FRI0480 CHANGES IN CIRCULATING SCTLA-4 FOLLOWING ZOLEDRONIC ACID INFUSION
Authors: Gerolamo Bianchi, Daniele Saverino, Dario Camellino, Andrea Giusti, Erika Iervasi, Giuseppe Girasole, Socrates Papapoulos
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Acute phase response (APR) is a transient, flu-like reaction to first exposure to intravenous nitrogen-containing bisphosphonate (NBP). APR is characterised by a strong inflammatory response, associated with increases in circulating levels of IL-6 and TNF-, that is thought to be due to activation and increased proliferation of γδ T cells related to the molecular mechanism of action of NBP. Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4), in both its soluble (s) and membrane-bound forms, is involved in the downregulation of T cell proliferation, cell cycle progression and cytokine production. High levels of serum sCTLA-4 have been reported in several autoimmune diseases, and its role as both inhibitor and enhancer of the immune response has been proposed. <h3>Objectives</h3> To evaluate the potential relationship between sCTLA-4 and the development of APR in patients treated with zoledronic acid (ZOL). <h3>Methods</h3> Included in the study were patients treated with a single intravenous ZOL infusion 5 mg. Exclusion criteria were previous treatment with ZOL, treatments interfering with CTLA-4, and estimated glomerular filtration rate &lt;35 ml/min. APR was defined as a rise in axillary temperature above 38°C at any time during the first 48 hours and an increase in musculoskeletal pain by more than 10 mm in a visual analogue scale (VAS, from 0 to 100 mm). Clinical and laboratory parameters were assessed at baseline, before ZOL, and at 24, 48 and 72 hours after the infusion. <h3>Results</h3> Ten female patients (mean age 73-10 years) were included (2 had vertebral fractures and the remaining had osteoporosis), 5 of whom experienced APR (APR+) associated with the expected increases in serum CRP and IL-6. Baseline levels of sCTLA-4 did not differ between APR+ and APR- patients and decreased significantly in all from 32-9 ng/ml to 24-9 ng/ml (p=0.007) at 24 hr, 16-8 ng/ml (p=0.004) at 48 hr and 7-6 ng/ml (p&lt;0.001) at 72 hr. Absolute value of sCTLA-4 and mean% change of sCTLA-4 after ZOL were not statistically different between APR+ and APR- patients. At 72 hr, sCTLA-4 decreased by 77% (-23%) in APR+ and by 81% (-20%) in APR- (p=0.786). There were no statistically significant correlations between serum sCTLA-4 levels with any clinical or biochemical parameter of APR. <h3>Conclusion</h3> Contrary to our hypothesis, sCTLA-4 was not related to the occurrence of APR after ZOL. The significance of the substantial decrease of circulating levels of sCTLA-4 after ZOL in all studied patients warrants further investigation. <h3>Disclosure of Interests</h3> Gerolamo Bianchi Consultant for: Alfa-Sigma, Amgen, BMS, Celgene, Medac, UCB, Speakers bureau: Abbvie, Abiogen, Alfa-Sigma, Amgen, BMS, Celgene, Daniele Saverino: None declared, Dario Camellino Consultant for: Janssen-Cilag, Novartis, AbbVie, Sanofi, Paid instructor for: Mylan, Andrea Giusti Grant/research support from: Abiogen Pharma, Consultant for: EffRx, Speakers bureau: Abiogen Pharma, Eli Lilly, AMGEN, Erika Iervasi: None declared, Giuseppe Girasole: None declared, Socrates Papapoulos Grant/research support from: No in the last 3 years, Consultant for: Amgen, Axsome, Gador, Radius Health, UCB, Speakers bureau: Amgen, UCB