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Combined tenofovir therapy reduces HBV antigens better than monotherapy

Combined pegylated-interferon alpha 2b with tenofovir therapy for hepatitis B was safe in patients positive for HBV e-antigen and resulted in a greater reduction of HBeAg and HBV surface antigen compared with tenofovir monotherapy, according to recently published data.

“Monotherapy with [pegylated-interferon alpha 2b] or tenofovir has limited efficacy in HBeAg positive chronic hepatitis B. Combination therapy with [pegylated-interferon alpha 2b] and tenofovir may improve serological response rates,” Ankur Jindal, MD, MBBS, from the Institute of Liver and Biliary Sciences, India, and colleagues wrote. “Viral load reduction followed by immune modulation is a potentially useful approach. This approach may reduce the relapse, increase off-treatment response and may therefore facilitate the discontinuation of [nucleos(t)ide analogues].”

The study comprised 53 patients who received tenofovir monotherapy and 53 patients who received tenofovir with pegylated-interferon alpha 2b added from 12 weeks to 36 weeks, after which all patients continued tenofovir monotherapy until end of follow-up at 72 weeks. One patient from each group discontinued before end of follow-up.

At end of the follow-up, significantly more patients who received pegylated-interferon alpha 2b reached the primary endpoint of HBeAg loss (35.8% vs. 17%; OR = 2.73; 95% CI, 1.09-6.79). However, no patient in either group achieved HBeAg seroreversion.

Rates of HBV DNA loss (77.4% vs. 71.7%), alanine aminotransferase normalization (62.3% vs. 52.8%) and sustained virological response (20.8% vs. 11.3%) were comparable between the two groups at 72 weeks.

At 36 weeks, however, significantly more patients who received pegylated-interferon alpha 2b had more than 3 log HBV DNA reduction (92.5% vs. 66%; P = .001) and pegylated-interferon alpha 2b correlated significantly with HBeAg loss at 72 weeks (OR = 0.36; 95% CI, 0.15-0.91).

At 72 weeks, three patients who received pegylated-interferon alpha 2b achieved HBsAg loss and one of those achieved HBsAg seroconversion. None of the patients on tenofovir monotherapy achieved significant HBsAg loss.

Combined pegylated-interferon alpha 2b and tenofovir therapy was generally well tolerated. Adverse effects occurred most frequently among those with pegylated-interferon alpha 2b combined therapy, though the cumulative frequency of reported adverse events was comparable at 72 weeks.

“As high viral load in [chronic hepatitis B] leads to impaired T-cell responsiveness to various HBV proteins, a 12-week short course of tenofovir before add-on [pegylated-interferon alpha 2b] therapy restores the specific T-cell responsiveness by reducing the HBV load resulting in higher frequency of HBeAg loss and SVR,” the researchers concluded. “Further studies are required to identify if this sequential therapy would allow more patients to achieve and sustain HBsAg loss.” – by Talitha Bennett

Disclosure: The authors report relevant financial disclosures.