Changes in B-lymphocyte stimulator protein levels during treatment with albinterferon alfa-2b in patients with chronic hepatitis C who have failed previous interferon therapy

Aim: The pharmacodynamics of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon-α-2b genetically fused to human albumin, was evaluated in patients with chronic hepatitis C with a previous non-response to interferon-α-based therapy. B-lymphocyte stimulator (BLyS) is an essential in vivo regulator of B-lymphocyte homeostasis. This analysis examined the relationship between serum BLyS level and virologic response across a range of alb-IFN doses. Methods: In all, 115 patients were randomized initially to three alb-IFN treatment arms (900 and 1200 μg every two weeks [q2wk], and 1200 μg every four weeks) with weight-based ribavirin, followed by sequential enrollment in two higher dose arms (1500 and 1800 μg q2wk). Serum BLyS level was assessed by enzyme-linked immunosorbent assay. Results: Serum BLyS levels at baseline were lower in African-Americans (P < 0.001). Significant BLyS inductions were observed at weeks 12 and 24 versus pretreatment; in general, serum BLyS levels returned to pretreatment levels following treatment completion. Induction of BLyS was greater in the highest dose group; a significant dose-response trend was observed at weeks 12 (P = 0.002) and 24 (P < 0.001), as well as a significant time trend, with further BLyS induction increases at week 24 versus 12 (P < 0.001). Week 24 BLyS level change correlated with hepatitis C virus RNA reduction (r = -0.28; P = 0.006), driven primarily by patients with BLyS increases > 400%, but did not correlate with sustained virologic response. Conclusion: Higher alb-IFN doses demonstrated dose-related BLyS increases, although the correlation with virologic response was modest.