SWITCH OR ADD-ON PEGINTERFERON TO CHRONIC HEPATITIS
B PATIENTS ALREADY ON NUCLEOS(T)IDE ANALOGUE
THERAPY (SWAP STUDY): FINAL RESULTS
Seng Gee Lim1, Wei Lyn Yang2, Jason Pik Eu Chang3, Jeffrey
Ngu4, Yi -Lyn Jessica Tan5, Taufique Ahmed6, Yock Young
Dan7, Yin Mei Lee8, Guan Huei Lee8, Poh Seng Tan9, Wah
Wah Phyo10, Lay Wai Khin11, Chris Lee10, Amy Tay10 and Edwin
Chan12, (1)Gastroenterology & Hepatology, National University
Health System, (2)Dept of Gastroenterology, Tan Tock Seng
Hospital, (3)Duke-Nus Medical School, Singapore, (4)Dept
of Gastroenterology, Singapore General Hospital, (5)Dept of
Gastroenterology, Changi General Hospital, (6)Jerudong Park
Medical Centre, (7)Division of Gastroenterology & Hepatology,
National University Health System, Singapore, (8)Division of
Gastroenterology & Hepatology, National University Health
System, (9)Division of Gastroenterology and Hepatology,
National University Health System, Singapore, (10)Dept of
Medicine, Yong Loo Lin School of Medicine, (11)Perinatal
Audit and & Epidemiology Unit, Kandang Kerbau Hospital,
(12)Duke-Nus School of Medicine
Background: It is unclear whether add-on or switch to
peginterferon alpha (PEG) in patients on long term nucleos(t)
ide analogue (NA) therapy is more efficacious for HBsAg
loss, hence we conducted a randomised control trial(RCT) to
address this Methods: This was a multicentre RCT of addon[
AO] or switch[S] to PEG(pegintron, Merck, USA) for 48
weeks, versus continuing NA randomised 2:2:1 (clinicaltrial.
gov NCT01928511). Patients were enrolled from five public
hospitals in Singapore, approved by IRB(DSRB2012/01039)
Computer randomisation stratified patients by HBeAg status,
high/low genetic barrier NA, or fibroscan score. Eligibility:
HBsAg>6months, NA>12 months, compensated cirrhosis
and undetectable HBVDNA. Exclusions: telbivudine,
decompensated cirrhosis, significant co-morbidities. The
primary endpoint was a composite of qHBsAg>1log reduction
or HBeAg loss, and secondary endpoint was HBsAg loss
at week 72 A study size of 255 patients had a 80% power
to detect a 30% difference between AO/S versus NA
Analysis was by intention-to-treat(ITT) using SPSSv20
Results: A total of 253 (AO 78, S 79, NA 42) patients were
randomised. ITT analysis at week 72, found qHBsAg>1 log
(IU/ml) reduction in 18/99(18%) in AO, 21/103 (20%) in S
and 1/51(2%) in NA(p<0 05 vs NA) HBeAg loss occured in
5/29 (17%) in AO arm, 11/37 (30%) in S and 0% in NA(p=ns)
The primary endpoint occured in 31/99 (31%) in AO, 35/103
(34%) in S and 1/51(2%) in NA (p<0 0001 vs NA) HBsAg
loss was seen in 9/99 (10%)in AO, 8/103 (8%) in S and 0%
in NA (p=0 026 AO vs NA, p=0 041 S versus NA) Baseline
qHBsAg[bqHBsAg]<48IU/ml was a predictor of HBsAg loss
for AO while S had higher bqHBsAg <310 IU/ml as a predictor
of HBsAg loss (p=0.026). HBV reactivation was seen in 16/53
(30 2%) in S 1/51 (2%) in AO and 1/30 (3 3%) NA(p<0 004
in S vs AO or NA) On multivariate analysis, bqHBsAg(logIU/
ml),week 8 qHBsAg log difference from baseline, and
age were independent predictors of HBsAg loss with
AUROC=0 96 (0 93-0 997),p<0 001 There were 38(15 0%)
discontinuations/withdrawals during therapy(11 from adverse
events[AE]) 1511AEs, 14serious adverse events. There was
one death due to myocardial infarction The most common
AEs were interferon-related Conclusion: Final results of the
SWAP study showed no significant difference between S and
AO to NA, with bqHBsAg, week 8 qHBsAg difference and age
being independent predictors However, AO required a much
lower bqHBsAg to achieve HBsAg loss compared to S. 作者: StephenW 时间: 2019-10-24 20:03