Human Plasminogen Replacement Therapy Vs. Best Supportive Care in Patients with Congenital Plasminogen Deficiency: A Comparison of Health Care Resource Use over a 48-Week Period

Background: Congenital plasminogen deficiency (CPD), is an ultra-rare autosomal recessive disorder that causes severe and debilitating clinical sequelae. Clinical signs are characterized by ligneous conjunctivitis, gingivitis, otitis media, impaired wound healing and even hydrocephalus. Current disease management includes surgery and systemic/topical therapies, but successful clinical responses are few and recurrences are typically rapid. Intravenous (IV) human plasminogen is a new treatment for CPD currently undergoing regulatory review in the United States. A recent clinical trial demonstrated that regular infusions of plasminogen IV (every 2 to 4 days) induced near complete and long term durable responses in affected patients. The current study compared overall health care resource use required to manage clinical manifestations of CPD for patients treated with human plasminogen in the clinical trial relative to a historical control group.

Methods: The registration trial database was used to extract health care resource data in CPD patients (n=14) who received human plasminogen IV therapy throughout a 48-week period. Total health care resource use was compared to a control sample consisting of CPD patients (n=16) who did not receive human plasminogen IV and were managed with only best supportive care (BSC) over a one year period from the date of diagnosis. Health care resource extraction consisted of topical and systemic therapies such as fresh frozen plasma (FFP), clinic visits, surgical interventions and hospital admissions related to CPD.

Results: A total of 16 patients who received BSC in either the United States (n=3), Spain (n=3) and Turkey (n=10) were identified and formed the control group. Over a 12-month assessment period, there were 304 clinic visits and 65 days of hospitalization for CPD related complications. IV FFP was given to 12 of 16 (75%) patients, which translated to 246 individual FFP doses administered (dose range = 5 to 15 mg/kg) over 12 months. Furthermore, there were 54 eye surgeries performed on the 16 control patients to remove ligneous membranes. In contrast, none of the 14 patients treated with plasminogen IV required surgical interventions, hospital admissions or FFP infusions over the 48-week treatment period (p < 0.001). There were also significant reductions in all types of supportive therapy in the human plasminogen treated patients relative to their utilization at baseline (p < 0.05).

Conclusions: Human plasminogen replacement therapy was able to significantly offset health care resource use compared to patients receiving BSC only. Patients in the trial were also able to incorporate IV human plasminogen therapy into their weekly routine, with administrations often performed at home.