THU0514 Effect of Long-Term Treatment with Anakinra (Kineret®) on Bone Mineral Density in Patients with Severe Cryopyrin-Associated Periodic Syndromes
Authors: K. Timdahl, R. Goldbach-Mansky, M. Leinonen, H. Olivecrona
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Cryopyrin-Associated Periodic Syndromes (CAPS) include a group of rare inherited autoinflammatory diseases consisting of Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome and the most severe form, Neonatal Onset Multisystem Inflammatory Disease (NOMID). Anakinra is an IL-1-receptor antagonist that has proven effective and safe in the treatment of severe CAPS<sup>1</sup> with reported sustainable reduction of chronic inflammation, organ specific inflammation, steroid use and a growth catch-up after long-term use<sup>2</sup>. The beneficial effect of anakinra on bone mineral density (BMD) has been reported in a small cohort of patients with rheumatoid arthritis<sup>3</sup> but BMD data in patients with severe CAPS have not yet been investigated. <h3>Objectives</h3> To evaluate the changes in BMD in patients with severe CAPS during anakinra treatment up to 60 months. <h3>Methods</h3> A prospective, open-label, single arm study of anakinra including 43 patients was conducted at the National Institutes of Health<sup>1</sup>. The study included yearly assessment of BMD using dual energy X-ray absorptiometry (DEXA) scans (g/cm<sup>2</sup>) with a Hologic Densitometer. The BMD was assessed at the total hip, intertrochanteric, femoral neck and L1-L4 (anterior posterior) and evaluated using age-, gender-, and race-matched Z-scores based on DEXA assessments (normal Z-score: -2 to +2) at baseline and up to 60 months. The changes from baseline were estimated in the intention-to-treat population using a mixed model for repeated measures (MMRM) and the proportions of patients with abnormally low values (&lt;-2) tabulated for observed cases. <h3>Results</h3> Baseline and follow-up BMD data were obtained from 24 out of the 43 patients (16 patients lacked baseline data, 2 lacked post-baseline data and 1 had no BMD data). At baseline, the mean (SD) Z-scores were -2.22 (0.51), -1.96 (1.39), -1.92 (1.92) and -1.75 (1.84) at the femoral neck, L1-L4, total hipand intertrochanteric, respectively. The proportion of abnormally low BMD values in the 4 areas at baseline was 49.4%. There was an increase in the mean BMD values observed throughout the study. The mean (SD) Z-scores at Month 60 were -1.08 (1.63), -0.74 (1.47), -0.80 (1.60) and -0.96 (1.63) at the femoral neck, L1-L4, total hip and intertrochanteric, respectively; the change from baseline was significant (p&lt;0.001) for all locations. Largest increases were seen during the first 36 months. Altogether 54.1% of the BMD values abnormally low at baseline normalized during the study, while 8.8% of the normal values changed to abnormal. <h3>Conclusions</h3> Approximately half of the baseline BMD values were subnormal. After 60 months of anakinra treatment approximately half of these values normalized and the mean Z-scores increased from around -2 at baseline to around -1, indicating an acquisition of BMD exceeding that of normal growth. These data are in agreement with previous reports on growth catch-up, reduced inflammation and decreased steroid use in these patients. <h3>References</h3> Goldbach-Mansky et al. NEJM. 2006;355:581-92. Sibley et al. Arthritis Rheum. 2012;64:2375-86. Athanassiou et al. Bone 2009;44 Suppl 2:S387-S388. <h3>Disclosure of Interest</h3> K. Timdahl Shareholder of: Sobi, Employee of: Sobi, R. Goldbach-Mansky Grant/research support from: Sobi, Regeneron and Novartis, M. Leinonen Consultant for: Sobi, H. Olivecrona Employee of: Sobi