POS0730 DECREASED RISK OF OSTEONECROSIS OVER TIME IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS USING JAPANESE HEALTH INSURANCE DATABASE
Authors: R. Sakai, E. Tanaka, M. Yamagishi, M. Majima, M. Harigai
Journal: Annals of the Rheumatic Diseases (2021)

Background: In patients with systemic lupus erythematosus (SLE), prevalence of osteonecrosis (ON) was 20–40% 1 , and 4–10 times higher risk of ON than the general population was observed 2,3 . Because ON can influence patients’ physical activity and quality of life, it is essential for rheumatologists to manage ON appropriately. Recently, medications such as mycophenolate mofetil (MMF) and hydroxychloroquine (HCQ) were approved for SLE in Japan. Considering the changes in treatments for SLE over time, it is clinically important to investigate the risk and risk factors of ON in patients with the disease. However, to date, only evidence is found in the literature. Objectives: To estimate incidence rate (IR) and identify risk factors of ON in patients with SLE using a Japanese health insurance database. Methods: This retrospective longitudinal population-based study was conducted using claims data provided by Medical Data Vision Co., Ltd (Tokyo, Japan). We defined individuals as SLE cases if they met all of the following: 1) having at least one ICD10 code (M321 or M329); 2) having at least one prescription of oral corticosteroids (CS), methylprednisolone (mPSL) pulse therapy, immunosuppressive drugs (IS) (azathioprine, mizoribine, tacrolimus, MMF, cyclophosphamide, methotrexate), biologics (belimumab, rituximab) or HCQ between January 2010 and January 2017; 3) being 16 years old or over. The start of observation was defined by the first month in which cases met all of the above criteria. Patients were followed until the earliest of date of first ON, date of loss of follow-up, or the end of follow-up (December 2017). ON was defined when patients had at least one ICD code (M87.0, M87.1, M87.2, M87.3, M87.8, M87.9, M90.5) during the observation period. Patients were excluded if they had a previous diagnosis of ON during the first 3 months of the observation period. We defined baseline characteristics using the data in the month of starting observation, and calculated incidence rate (IR) in each year, adjusted relative risk (RR [95% CI]) of ON using a Poisson regression model, and adjusted odds ratio (OR [95% CI]) of risk factors of ON after adjusting for age and sex at baseline, and medications and comorbidities during the observation period using a logistic regression model. Results: In this study, 16,386 cases were included. The median age was 55 years and 81.3% were female. Median observation period was 33 months, and total observation period was 47,138 patient-years (PY). IR/1,000 PY of ON in each year from 2010 to 2017 was 13.2, 10.6, 11.0, 13.3, 13.1, 9.8, 8.5, and 7.3, respectively. Adjusted RR in each year from 2011 to 2017 compared to 2010 was 0.5 [0.2–1.4], 0.3 [0.1–0.9], 0.6 [0.3–1.4], 0.7 [0.3–1.6], 0.4 [0.2–0.8], 0.4 [0.2–0.8], and 0.3 [0.1–0.7], respectively. Adjusted OR was 1.22 [1.10–1.34] for younger age by decade, 1.41 [1.11–1.79] for male, 2.69 [1.52–4.76] for use of oral CS (&gt; 0 and &lt; 5 mg/day of prednisolone [PSL] equivalent dose versus no use), 2.21 [1.26–3.86] for oral CS (≥ 5 and &lt; 10mg/day versus no use), and 1.25 [1.02–1.54] for dyslipidemia. Conclusion: Significant decrease in IR of ON after 2015 was observed in Japanese patients with SLE for the first time. Younger age, use of CS, and dyslipidemia were identified as significant risk factors of ON. References: [1]Rheumatology 2018;57(5):844-9. [2]BMJ Open. 2017;7(7):e016788. [3]Eur J Intern Med. 2016;35:e23-e4. Disclosure of Interests: Ryoko Sakai Speakers bureau: RS received fees from Bristol Myers Squibb Co., Ltd., Grant/research support from: Tokyo Women’s Medical University (TWMU), particularly the Division of Multidisciplinary Management of Rheumatic Diseases, Department of Rheumatology, has received unrestricted research grants from Ayumi Pharmaceutical Co.; Chugai Pharmaceutical Co., Ltd.; Eisai Co., Ltd., Nippon Kayaku Co., Ltd.; Taisho Toyama Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma Co.; and Teijin Pharma Ltd., with which TWMU paid the salaries of RS., Eiichi Tanaka Speakers bureau: ET has received lecture fees from Abbvie, Asahi Kasei pharma co., Astellas Pharmaceutical, Ayumi Pharmaceutical, Chugai Pharmaceutical, Eisai Pharmaceutical, Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kyowa Pharma Chemical CO.,LTD., Janssen Pharmaceutical K.K., Mochida Pharmaceutical CO.,LTD., Pfizer, Takeda Pharmaceutical, and Teijin Pharma Ltd., Consultant of: ET has received lecture fees from Abbvie, Asahi Kasei pharma co., Astellas Pharmaceutical, Ayumi Pharmaceutical, Chugai Pharmaceutical, Eisai Pharmaceutical, Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kyowa Pharma Chemical CO.,LTD., Janssen Pharmaceutical K.K., Mochida Pharmaceutical CO.,LTD., Pfizer, Takeda Pharmaceutical, and Teijin Pharma Ltd., Miku Yamagishi: None declared, masako majima: None declared, masayoshi harigai Speakers bureau: MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co.,Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant of: MH is a consultant for AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co., Ltd. and Teijin Pharma., Grant/research support from: MH has received research grants from AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc., Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekisui Medical, Shionogi &amp; Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd.