Background: Osteoporosis (OP) is frequent complication identified in patients with rheumatoid arthritis (RA). Effective treatment must be provided to treat OP in RA (RAOP). Denosumab (DMB) is one of the promising drugs that are currently being used for the treatment of RAOP. We reported the results of 12-month DMB treatment for RAOP as part of Japanese multicenter registry study (TBCR-BONE) in EULAR2016 [1]. Recently, a treatment goal of OP was reported by the American Society for Bone and Mineral Research and the National Osteoporosis Foundation (ASBMR-NOF) working group [2]. This report advocated that the goal of treatment is a T-score of >-2.5 at the femoral neck, total hip (TH) or lumbar spine (LS) on DXA if the primary reason for starting treatment was a T-score of ≤-2.5 at the abovementioned skeletal sites. The working group noted that it was reasonable to expect that initial treatment should offer at least a 50% chance of achieving the treatment goal within 3 to 5 years of initiating therapy. We have reported the achievement rates of treatment goal in RAOP with 3-year DMB treatment on RAOP in EULAR2019 [3].

Objectives: The aim of this retrospective study was to evaluate whether 5-year DMB treatment can achieve treatment goal of OP using data from TBCR-BONE.

Methods: The study included 46 female patients who had completed 5-year DMB treatment. The LS-BMD analysis included 22 patients with a baseline (BL) LS-BMD T-score of ≤ -2.5. The TH-BMD analysis included 29 patients with a BL TH-BMD T-score of ≤ -2.5. Similar to clinical setting in Japan, 60mg of DMB was administered once every 6 months with a vitamin D3 supplement. BL characteristics, change in T-score over time, and achievement of the treatment goal (T-score>-2.5) were evaluated.

Results: BL characteristics of the 46 female patients included: mean age of 69.1 years and RA duration of 16 years. Prednisolone was administered to 37% of the patients. In the LS-BMD analysis, T-scores improved significantly; the mean value at BL was −3.4, which increased to −3.0 at 1 year, −2.6 at 3 years, and ultimately to −2.5 at 5 years. The fraction of patients who achieved the treatment goal was as follows: 36.4% at 1 year, 40.9% at 2 years, 45.5% at 3 years, 50.0% at 4 years, and 54.5% at 5 years ( Fig. 1A ). The patients who achieved this treatment goal were those who had a significantly lower risk of fracture at BL as determined by FRAX (17.9% vs. 32.2%, p = 0.044), who had significantly higher BL serum TRACP-5b level (572.8 vs. 401.0: p = 0.03), and who had significantly better BL LS-BMD T-scores (−3.0 vs. −3.9, p < 0.01) than the nonachievers. In the TH-BMD analysis, T-scores improved significantly; the mean value at BL was −3.0, and it increased to −3.0 at 1 year, −2.7 at 3 years, and reached −2.7 at 5 years. The fraction of patients who achieved the treatment goal was as follows: 20.7% at 1 year, 31.0% at 2 years, 34.5% at 3 years, 31.0% at 4 years, and 37.9% at 5 years ( Fig. 1 B ). The patients who achieved this treatment goal were those who had significantly better BL TH-BMD T-scores (−2.7 vs. −3.2: p < 0.01) than the nonachievers. Cut-off values at BL for achievement of the treatment goal determined using ROC analysis were −3.1 for the LS-BMD (sensitivity 83.3%, specificity 90.0%) and −2.85 for the TH-BMD (sensitivity 100.0%, specificity 81.0%).

Conclusion: The results of this study suggested that achievement of the treatment goal was comparatively easy for those with LS-BMD loss; however, it was comparatively difficult for those with TH-BMD loss. Early initiation or longer duration of DMB therapy may be necessary to improve achievement rates. Likewise, other agents, such as romosozumab, may be considered for those with significant TH-BMD loss.

REFERENCES:

[1]Hirano et al. Ann Rheum Dis 2016; 75 (Suppl 2): 94

[2]Cummings et al. J Bone Miner Res 2017; 32: 3-10

[3]Hirano et al. Ann Rheum Dis 2019; 78 (Suppl 2): A940

Disclosure of Interests: Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Yasuhide Kanayama: None declared, Hironobu Kosugiyama: None declared, Naoki Ishiguro Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi-Sankyo, Eisai, Kaken, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and Zimmer Biomet, Consultant of: Ono, Speakers bureau: Astellas, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, and Taisho Toyama, Toshihisa Kojima Grant/research support from: Chugai, Eli Lilly, Astellas, Abbvie, and Novartis, Consultant of: AbbVie, Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda