The importance of biomarkers of joint damage in monitoring the efficacy of different prophylaxis regimens for severe haemophilia A

Abstract

Background: Haemophilic arthropathy, with characteristic joint dam- age, is the main cause of morbidity in individuals with severe haemo- philia A. The most important clinical strategy for management of these patients is treatment by continous prophylaxis with intrave- nously applied factor (F) VIII. Recently, it was shown that serum and/ or urine biomarkers of cartilage turnover in joints reflected the degree of total joint degradation in haemophilia patients. Aims: The aims of this study were to detect correlations between serum and urine concentrations of biomarkers of joint cartilage degradation and the radiological score for haemophilic arthropathy, as well as to estimate whether measurement of these biomarkers could be useful in monitoring the efficacy of different (secondary) prophylaxis regimens for severe haemophilia A. Methods: This single-center study included 20 adult males with severe haemophilia A manifested by plasma FVIII < 1% of normal, without inhibitor. The first group involved five patients treated with full-dose prophylaxis: 20 U/kg three times per week. The second group included five patients given intermediate-dose prophylaxis: 10–15 U/kg three times per week. The third group consisted of 10 patients treated on demand (i.e. only in acute bleeding episodes). The following joint carti- lage degradation products were measured: serum cartilage oligomeric matrix protein (COMP) and urinary C-terminal telopeptide of type II collagen (CTX-II). Blood and urine samples were collected initially, before the start of treatment (marked as COMP-1 and CTX-II-1) and after 3 months follow-up (marked as COMP-2 and CTX-II-2). Radio- logical evaluation of haemophilic arthropathy was estimated initially according to the Pettersson score. Approval from the local Ethics Committee and informed written consent were obtained from each subject. Results: The mean age of the patients was 32 years (range 19–55). The results showed significant positive correlations between the number of points in the Pettersson score and both COMP level (r = 0.602, P = 0.006) and CTX-II level (r = 0.580, P = 0.009). In the group of patients given full-dose prophylaxis, the mean value for COMP-2 was significantly lower than that for COMP-1 (P = 0.043), while in the group of patients receiving intermediate-dose prophylaxis and in those treated on demand the mean values of COMP-2 were not significantly changed when compared to those for COMP-1. Likewise, in the group of patients treated with full-dose prophylaxis, the mean value for CTX-II-2 was significantly lower than that for CTX-II-1 (P = 0.014). Moreover, the mean value of CTX-II-2 was also significantly decreased compared to that for CTX-II-1 (P = 0.028) in the group receiving intermediate-dose prophylaxis. The mean values of CTX-II in the group of patients treated on demand showed no change. Conclusions: Joint cartilage degradation products, such as the biomar- kers: serum COMP and urinary CTX-II, can provide an estimation of the amount of joint damage in patients with haemophilia A. Measure- ment of serum/urinary biomarker levels is useful for monitoring the efficacy of the applied doses of FVIII in different treatment approaches towards these patients.