Abstract
Introduction: Although the direct measurement of iron from a liver biopsy is the reference standard method to determine liver iron concentration (LIC), results are highly unreliable in patients with advanced fibrosis and cirrhosis. As a result, chelation therapy is difficult to monitor in this patient population where effective chelation therapy may be critical. It is therefore important to assess parameters additional to LIC in order to accurately assess body iron in these patients.
Aim: To analyze the efficacy of chelation with deferoxamine (DFO) and the investigational once-daily, oral iron chelator deferasirox (DSX) in patients with advanced fibrosis participating in DSX registration studies.
Methods: A subgroup of patients from DSX Studies 0107 and 0108 were selected based on a staging result according to the Ischak scale of 5 (incomplete cirrhosis) or 6 (probable or definite cirrhosis), measured either at baseline or after 1 year of chelation therapy. The subgroup of patients with β-thalassemia participating in Study 0107 received DSX (n=26) or DFO (n=30). In Study 0108, the subgroup of patients with β-thalassemia unable to be treated with DFO (n=12) or patients with anemias other than β-thalassemia (n=7) were treated with DSX only. In both studies, patients received chelation therapy according to baseline LIC.
Results: In Study 0107, treatment with DSX or DFO led to a decrease in semi-quantitative tissue iron score (TIS) and LIC, which were paralleled by changes in serum ferritin.
TIS, LIC and serum ferritin in a subgroup of patients with advanced fibrosis and cirrhosis treated with DSX and DFO (Study 0107)
| . | TIS . | LIC, mg Fe/g dw . | Serum ferritin, ng/mL . | |||
|---|---|---|---|---|---|---|
| . | DSX (n=26) . | DFO (n=30) . | DSX (n=26) . | DFO (n=30) . | DSX (n=26) . | DFO (n=30) . |
| *Median (min, max) | ||||||
| Baseline* | 35.5 (4,39) | 34 (10,52) | 25.5 (2.4,45.9) | 19.5 (3.9,55.1) | 4195 (321,12646) | 4144 (653,15283) |
| Change from baseline* | −2 (−43,20) | −2 (−25,16) | −9.4 (−42.2,13.1) | −3.1 (−24.5,12.4) | −1269 (−7082,3609) | −951 (−8259,1264 |
| . | TIS . | LIC, mg Fe/g dw . | Serum ferritin, ng/mL . | |||
|---|---|---|---|---|---|---|
| . | DSX (n=26) . | DFO (n=30) . | DSX (n=26) . | DFO (n=30) . | DSX (n=26) . | DFO (n=30) . |
| *Median (min, max) | ||||||
| Baseline* | 35.5 (4,39) | 34 (10,52) | 25.5 (2.4,45.9) | 19.5 (3.9,55.1) | 4195 (321,12646) | 4144 (653,15283) |
| Change from baseline* | −2 (−43,20) | −2 (−25,16) | −9.4 (−42.2,13.1) | −3.1 (−24.5,12.4) | −1269 (−7082,3609) | −951 (−8259,1264 |
Similarly, in Study 0108, DSX treatment produced a decrease in all 3 parameters in patients with β-thalassemia or rare anemia.
TIS, LIC and serum ferritin in a subgroup of β-thalassemia and rare anemia patients with advanced fibrosis and cirrhosis (Study 0108)
| . | TIS . | LIC, mg Fe/g dw . | Serum ferritin, ng/mL . | |||
|---|---|---|---|---|---|---|
| . | β-thalassemia (n=12) . | Rare anemia (n=7) . | β-thalassemia (n=12) . | Rare anemia (n=7) . | -thalassemia β (n=12) . | Rare anemia (n=7) . |
| *Median (min, max) | ||||||
| Baseline* | 35 (4,48) | 41 (32,49) | 29.4 (3.8,37.4) | 26.3 (15,51.3) | 4813 (440,11698) | 2385 (1553,9099) |
| Change from baseline* | 2 (−19,27) | −3 (−20,1) | −1.6 (−18,9.9) | −10 (−13.9,8.8) | −986 (−4453,2131) | −1322 (−2609,1901) |
| . | TIS . | LIC, mg Fe/g dw . | Serum ferritin, ng/mL . | |||
|---|---|---|---|---|---|---|
| . | β-thalassemia (n=12) . | Rare anemia (n=7) . | β-thalassemia (n=12) . | Rare anemia (n=7) . | -thalassemia β (n=12) . | Rare anemia (n=7) . |
| *Median (min, max) | ||||||
| Baseline* | 35 (4,48) | 41 (32,49) | 29.4 (3.8,37.4) | 26.3 (15,51.3) | 4813 (440,11698) | 2385 (1553,9099) |
| Change from baseline* | 2 (−19,27) | −3 (−20,1) | −1.6 (−18,9.9) | −10 (−13.9,8.8) | −986 (−4453,2131) | −1322 (−2609,1901) |
Conclusions: Chelation therapy with DSX or DFO is effective in reducing iron overload in patients with advanced fibrosis and cirrhosis. The trends observed in TIS and LIC were closely mirrored by changes in serum ferritin, highlighting the validity of this method for monitoring chelation therapy in this population.
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