Prime

Type your tag names separated by a space and hit enter

Efficacy of switching to telbivudine plus adefovir in suboptimal responders to lamivudine plus adefovir.

Abstract

AIM

To examine the efficacy of telbivudine (LdT) + adefovir (ADV) vs continuation of lamivudine (LAM) + ADV in patients with LAM-resistant chronic hepatitis B (CHB) who show a suboptimal response to LAM + ADV.

METHODS

This was a randomized, active-control, open-label, single-center, parallel trial. All eligible patients were enrolled in this study in Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea, between March 2010 and March 2011. Hepatitis Be antigen (HBeAg)-positive CHB patients whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo of LAM + ADV therapy were included. Enrolled patients were randomized to either switching to LdT (600 mg/d orally) plus ADV (10 mg/d orally) (LdT + ADV group) or to continuation with LAM (100 mg/d orally) plus ADV (10 mg/d orally) (LAM + ADV group), and were followed for 48 wk. One hundred and six patients completed the 48-wk treatment period. Serum HBV DNA, HBeAg status, liver biochemistry and safety were monitored at baseline and week 12, 24, 36 and 48.

RESULTS

The duration of prior LAM + ADV treatment was 18.3 (LdT + ADV) and 14.9 mo (LAM + ADV), respectively (P = 0.131). No difference was seen in baseline serum HBV DNA between the two groups [3.66 (LdT + ADV) vs 3.76 (LAM + ADV) log10 IU/mL, P = 0.729]. At week 48, although there was no significant difference in the mean reduction of serum HBV DNA from baseline between LdT + ADV group and LAM + ADV group (-0.81 vs -0.47 log10 IU/mL, P = 0.167), more patients in the LdT + ADV group had undetectable HBV DNA levels compared to those in the LAM + ADV group (30.2% vs 11.5%, P = 0.019). Three patients with LdT + ADV treatment and 2 patients with LAM + ADV treatment achieved HBeAg loss. The patients in both groups tolerated the treatment well without serious adverse events. The proportion of patients with estimated glomerular filtration rate ≥ 90 mL/min per 1.73 m(2) in the LdT + ADV group increased from 49.1% (26/53) at baseline to 58.5% (31/53) at week 48, while that in the LAM + ADV group decreased from 37.7% (20/53) at baseline to 30.2% (16/53) at week 48.

CONCLUSION

The switch to LdT + ADV in suboptimal responders to LAM + ADV showed a significantly higher rate of virologic response at week 48. These results suggest that LdT + ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.

    ,

    Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.

    ,

    Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.

    ,

    Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.

    ,

    Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.

    ,

    Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.

    Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.

    Source

    MeSH

    Adenine
    Administration, Oral
    Adult
    Aged
    Antiviral Agents
    Biomarkers
    DNA, Viral
    Drug Administration Schedule
    Drug Resistance, Viral
    Drug Substitution
    Drug Therapy, Combination
    Female
    Hepatitis B e Antigens
    Hepatitis B virus
    Hepatitis B, Chronic
    Humans
    Lamivudine
    Male
    Middle Aged
    Organophosphonates
    Patient Selection
    Prospective Studies
    Republic of Korea
    Thymidine
    Time Factors
    Treatment Failure
    Viral Load
    Young Adult

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24431895

    Citation

    TY - JOUR T1 - Efficacy of switching to telbivudine plus adefovir in suboptimal responders to lamivudine plus adefovir. AU - Park,Hana, AU - Park,Jun Yong, AU - Kim,Seung Up, AU - Kim,Do Young, AU - Han,Kwang-Hyub, AU - Chon,Chae Yoon, AU - Ahn,Sang Hoon, PY - 2013/06/09/received PY - 2013/09/14/revised PY - 2013/09/16/accepted PY - 2014/1/17/entrez PY - 2014/1/17/pubmed PY - 2014/7/6/medline KW - Antiviral resistance KW - Chronic hepatitis B KW - Lamivudine KW - Suboptimal response KW - Telbivudine SP - 7671 EP - 9 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 19 IS - 43 N2 - AIM: To examine the efficacy of telbivudine (LdT) + adefovir (ADV) vs continuation of lamivudine (LAM) + ADV in patients with LAM-resistant chronic hepatitis B (CHB) who show a suboptimal response to LAM + ADV. METHODS: This was a randomized, active-control, open-label, single-center, parallel trial. All eligible patients were enrolled in this study in Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea, between March 2010 and March 2011. Hepatitis Be antigen (HBeAg)-positive CHB patients whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo of LAM + ADV therapy were included. Enrolled patients were randomized to either switching to LdT (600 mg/d orally) plus ADV (10 mg/d orally) (LdT + ADV group) or to continuation with LAM (100 mg/d orally) plus ADV (10 mg/d orally) (LAM + ADV group), and were followed for 48 wk. One hundred and six patients completed the 48-wk treatment period. Serum HBV DNA, HBeAg status, liver biochemistry and safety were monitored at baseline and week 12, 24, 36 and 48. RESULTS: The duration of prior LAM + ADV treatment was 18.3 (LdT + ADV) and 14.9 mo (LAM + ADV), respectively (P = 0.131). No difference was seen in baseline serum HBV DNA between the two groups [3.66 (LdT + ADV) vs 3.76 (LAM + ADV) log10 IU/mL, P = 0.729]. At week 48, although there was no significant difference in the mean reduction of serum HBV DNA from baseline between LdT + ADV group and LAM + ADV group (-0.81 vs -0.47 log10 IU/mL, P = 0.167), more patients in the LdT + ADV group had undetectable HBV DNA levels compared to those in the LAM + ADV group (30.2% vs 11.5%, P = 0.019). Three patients with LdT + ADV treatment and 2 patients with LAM + ADV treatment achieved HBeAg loss. The patients in both groups tolerated the treatment well without serious adverse events. The proportion of patients with estimated glomerular filtration rate ≥ 90 mL/min per 1.73 m(2) in the LdT + ADV group increased from 49.1% (26/53) at baseline to 58.5% (31/53) at week 48, while that in the LAM + ADV group decreased from 37.7% (20/53) at baseline to 30.2% (16/53) at week 48. CONCLUSION: The switch to LdT + ADV in suboptimal responders to LAM + ADV showed a significantly higher rate of virologic response at week 48. These results suggest that LdT + ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/24431895/Efficacy_of_switching_to_telbivudine_plus_adefovir_in_suboptimal_responders_to_lamivudine_plus_adefovir_ L2 - http://www.wjgnet.com/1007-9327/full/v19/i43/7671.htm ER -