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Stopping TDF treatment after long term virologic
suppression in HBeAg-negative CHB: two cases
from an ongoing randomized, controlled trial
T Berg1, E Schott2, G Felten3, C Eisenbach4, T Welzel5,
T Warger6, L Gallo6, E Martins7 and M Biermer8
1Universita¨tsklinikum Leipzig, Germany, 2Charite-CVK, Germany,
3Gastroenterologische Gemeinschaftspraxis, Germany, 4Medizinische
Universita¨tsklinik Heidelberg, Germany, 5J.W. Goethe Universita¨t,
Germany, 6Gilead Sciences, Germany, 7Gilead Sciences, USA, 8Drs
Moeller, Heyne, Biermer, Germany
PURPOSE: Recent data suggest that long term suppression of
HBV DNA may lead to a reconstitution of the immune response
to HBV in some patients after stopping adefovir therapy
in HBeAg-negative patients (Hadziyannis et al. 44th Annual
Meeting of the European Association for the Study of the Liver
2009, April 22–26; p. S30, abstract 18). The viral relapse
seemed to boost immune response to HBV which was followed
by HBsAg clearance in approximately 1/3 of patients. The
FINITE CHB Study evaluates the controlled stopping of long
term tenofovir DF (TDF) therapy in virologically suppressed
HBeAg-negative patients to assess this concept.
METHODS: Eligible study subjects who had been on
effective TDF-containing therapy (TDF mono or TDF+LAM
or TDF+FTC) for at least 4 years are randomized to either
stop TDF at baseline or to continue TDF therapy. All
subjects will be followed for 144 weeks. Primary study
endpoint is HBsAg loss at Week 144. The protocol defines
criteria for restarting TDF in case the HBV relapse exceeds
acceptable limits. This open-label study is currently
enrolling patients at 15 sites in Germany (ClinicalTrials.
gov: NCT01320943). The study aims to enroll 90
HBeAg-negative patients in total.
RESULTS: Initial data from two subjects who stopped TDF
and have reached study visit Week 40 and Week 32,
respectively, are presented here. One study subject (Case A)
is currently maintaining HBV replication at low levels (Week
34: 24 IU/mL, Week 36: 34 IU/mL, Week 40: 182 IU/mL)
without TDF while having achieved normal ALT levels
(<45 IU/mL). The expected HBV flare had peaked at Week 6.
Notably HBsAg levels have been decreasing ()1.5 log); with
the sharpest drop occurring immediately post ALT-peak (Fig.
1A). In contrast, the second subject (B), after having flared
at study visit Week 8, demonstrated slow decline of HBV
DNA which turned into an increase and a second peak at the
Week 28 visit. TDF therapy was restarted and subsequently
HBV DNA fell rapidly while ALT levels normalized (Fig. 1B).
HBsAg levels had remained constant in this subject. Patients
who were randomised to the continuous TDF arm remain on
TDF therapy without any issues.
CONCLUSION: These two initial cases support the validity of
this investigational approach. While stopping TDF may induce
a flare and subsequent viral control, it also appears that
TDF can potentially be safely and effectively re-introduced if
required. This clinical trial will allow the study of the long
term outcome of patients and the investigation of prognostic
factors associated with off-therapy response.
Fig. 1 Both study subjects stopped TDF at baseline, HBV
DNA and ALT flared subsequently. Subject A) continues
without TDF having low level HBV DNA, normal ALT and
declining HBsAg while in subject B) TDF has been restarted
after a second flare which quickly reduced HBV DNA and
normalized ALT.
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发表于 2012-9-14 21:42
