Eltrombopag enables initiation and completion of pegylated interferon/ribavirin therapy in Japanese HCV-infected patients with chronic liver disease and thrombocytopenia

Takumi Kawaguchi, Atsumasa Komori, Kunio Fujisaki, Shuhei Nishiguchi, Michio Kato, Hitoshi Takagi, Yasuhito Tanaka, Kazuo Notsumata, Eiji Mita, Hideyuki Nomura, Mitsushige Shibatoge, Koichi Takaguchi, Toshihiro Hattori, Michio Sata, Kazuhiko Koike, Takumi Kawaguchi, Atsumasa Komori, Kunio Fujisaki, Shuhei Nishiguchi, Michio Kato, Hitoshi Takagi, Yasuhito Tanaka, Kazuo Notsumata, Eiji Mita, Hideyuki Nomura, Mitsushige Shibatoge, Koichi Takaguchi, Toshihiro Hattori, Michio Sata, Kazuhiko Koike

Abstract

To investigate the efficacy of eltrombopag for the treatment of thrombocytopenia in patients with chronic hepatitis C, a phase II, single-arm, open-label study with a 9-week pre-antiviral phase was conducted, followed by a 48-week antiviral phase and a 24-week follow-up phase. The proportion of patients who achieved a platelet count threshold, the proportion of patients who maintained a platelet count >50,000/µl, sustained virological response (SVR) rates and safety parameters were evaluated. Of the 45 enrolled patients (median age, 59 years; median platelet count, 63,000/µl; 98% with Child-Pugh class A), 43 (96%) achieved the platelet count threshold during the pre-antiviral phase. A total of 13 patients (29%) experienced ≥1 adverse event (AE), of which headache and vomiting were the most common, and 41 patients (mostly receiving eltrombopag 12.5 mg or 25 mg) entered the antiviral phase, of which 36 (88%) maintained the platelet count threshold; no patient platelet count decreased below 25,000/µl. Nine patients (22%) achieved an SVR at the 24-week follow-up. Grade ≥3 AEs occurred in 25 patients (61%). A total of 8 serious AEs occurred in five patients (12%). No mortality, thromboembolic events (TEEs), or cataract progression were reported. Eltrombopag increased the platelet count in chronic hepatitis C virus-infected patients with cirrhosis and thrombocytopenia and enabled them to initiate and complete interferon-based antiviral therapy (NCT01636778; first submitted: July 05, 2012).

Keywords: chronic hepatitis C; chronic liver disease; eltrombopag; ethnic difference; pegylated interferon/ribavirin therapy; thrombocytopenia.

Figures

Figure 1.
Figure 1.
Study design. In the first phase of the study after screening, open-label eltrombopag was administered for up to 9 weeks until the platelet count increased sufficiently to enable initiation of the antiviral (pegIFN + RBV) treatment. In the second phase, eltrombopag was administered together with the antiviral treatment for a period of 48 weeks. The antiviral treatment consisted of either pegIFN α-2a/RBV or pegIFN α-2b/RBV; the treatment regimen was selected by the investigator. PegIFN, pegylated interferon; RBV, ribavirin; SVR, sustained virologic response.
Figure 2.
Figure 2.
Patient disposition. *Four patients were withdrawn in the pre-antiviral phase, three because of violation of the eligibility criteria and one due to lack of achievement of the pre-defined platelet count threshold.
Figure 3.
Figure 3.
Median platelet counts during the study. AV BL, anti-viral baseline; BL, baseline; FU, follow-up.

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