By Shreeya Nanda, Senior medwireNews Reporter
Combining tenofovir disoproxil fumarate (TDF) with pegylated interferon alfa-2a (PegIFN) may improve the chances of hepatitis B surface antigen (HBsAg) loss in patients with hepatitis B virus (HBV) infection, suggests a randomised trial.
This study provides direct evidence that increased serum HBsAg loss can be achieved by “combining 2 agents with different mechanisms of action for a finite treatment duration”, say Patrick Marcellin (University Paris-Diderot, Clichy, France) and colleagues in Gastroenterology.
The primary endpoint of HBsAg loss at week 72 was achieved by 9.1% of 186 chronic HBV patients randomly assigned to receive open-label TDF plus PegIFN for 48 weeks. This was significantly higher than the 0.0% rate recorded for the 185 patients treated with TDF alone for 120 weeks (p<0.001) and the 2.8% rate in the group of 185 patients given PegIFN alone for 48 weeks (p=0.003).
But the rate of serum HBsAg loss did not differ significantly between the 184 participants who received TDF plus PegIFN for 16 weeks followed by TDF monotherapy for 32 weeks (2.8%) and those treated with either agent alone. And a post-hoc exploratory analysis showed that the HBsAg loss rate was significantly lower in patients given the combination for 16 compared with 48 weeks (p=0.002).
Multivariate analysis showed that in addition to treatment with TDF and PegIFN, the variables associated with HBsAg loss were HBV genotype A, on-treatment alanine aminotransferase (ALT) levels higher than 10 times the upper limit of normal and a 1-log decline in HBsAg levels from baseline to week 12.
The most frequently observed side effects were headache, alopecia, pyrexia, fatigue and malaise, which the researchers say are all characteristic of PegIFN therapy. And they all occurred at a comparable rate across treatment arms, except malaise, which was observed more frequently among study participants who received the combination therapy for 48 weeks.
In an accompanying editorial, Brian McMahon (Alaska Native Tribal Health Consortium, Anchorage, USA) commends the authors on their well-conducted study, but points out that as only a small minority of patients achieved HBsAg loss, “patients offered this combination should be carefully selected and counseled”.
He suggests that the best candidate to discuss combination therapy with “would be a young person with no medical or mental health contraindications, who has no evidence of cirrhosis, infected with genotype A with a significant increase in ALT level, and who understands the side effects of IFN and is willing to tolerate those effects for 48 weeks.”
McMahon adds: “The patient should also understand that failure to respond to this regimen would likely mean that he or she would still need to be started on TDF or a nucleoside analogue.
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