RANDOMIZED CONTROLLED TRIAL OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR FOR THE TREATMENT OF CHRONIC HEPATITIS C

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously to 45 chronic hepatitis C patients, randomly assigned to receive 0.5, 1 or 2μg GM-CSF/kg b.w. daily/6 weeks (n=30), or no treatment (n=15). Alanine transaminase (ALT) values normalized in four out of 10 (40%) patients administered 2μg GM-CSF [1 cleared hepatitis C virus (HCV) RNA] but in none given 0.5 or 1μg or untreated controls (P=0.0079). Following 4 weeks of rest, patients received 5 million units of interferon (IFN)α2b every other day/6 months, alone (n=30), or combined with 2μg 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/IFNα2b combination (mean log HCV RNA copies/ml±SEM: 4.13±0.40 vs 5.29±0.23;P=0.011), and in 20/30 (67%) receiving IFNα2b 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 2μg dose). 2-5AS increased more in the GM-CSF/IFN-α2b combination than with IFNα2b 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/IFNα2b combination has an additional—but transient—antiviral activity in chronic hepatitis C.