title: Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression.
abstract: 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.
authors.affiliation: Sungkyunkwan University Samsung Medical Center, Seoul, South Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Tae-Hun
authors.initials: TH
authors.lastname: Kim
authors.forename: Kwang Cheol
authors.initials: KC
authors.lastname: Koh
authors.forename: Soon-Ho
authors.initials: SH
authors.lastname: Um
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Kwan Sik
authors.initials: KS
authors.lastname: Lee
authors.forename: Byung Hoon
authors.initials: BH
authors.lastname: Han
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
authors.forename: Joon-Yeol
authors.initials: JY
authors.lastname: Han
authors.forename: Soo Hyung
authors.initials: SH
authors.lastname: Ryu
authors.forename: Haak Cheoul
authors.initials: HC
authors.lastname: Kim
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Byun
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Hwang
authors.forename: Byung-Ik
authors.initials: BI
authors.lastname: Kim
authors.forename: Mong
authors.initials: M
authors.lastname: Cho
authors.forename: Kwon
authors.initials: K
authors.lastname: Yoo
authors.forename: Heon-Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jae Seok
authors.initials: JS
authors.lastname: Hwang
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Lee
authors.forename: Sung-Kyu
authors.initials: SK
authors.lastname: Choi
authors.forename: Youn-Jae
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jin-Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Joong-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Myung-Seok
authors.initials: MS
authors.lastname: Lee
authors.forename: Dae-Ghon
authors.initials: DG
authors.lastname: Kim
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.forename: Se-Hyun
authors.initials: SH
authors.lastname: Cho
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Young-Oh
authors.initials: YO
authors.lastname: Kweon
authors.forename: Heon Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Sook-Hyang
authors.initials: SH
authors.lastname: Jeong
authors.forename: Hee-Won
authors.initials: HW
authors.lastname: Yoo
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D001086:Arabinofuranosyluracil; D000410:Alanine Transaminase; C034935:clevudine