Results Introduction Conclusion Methods THU0514 References EFFECT OF LONG-TERM TREATMENT WITH ANAKINRA (KINERET®) ON BONE MINERAL DENSITY IN PATIENTS WITH SEVERE CRYOPYRIN-ASSOCIATED PERIODIC SYNDROMES K. Timdahl1, R. Goldbach-Mansky2, M. Leinonen1,3, and H. Olivecrona1 1Swedish Orphan Biovitrum, Stockholm, Sweden, 2National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United States, 34Pharma AB, Stockholm, Sweden THU0514 Results Baseline and follow-up BMD data were obtained from 24 (20 pediatrics; 4 adults) out of the 43 patients (16 patients lacked baseline data, 2 lacked post-baseline data and 1 had no BMD data). Baseline analysis At baseline, the mean (SD) Z-scores were -1.96 (1.39), -2.22 (0.51), -1.75 (1.84), and -1.92 (1.92), at the L1-L4, femoral neck, intertrochanteric, and total hip, respectively. (Figure 1) The proportions of patients with abnormally low BMD values were 47.8%, 55.0%, 50.0%, and 45.0% at the L1-L4, femoral neck, intertrochanteric, and total hip, respectively. The total proportion of abnormally low BMD values was 49.4% in the 4 locations. (Figure 2) BMD analysis An increase in the mean BMD values was observed throughout the study. The mean (SD) Z-scores at 60 month were -0.74 (1.47), -1.08 (1.63), -0.96 (1.63), and -0.80 (1.60), at the L1-L4, femoral neck, intertrochanteric, and total hip, respectively. Largest increases were seen during the first 36 months. (Figure 1) In the MMRM analysis of combined Z-score data of all 4 locations, evaluating changes from baseline to Month 12, 24, 36, 48 and 60, steroid use (p=0.191) or location (p=0.644) did not have a significant effect, while the improvement in Z-scores was significant (p<0.001). The total proportion of the abnormally low Z-scores decreased from 49.4% (baseline) to 23.2% (month 60) in the 4 locations. The proportions of patients with abnormally low BMD values over time by location are shown in Figure 2. Altogether, 54.1% of the abnormally low Z-scores at baseline normalized during the study, while 8.8% of the normal values changed to abnormally low. Figure 2. Decreased percentage of patients with abnormally low Z-score upon anakinra treatment Introduction Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of IL-1-driven rare inherited autoinflammatory diseases of varying severity1-4: - Familial Cold Autoinflammatory Syndrome (FCAS; mild) - Muckle-Wells Syndrome (MWS; moderate) - Neonatal-Onset Multisystem Inflammatory Disease (NOMID; severe) Anakinra is an IL-1-receptor antagonist that blocks the biologic activity of naturally occurring IL-1 and has proven effective and safe in the treatment of severe CAPS5 with reported sustainable reduction of chronic inflammation, organ specific inflammation, steroid use and a growth catch-up after long-term use6. Anakinra is approved for the treatment of NOMID in the US and in the EU for the treatment of all types of CAPS. The beneficial effect of anakinra on bone mineral density (BMD) has been reported in a small cohort of patients with rheumatoid arthritis7, but BMD data in patients with severe CAPS has to our knowledge not yet been investigated. The objective of the present analysis is to evaluate the changes in BMD in patients with severe CAPS during anakinra treatment up to 60 months in an analysis of previously reported data. Conclusion At baseline, approximately half of the BMD values were abnormally low. After 60 months of anakinra treatment, the mean Z-score increased from around -2 at baseline to around -1, and approximately half of the abnormally low BMD values normalized. This indicates an acquisition of BMD exceeding that of normal growth. An improvement in proportion of abnormally low Z-scores was seen upon anakinra treatment in non-steroid users as well as steroid users. The present data are in agreement with previous reports on growth catch-up, reduced inflammation and decreased steroid use in these patients. Figure 1. Increased bone mineral density upon anakinra treatment Steroid analysis At baseline, 14 out of 24 patients received steroids. During the study, these patients either stopped or decreased their steroid dose. A correlation between the abnormally low Z-scores and steroid use was seen. At baseline, the proportion of patients with abnormally low Z-scores was higher among the steroid users as compared to non-steroid users (65.4% vs. 25.9%). Anakinra therapy resulted in an improvement from baseline in abnormally low Z-scores in both non-steroid users and steroid users. (Figure 3) Figure 3. Improvement in abnormally low Z-scores upon anakinra treatment in non-steroid users as well as steroid users (four locations combined) Methods This analysis is based on data from a prospective, open-label, single arm study of anakinra including 43 patients that was conducted at the National Institutes of Health5. The study included yearly assessment of BMD using dual energy X-ray absorptiometry (DEXA) scans (g/cm2) with a Hologic Densitometer. The BMD was assessed at the L1-L4 (anterior posterior), femoral neck, intertrochanteric, and total hip, 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 mean changes from baseline (i.e. initiation of anakinra treatment) to 60 months, with regards to Z-scores, were estimated in the intention-to-treat population using a mixed model for repeated measures (MMRM) and the proportions of patients with abnormally low Z-score (<-2) were tabulated for observed cases. References Feldmann, et al. Am J Hum Genet. 2002;71:198-203. Aksentijevich, et al. Arthritis Rheum. 2002;46:3340-3348. Hoffman, et al. Nat Genet. 2001;29:301-305. Goldbach-Mansky et al, Curr Rheumatol Rep. 2011;13:123-131. 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.   Authors disclosures: The study was sponsored and conducted by the NIH. Swedish Orphan Biovitrum (Sobi) has performed the analyses included in this work in collaboration with the NIH. Kristina Timdahl is a shareholder and employee of Sobi. Raphaela Goldbach-Mansky has received grant/research support from Sobi, Regeneron and Novartis. Mika Leinonen is a consultant for Sobi. Hans Olivecrona is an employee of Sobi.