   Affiliation as printed

   Data Intelligence Department, Daiichi Sankyo Co Ltd, Tokyo, Japan

10. Harry K. Genant

    University of California, San Francisco

    Affiliation as printed

    Departments of Radiology, University of California San Francisco, California, USA

11. Désirée M F M van der Heijde Aachen Department of Rheumatology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands

12. Tsutomu Takeuchi

    Keio University

    Affiliation as printed

    Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan