Abstract Number: PB1165
Meeting: ISTH 2020 Congress
Background: Emicizumab, a humanized bispecific antibody that activates factor X without factor VIII, has improved convenience for hemophilia A prophylaxis and decreased bleeding. Elevated osteoclastic activity and depressed osteoblastic activity have been reported in persons with hemophilia A (PwHA). The relationship of emicizumab to bone biomarkers has not been explored.
Aims: To measure the osteoclastic biomarker carboxy terminal telopeptide of collagen type 1 (CTX1) and osteoblastic osteoprotegrin (OPG) in PwHA on emicizumab in comparison to baseline results prior to emicizumab, and to controls.
Methods: Biobank samples from a consented single-center cohort study (HemoPICS) of PwHA on emicizumab were assayed by ELISA for CTX1 and OPG (R&D Systems). Comparisons of pre and post emicizumab values to age-matched controls were analyzed using independent samples t-tests. Intra-group relationships were evaluated using Pearson’s correlations. Pre-emicizumab samples were from time of FVIII trough.
Results: Normal reference ranges for CTX1 and OPG were derived from 30 healthy adults and 32 children. In controls, both CTX1 and OPG were significantly lower in adults than children (p< 0.001), and OPG correlated negatively with age (r=-0.38, p=0.003). Figure 1 shows CTX1 and OPG levels in 33 PwHA prior to and on emicizumab in comparison to controls. In adults, CTX1, previously reported to be elevated in adult PwHA, was higher than controls both before and on emicizumab. In pediatric PwHA, CTX1 did not differ from controls before or on emicizumab, but OPG was lower (p=0.01). In PwHA, OPG trended towards increasing with age regardless of treatment (r=0.32, p=0.07).
Conclusions: Adult PwHA showed elevated osteoclastic CTX1 both before and on emicizumab compared to controls. OPG decreased significantly with age in controls, but seemed to increase with age in PwHA. The clinical significance of these findings is unknown and requires longer observation in a larger cohort of PwHA on prophylaxis with FVIII or emicizumab.
To cite this abstract in AMA style:Warren B, Taylor J, Branchford B, Ng C, Ambruso D, Briones N, Tran A, Jacobson L, Thornhill D, Moyer G, Norton K, Buckner TW, Wang M, Manco-Johnson MJ. Emicizumab beyond Annualized Bleeding Rate: How Does Emicizumab Affect Bone Biomarkers? [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/emicizumab-beyond-annualized-bleeding-rate-how-does-emicizumab-affect-bone-biomarkers/. Accessed January 21, 2022.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/emicizumab-beyond-annualized-bleeding-rate-how-does-emicizumab-affect-bone-biomarkers/