Meta-analytic review of the clinical effectiveness of oral deferiprone (L-1)

Objective: To summarize efficacy and effectiveness in iron overloaded patie nts treated with the orally active iron chelator deferiprone also known as Lx or, using meta-analysis of the literature. Methods: We reviewed the literature, searching Medline and Embase databases , as well as reviews and other literature on the topic. Inclusion criteria were: original clinical trials reporting results for serum ferritin concent ration (SF), hepatic iron concentration or urinary iron excretion (UIE). Ef ficacy data had to have been reported after greater than or equal to 3 mont hs of treatment. Data were combined using a random effects model (Cochrane) modified for use with single groups to produce a point estimate and a 95% confidence interval. To summarize the clinical effectiveness, overall propo rtion of patients where deferiprone was able to reduce serum ferritin was c alculated. We also examined average (mg.1(-1)) serum ferritin levels over t he reported time (mean) and absolute decrease from the baseline after thera py. To summarize efficacy, success was defined as the proportion of patient s who achieved UIE of 25 mg per day or 0.5 mg.kg(-1) day(-1), which equals the average amount received from monthly blood transfusions. We also calcul ated the overall average level (mg per day) of UIE over the reported time o f therapy (mean). As part of a sensitivity analysis, data were analyzed for two ranges of deferiprone dosage: less than or equal to 50 mg.kg(-1).day(- 1) and greater than or equal to 75 mg.kg(-1).day(-1). Results: Of 83 identified references, nine clinical trials met our inclusio n criteria, providing data for 129 iron overloaded patients. After a mean o f 16 months of therapy (range 6.4-36 months) with 66.4 mg.kg(-1) day(-1) (m ean) of deferiprone, 75.5% of highly iron overloaded patients had a decreas e in serum ferritin from baseline. The average drop in serum ferritin of 0. 8 mg.1(-1) was 23.5% from baseline. The overall average UIE for therapy was 28.8 mg per day in patients receiving greater than or equal to 75 mg.kg da y(-1) over 8.5 months of therapy. At the same dosage, more than half of the patients (51.8%) achieved negative iron balance. When studies with patient s receiving lower dosage (less than or equal to 50 mg.kg(-1) day(-1)) were included, the success rate was 45.1%. Conclusion: Overall, deferiprone has clinical efficacy in achieving negativ e iron balance and reducing body iron burden in highly iron overloaded pati ents. After an average of 16 months of deferiprone in doses greater than or equal to 75 mg kg(-1)day(-1), most patients had a decrease in ferritine co ncentration.