POS0532\u2005AveRAGE PREDNISOLONE DOSE OF ONLY 1 MG PER DAY WAS RISK FACTOR FOR CLINICAL FRACTURES IN PATIENTS WITH RHEUMATOID ARTHRITIS - NINE-YEAR FINDINGS OF THE TOMORROW STUDY

Abstract

Previous cohort studies showed that the use of prednisolone (PSL) was a risk factor for clinical fractures in patients with rheumatoid arthritis (RA). However, there are few reports on relationship between PSL dose and clinical fractures.The present study aimed to determine the effect of PSL dose on the incidence of clinical fractures in the RA patients treated with PSL.We evaluated anthropoetric parameters, bone mineral density (BMD), disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), RA medication (methotrexate (MTX) dose, use of biologic disease modified anti-rheumatic-drugs (bDMARDs), and PSL dose) and the incidence of clinical fractures during nine years in RA patients who participant the TOMORROW study (UMIN000003876), which is a 10-years prospective cohort study. Data on clinical fracture was self-reported on the questionnaires. In this analysis, the data of RA patients treated with PSL at least once during nine-year period were evaluated. We analyzed the average dose of PSL until the incidence of the clinical fractures. The risk factor for clinical fractures were analyzed by using Cox proportional hazard model with adjustment for age, sex, body mass index (BMI), and smoking history.We analyzed the data of 67 RA patients treated with PSL. Among them, median age was 61.8 year, 56 patients (83.6%) were female, 47 patients (70.1%) were never smoker and median disease duration was 12.1 year. The number of patients treated with PSL at baseline was 48 (69.1%). During 9 years, 23 clinical fractures were observed in 67 patients, and the incidence of clinical fracture was 0.046/person-year. In 19 patients, who were not treated with PSL at baseline but treated with PSL at least once during 9 years, 5 clinical fractures were observed. In 67 RA patients, Cox proportional hazard analysis revealed that baseline disease activities, BMD at thoracic vertebrae and medication were not significant risk factors for clinical fractures. However, average PSL dose of more than only 1\u2009mg/day was a significant risk factor for the incidence of clinical fracture (hazard ratio (HR): 2.80; p=0.03) (Table 1).Table 1.Adjusted hazard ratio for clinical fractures in patients with rheumatoid arthritis treated with PSL.* Adjusted Hazard ratio95% Confidence intervalP valueCRP (mg/dL)1.290.88-1.910.19RF (IU/mL)0.990.99-1.000.07ACPA (U/mL)0.990.98-1.000.18DAS28-ESR0.990.71-1.390.97BMD at thoracic vertebrae (mg/cm2)0.020.00-1.000.05bDMARDs use0.550.23-1.320.18Bisphosphonate use2.330.95-5.710.07average dose of MTX (mg/week)1.020.92-1.120.74average score of DAS28-ESR1.150.76-1.750.52average dose of PSL more than 1mg/day2.81.09-7.240.03*Hazard ratio was adjusted for age, sex, body mass index (BMI), and smoking history. RF, Rheumatoid factor; ACPA, Anti-cyclic citrullinated peptide antibody; DAS28-ESR, disease activity score 28-erythrocyte sedimentation rate; BMD, Bone mineral density; bDMARDs, biologic disease modified anti-rheumatic-drugs; MTX, methotrexate; PSL, prednisolone.In RA patients treated with PSL, average PSL dose of only 1mg/day significantly increased the risk for the incidence of clinical fractures. Even for established RA patients, continuous use or initiation of low PSL dose was apparently significant risk factor for clinical fractures.Hitoshi Yoshimura: None declared, Tatsuya Koike Grant/research support from: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, Kenji Mamoto: None declared, Yuko Sugioka: None declared, Tadashi Okano: None declared, Masahiro Tada: None declared, Kentaro Inui Grant/research support from: Janssen Pharmaceutical K.K. and Astellas Pharma Inc, Hiroaki Nakamura: None declared