Objective:
Joint status was assessed in the 3-year SPINART study, which compared routine prophylaxis versus on-demand treatment in adults with severe hemophilia A. We report joint outcomes at year 3 obtained using magnetic resonance imaging (MRI).
Methods:
The open-label, randomized, controlled, parallel-group, multinational SPINART study enrolled males aged 12–50 years with severe hemophilia A who had ≥150 exposure days with any factor VIII (FVIII) product, no inhibitors, no prophylaxis for >12 consecutive months in the past 5 years, and 6–24 documented bleeding events or treatments in the previous 6 months. Patients were treated with Bayer’s sucrose-formulated recombinant FVIII (rFVIII-FS), either on demand or as prophylaxis (25 IU/kg 3 times weekly, with dose escalation by 5 IU/kg permitted once per year). MRI was performed at baseline and year 3 to evaluate the structure of 6 index joints. Each MRI was read by 3 radiologists blinded to treatment assignment who independently completed the extended MRI (eMRI) scale; higher eMRI scores indicate greater joint structure damage. The score for each joint was based on the readers’ median change score for each of the 45 eMRI scale items when comparing MRIs from different timepoints. Total patient score was derived; change from baseline in total patient score was prespecified as the first in a hierarchy of 2 secondary endpoints. Between- group comparison was made using constrained longitudinal data analysis. Data are presented for the intent-to-treat population.
Summary:
Of 84 patients enrolled (42 per treatment group), MRI data were available for 38 on-demand and 41 prophylaxis patients. Least squares (LS) mean change from baseline to year 3 on the eMRI scale total score was 0.96 for on demand and 0.79 for prophylaxis (LS mean difference, –0.17; 95% CI, –0.92 to 0.59; P=0.66). LS mean change from baseline to year 3 for on demand and prophylaxis was 0.06 and 0.01 for the eMRI soft-tissue domain (LS mean difference, –0.04; 95% CI, –0.18 to 0.10; P=0.53) and 0.90 and 0.78 for the eMRI osteochondral domain (LS mean difference, –0.12; 95% CI, –0.82 to 0.58; P=0.74).
Conclusions:
In adults with severe hemophilia A, progression of structural joint damage was not significantly different between patients using rFVIII prophylactically or on demand over a 3-year follow-up period, although less progression was seen with prophylaxis.