Background 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 CAPS1 with reported sustainable reduction of chronic inflammation, organ specific inflammation, steroid use and a growth catch-up after long-term use2. The beneficial effect of anakinra on bone mineral density (BMD) has been reported in a small cohort of patients with rheumatoid arthritis3 but BMD data in patients with severe CAPS have not yet been investigated.
Objectives To evaluate the changes in BMD in patients with severe CAPS during anakinra treatment up to 60 months.
Methods A prospective, open-label, single arm study of anakinra including 43 patients was conducted at the National Institutes of Health1. 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 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 (<-2) tabulated for observed cases.
Results 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<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.
Conclusions 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.
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Sibley et al. Arthritis Rheum. 2012;64:2375-86.
Athanassiou et al. Bone 2009;44 Suppl 2:S387-S388.
Disclosure of Interest 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