AB0997 Clinical characteristics of non-responder to denosumab treatment for postmenopausal osteoporosis in japanese woman
Authors: I. Yoshii
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Denosumab (d-mab), an anti-receptor activator of nuclear factor kappa-B ligand (RANKL) monoclonal antibody, is now widely used in postmenopausal osteoporosis (OP) treatment. It can attain reliable increase of bone mineral density (BMD) despite any OP drugs previous used, and that can be predicted in a long period. However, sometimes we observe BMP decrease. Factor that suppresses BMD gain is still unclear. <h3>Objectives</h3> This study investigates non-responder to d-mab, and attempted to evaluate factors that concerns non-responder in clinical practice retrospectively. <h3>Methods</h3> 212 postmenopausal OP patients have been treated with d-mab continuously for more than two years under vitamin D supplement and calcium since June 2013. These patients were enrolled, and their clinical background (CBs) such as age at start of d-mab, past history of bone fragility fracture, alcohol habitat, current smoking, being treated for rheumatoid arthritis (RA), glucocorticoid steroid thrown, OP drug naïve, length of administration (LA), concurrence of lifestyle disease (LSD) such as diabetes mellitus, hypertension, and chronic obstructive lung disease, and number of comorbidity (N.Com), were investigated (table 1a). BMD of lumbar spine (LS), femoral neck (FN), greater trochanter (GT), and whole femur (WF) at the start and every six months thereafter were measured. Tartrate-resistant Acid Phosphatase 5b (TRACP5b) and total dose of type-one pro-collagen -N- pro-peptide (P1NP) at the same time of BMD measurement, and reduction ratio (RR) of them compared to the first shot were calculated. Patients were divided into two groups whether BMD increased. BMD in each part at final measurement relative to that at start was compared statistically with paired T-test. CBs were statistically evaluated between the two BMD groups (Res and n-Res; Responder and non-Responder) with Mann-Whitney U-test (MWT), and then correlation between the BMD groups and factors of CB that had demonstrated significantly difference, and TRACP5b and P1NP was also evaluated statistically with Binary Logistic Analysis (BLR). Statistical significance was set less than 5%. <h3>Results</h3> For all patients, BMD in LS, WF, and GT demonstrated significant increase at final measurement than at start (p&lt;0.001), while FN demonstrated no significant increase. However, n-Res counted 30, 89, 46, and 44 for LS, FN, WF, and GT, respectively. LA demonstrated negative significant correlation for being n-Res in all part, while LSD, N.Com, TRACP5b at start, and RR of TRACP5b at second shot and last shot, demonstrated significant positive correlation in LS with MWT. However, with BLR, only RR of TRACP5b at second shot demonstrated significant negative correlation with n-Res in LS (OR:0.0702, 95% CI:0.0051–0.9655) with 0.39 cut-off index (COI), while no other factors but LA demonstrated significant negative correlation with n-Res in WF (OR:0.9669, 95% CI:0.9433–0.9911) and GT (OR:0.9632, 95% CI:0.9391–0.9878) with 26 and 24 months COI, respectively (table 1b). Table 1a Patient's background. Age at Start, Length Administered, Number of Chronic Comorbidities, and Bone Mineral Density, show average value and standard deviation. The other parameters show numbers.%YAM:% of young adult mean value. LS: lumbar spine, FN: femoral neck, WF: whole femur, GT: greater trochanter, SERM: selective oestrogen receptor modulator. Table 1b Parameters that demonstrated significant difference between responder and non-responder to denosumab, and their p-values, and results of these parameters with binary logistic regression analysis. LS: lumbar spine, FN: femoral neck, WF: whole femur, GT: greater trochanter, LSD: concurrence of lifestyle disease, LA: length of administration, N.Com: number of concurrent comorbidities, TRACP5b at start; tartrate-resistant acid phosphatase 5b (TRACP5b) at start of administration, rTRACP5b@1stP: reduction ratio of TRACP5b of second shot compared to the first, rTRACP5b@LT: reduction ratio to TRACP5b of last shot compared to the first, Drug Naive: initial drug as osteoporosis treatment, PINP: total dose of type-one pro-collagen –N- pro-peptide. <h3>Conclusions</h3> These results suggest that non-responder to d-mab exists. Length of administration works for BMD to increase in femur, and concurrence of LSD, and N.Com are suggested to be risk factors in LS. Less reduction ratio of TRACP-5b at second shot is referred for prediction of non-responder. However, there is no parameter that predicts non-responder before administration. <h3>Disclosure of Interest</h3> None declared