The Satety and effectiveness of Deferiprone in a large-scale, 3-year study in Italian patients

Authors
Adriana Ceci, Paola Balardi, Mariagrazia Felisi, Maria Domenica Cappelleni, Vittorio Carnelli, Vincenzo De Sanctis, Renzo Galanello, Aurelio Maggio, Giuseppe Masera, Antonio Piga, Francesco Schettini, Ippazio Stefano, and Fernando Tricta

Journal
British Journal of Haematology, 2002, Vol. 118 pp 330-336

Background
In 1997, the Italian Ministry of Health included deferiprone in the list of drugs to be used under controlled conditions, permitting the use of the drug before Marketing Authorization was issued by the EMEA. This also allowed for the accumulation of increased information regarding the safety and effectiveness of deferiprone without denying access to patients who needed an alternative therapy. The Italian Registry for Controlled Use of Deferiprone was established and was able to provide evidence about safety and efficacy of deferiprone in clinical practice settings. This study looks at 3 years of clinical experience with the use of deferiprone.

Methodology

• Large-scale, prospective, safety and efficacy study involving 532 patients from 86 thalassaemia centers.
• Inclusion criteria for the program included: (1) serious toxicity with DFO therapy, (2) diagnosis of thalassaemia with iron overload documented by serum ferritin levels > 2,000 mg/l or liver iron concentration > 4 mg/g liver dry weight, (3) > 6 years of age and (4) informed consent.
• Patients were prescribed a total daily dose of 75mg/kg of deferiprone.
• Efficacy was assessed by repeated serum ferritin measurements over the course of the study.
• Safety was assessed by analyzing the ALT levels over time after the baseline values were recorded. The occurrence of neutropenia, agranulocytosis and other adverse events were monitored.
• For purposes of analysis, patients were classified according to the following segments.
  • Splenectomy status (splenectomized/not splenectomized)
  • Age (under 18 years/ over 18 years)
  • Ferritin levels (FL) three classes (FL < 2,000 mg/l, 2,000 £ FL < 4,000 mg/l, FL ³ 4,000 mg/l)
  • ALT levels three classes (ALT < 60 U/l, 60 £ ALT < 150 U/l, ALT ³ 150 U/l).

Results – Efficacy: Ferritin levels dropped significantly for the overall group of patients.

There was a continuous decline in serum ferritin levels and the difference from baseline reached statistical significance (p = 0.01) at 36 months. A stratified analysis of the subgroups according to the classes of basal ferritin levels showed that the decrease was significant at all time points (12, 24, 36 months) for the subgroup of patients with > 4,000 mg/l at initiation of therapy. The decrease was significant after 24 months of therapy for the group with 2,000 £ FL < 4,000 mg/l at the initiation of therapy.



Results – Safety: The frequency of adverse events with the use of deferiprone was less than previously reported.

Agranulocytosis was observed in 5 patients. All five cases of agranulocytosis resolved upon discontinuation of therapy with deferiprone. Gastrointestinal problems, including nausea, vomiting and abdominal pain, were more frequent at the onset of therapy and resolved on average within 11 days of onset, generally without discontinuation of therapy.

Results
No statistically significant differences in ALT levels emerged after therapy with deferiprone. ALT levels transiently increased in some patients but no significant changes were observed after 24 months of therapy. As a result of elevated ALT values in some patients, therapy was temporarily interrupted for 8 patients and discontinued in 4 cases. 

Conclusions

• The Italian Registry for Controlled Use of Deferiprone represents, to date, the largest prospective clinical study for the evaluation of deferiprone.
• Results showed that deferiprone is an effective orally active iron chelator.
• The frequency of adverse events associated with deferiprone use were less than previously reported
• Younger, non-splenectomized patients with a higher risk of neutropenia should monitor their blood cell counts closely.

• If you would like to read the entire Ceci study (external site), click here.

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