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

• Published in: Hepatology research Vol. 39; no. 5; pp. 455 - 462
• Main Authors: Rustgi, Vinod, Nelson, David R., Balan, Vijayan, Abelson, Robert D., Fiscella, Michele, Migone, Thi-Sau, Pulkstenis, Erik, Subramanian, G. Mani
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01-05-2009
• Subjects: albinterferon alfa-2b; B-lymphocyte stimulator; BLyS protein; chronic hepatitis C; Hepatitis C virus; pharmacokinetics
• ISSN: 1386-6346; 1872-034X
• DOI: 10.1111/j.1872-034X.2008.00475.x

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.