Long-term safety and efficacy of deferasirox (Exjade®) for up to 5years in transfusional iron-overloaded patients with sickle cell disease

Elliott Vichinsky, Françoise Bernaudin, Gian Luca Forni, Renee Gardner, Kathryn Hassell, Matthew M. Heeney, Baba Inusa, Abdullah Kutlar, Peter Lane, Liesl Mathias, John Porter, Cameron Tebbi, Felicia Wilson, Louis Griffel, Wei Deng, Vanessa Giannone, Thomas Coates

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4±6·3mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4years deferasirox exposure significantly decreased by -591μg/l (95% confidence intervals, -1411, -280μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4years.

Original languageEnglish (US)
Pages (from-to)387-397
Number of pages11
JournalBritish Journal of Haematology
Volume154
Issue number3
DOIs
StatePublished - Aug 1 2011

Fingerprint

Sickle Cell Anemia
Iron
Safety
Deferoxamine
Chelation Therapy
Lost to Follow-Up
Ferritins
Chelating Agents
deferasirox
Drug-Related Side Effects and Adverse Reactions
Nausea
Diarrhea
Creatinine
Reference Values
Maintenance
Research Personnel
Confidence Intervals
Kidney
Serum

Keywords

  • Deferasirox
  • Exjade
  • Iron overload
  • Oral iron chelator
  • Sickle cell disease

ASJC Scopus subject areas

  • Hematology

Cite this

Long-term safety and efficacy of deferasirox (Exjade®) for up to 5years in transfusional iron-overloaded patients with sickle cell disease. / Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M.; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas.

In: British Journal of Haematology, Vol. 154, No. 3, 01.08.2011, p. 387-397.

Research output: Contribution to journalArticle

Vichinsky, E, Bernaudin, F, Forni, GL, Gardner, R, Hassell, K, Heeney, MM, Inusa, B, Kutlar, A, Lane, P, Mathias, L, Porter, J, Tebbi, C, Wilson, F, Griffel, L, Deng, W, Giannone, V & Coates, T 2011, 'Long-term safety and efficacy of deferasirox (Exjade®) for up to 5years in transfusional iron-overloaded patients with sickle cell disease', British Journal of Haematology, vol. 154, no. 3, pp. 387-397. https://doi.org/10.1111/j.1365-2141.2011.08720.x
Vichinsky, Elliott ; Bernaudin, Françoise ; Forni, Gian Luca ; Gardner, Renee ; Hassell, Kathryn ; Heeney, Matthew M. ; Inusa, Baba ; Kutlar, Abdullah ; Lane, Peter ; Mathias, Liesl ; Porter, John ; Tebbi, Cameron ; Wilson, Felicia ; Griffel, Louis ; Deng, Wei ; Giannone, Vanessa ; Coates, Thomas. / Long-term safety and efficacy of deferasirox (Exjade®) for up to 5years in transfusional iron-overloaded patients with sickle cell disease. In: British Journal of Haematology. 2011 ; Vol. 154, No. 3. pp. 387-397.
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abstract = "To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4±6·3mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5{\%} completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8{\%}), lost to follow-up (9·2{\%}) and adverse events (AEs) (7·6{\%}). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6{\%}), diarrhoea (10·8{\%})], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4years deferasirox exposure significantly decreased by -591μg/l (95{\%} confidence intervals, -1411, -280μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4years.",
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