Randomized controlled trial of recombinant human granulocyte-macrophage colony-stimulating factor for the treatment of chronic hepatitis C

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously to 45 chronic hepatitis C patients, randomly assigned to receive 0.5, 1 or 2 mu g GM-CSF/kg b.w. dialy/6 weeks (n=30), or no treatment (n=15), Alanine transaminase (ALT) values normalized in four out of 10 (40%) patients administered 2 mu g GM-CSF [1 cleared hepatitis C virus (HCV) RNA] but in none given 0.5 or 1 pg or untreated controls (P=0.0079). Following 4 weeks of rest, patients received 5 million units of interferon (IFN)alpha 2b every other day/6 months, alone (n=30), or combined with 2 mu g GM-CSF/daily for 3 months (n=15), At treatment end, ALT levels in patients administered the combination normalized more frequently than in those given monotherapy (73% vs 47%, P=0.089). Viraemia decreased significantly in 11/15 (73%) patients administered GM-CSF/IFN alpha 2b combination (mean log HCV RNA copies/ml +/- SEM: 4.13 +/- 0.30 vs 5.29 +/- 0.23; P=0.011), and in 20/30 (67%) receiving IFN alpha 2b monotherapy (4.27 +/- 0.28 vs 5.31 +/- 0.14; P=0.004); 27% and 20% of patients given the combination and monotherapy, respectively, cleared HCV RNA, One patient in each regime had a sustained response after 12 months, 2',5'-Oligoadenylate synthetase activity (2-5AS) increased during GM-CSF therapy (P=0.033 with the 2 mu g dose). 2-5AS increased more in the GM-CSF/IFN alpha 2b combination than with IFN alpha 2b monotherapy (P<0.02). GM-CSF provoked a skin reaction at the injection site, accompanied by moderate and reversible rises in eosinophil and leucocyte counts, In summary, daily s.c. GM-CSF administration is safe and shows effects against HCV; the GM-CSF/IFN alpha 2b combination has an additional-but transient-antiviral activity in chronic hepatitis C. (C) 2000 Academic Press.