Background: Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B ligand, which inhibits osteoclast differentiation, activation and survival, not only increases bone mineral density but also inhibits the progression of bone erosion in patients with rheumatoid arthritis (RA) ^1-3) . Therefore, denosumab have been preferably prescribed for patients with RA recently. The persistence with denosumab, which is administered subcutaneously once every 6 months, was reported higher than with oral bisphosphonates ⁴⁾ , and in the prospective cohort studies, the persistence rate for one year was reported to be 82-95% ^5-6) . However, there have been no report about the persistence in patients with RA treated with denosumab, moreover the reasons for discontinuation of denosumab.

Objectives: The aims of this single center retrospective cohort study were 1) to assess the persistence with denosumab in a routine clinical setting and 2) to identify the reasons of discontinuation in patients with RA. And we also reviewed the clinical outcomes of osteonecrosis of the jaw in patients with RA during denosumab treatment.

Methods: The present study is based on databases from our hospital, which include age, gender, date of injection of denosumab, as well as information on patients’ characteristics. Patients were included in this study when denosumab were newly started at our department during the period from June 1, 2013 and September 30, 2017. In this study, persistence was defined as patients with an interval between injections of no longer than 6 months plus 8 weeks. Patients were followed until censoring (death, transferring to another hospital) or the end of the study (August 3, 2018).

We investigated reasons for the discontinuation of denosumab. Major reasons for the discontinuation of denosumab were classified as adverse event, anxiety over adverse events, patient’s transfer or request, doctor’s careless lack of refilling an injection, and other reason.

We identified patients who had been diagnosed as osteonecrosis of the jaw, and demographic, pharmacological, and clinical data were collected from medical records.

Results: One hundred and seventy-five patients were identified. Kaplan–Meier analysis showed a slow decline of persistence after initiating denosumab therapy, dropping to 80.4 and 61.9 % after 1 and 2 years of follow-up. When analyzing the reason of discontinuation as adverse events, the persistence rate of denosumab was at 89.4, and 79.4% at 1, and 2 years of follow-up, respectively.

During 2-year period, 72 patients discontinued denosumab. A total of 27 adverse events occurred, of which five events were osteonecrosis of the jaw. The other reasons for adverse event included death in four, fracture in three, and so on. Six patients discontinued due to anxiety over dental adverse event. Thirteen patients were in doctor’s careless lack of refilling an injection

All five patients who were diagnosed as osteonecrosis of the jaw had received the treatment with prednisolone, and four were treated with biologic drugs. All patients stopped denosumab and switched to other drugs including teriparatide. All patients underwent surgical curettages of necrotic bone and cured.

Conclusion: Persistence of denosumab in patients with RA is comparable to that in postmenopausal women with osteoporosis. Dental screening and care should be important to continue denosumab treatment.

REFERENCES:

[1]Cohen SB. Arthritis Rheum . 2008;58:1299–1309.

[2]Takeuchi T. Ann Rheum Dis . 2019;78:899–907.

[3]Ebina K. Osteoporos Int . 2018;29:1627–1636.

[4]Hadji P. Osteoporos Int . 2016;27:2967–2978.

[5]Silverman SL. Arch Osteoporos . 2018;13:85. doi:10.1007/s11657-018-0491-z

[6]Hadji P. Osteoporos Int . 2015;26:2479–2489.

Disclosure of Interests: Shinichi Mizuki Speakers bureau: AbbVie, Asahi Kasei, Chugai, Eli Lilly, Janssen, Mitsubishi Tanabe, Ono, Tatsuya Kai: None declared, Koji Mishima: None declared, Hiroko Ikeuchi: None declared, Kensuke Oryoji: None declared