OBJECTIVES: The primary treatment for minor to moderate bleeding disorders in haemophilia patients with inhibitors is either rFVIIa or aPCC. The efficacy of both products has been evaluated in individual studies; however there has not been an overall review and attempt to establish a valid estimate of the effectiveness of rFVIIa and aPCC. We undertook a systematic review of the literature in an attempt to establish robust estimates of the efficacy, speed of bleed resolution, and adverse event profile of both rFVIIa and aPCC.
METHODS: We identified 11 open-label cohort studies, six randomized clinical trials, including two head-to-head clinical trials and a meta-analysis. The definition of efficacy varies between these studies, but is usually a composite measure of definite relief of pain, reduction in the size of the haemorrhage, and cessation of bleeding. The individual making the interpretation of efficacy (i.e., the clinician, the patient/caregiver, or a combination of both) and the time from treatment initiation to the recording of the efficacy endpoint also varies across the studies.
RESULTS: Overall, estimates of efficacy based on randomized clinical trials using dosing regimens in line with guidelines are higher for rFVIIa (81%-91%) than for aPCC (64-80%). Conclusions from a meta-analysis suggest that treatment with rFVIIa may be associated with a faster time to joint bleed resolution than aPCC due to higher efficacy levels at 12, 24 and 36 hour time points. The results from a comparative trial support the improved efficacy rates associated with rFVIIa compared to aPCC.
CONCLUSIONS: In general, the studies do report higher efficacy and bleed cessation rates for rFVIIa than for aPCC; however, the measurement of effectiveness of the agents is open to interpretation due to variety of methods being used to evaluate effectiveness. Further head-to-head trials should incorporate a standardized measurement for defining efficacy.
