Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression.
Clevudine is a pyrimidine analog with potent and sustained antiviral activity against HBV. In the present study, we evaluated the safety and efficacy of clevudine 30 mg daily for 24 weeks and assessed the durability of antiviral response for 24 weeks after cessation of dosing in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB). We randomized a total of 86 patients (3:1) to receive clevudine 30 mg (n = 63) or placebo (n = 23) daily for 24 weeks. We followed patients for an additional 24 weeks after withdrawal of treatment. The median changes in HBV DNA from baseline were -4.25 and -0.48 log(10) copies/mL at week 24 in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained after withdrawal of therapy, with 3.11 log(10) reduction at week 48. At week 24 and week 48, 92.1% and 16.4% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (<300 copies/mL). The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in the clevudine and placebo groups at week 24, respectively (P = 0.0006). ALT normalization in the clevudine group was well-maintained during the post-treatment follow-up period. The incidence of adverse events was similar in the 2 groups. No resistance to clevudine was detected during treatment.


CONCLUSIONS
A 24-week clevudine therapy was well-tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e-CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission.
Yoo
Byung Chul
BC
Sungkyunkwan University Samsung Medical Center, Seoul, South Korea.
Kim
Ju Hyun
JH
Kim
Tae-Hun
TH
Koh
Kwang Cheol
KC
Um
Soon-Ho
SH
Kim
Young Soo
YS
Lee
Kwan Sik
KS
Han
Byung Hoon
BH
Chon
Chae Yoon
CY
Han
Joon-Yeol
JY
Ryu
Soo Hyung
SH
Kim
Haak Cheoul
HC
Byun
Kwan Soo
KS
Hwang
Seong Gyu
SG
Kim
Byung-Ik
BI
Cho
Mong
M
Yoo
Kwon
K
Lee
Heon-Ju
HJ
Hwang
Jae Seok
JS
Kim
Yun Soo
YS
Lee
Young-Suk
YS
Choi
Sung-Kyu
SK
Lee
Youn-Jae
YJ
Yang
Jin-Mo
JM
Park
Joong-Won
JW
Lee
Myung-Seok
MS
Kim
Dae-Ghon
DG
Chung
Young-Hwa
YH
Cho
Se-Hyun
SH
Choi
Jong-Young
JY
Kweon
Young-Oh
YO
Lee
Heon Young
HY
Jeong
Sook-Hyang
SH
Yoo
Hee-Won
HW
Lee
Hyo-Suk
HS
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D001086:Arabinofuranosyluracil; D000410:Alanine Transaminase; C034935:clevudine