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Higher efficacy of pegylated interferon‐α2b add‐on therapy in hepatitis B envelope antigen‐positive chronic hepatitis B patients on tenofovir monotherapy
Author(s) -
Jindal Ankur,
Vyas Ashish Kumar,
Kumar Devesh,
Kumar Guresh,
Sharma Manoj Kumar,
Sarin Shiv Kumar
Publication year - 2018
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.13049
Subject(s) - medicine , pegylated interferon , hbeag , gastroenterology , hepatitis b , combination therapy , odds ratio , hepatitis b virus , hbsag , chronic hepatitis , immunology , virus , ribavirin
Aim Monotherapy with pegylated interferon‐α (Peg‐IFNα) or the nucleos(t)ide analogs (NA) currently approved for treating chronic hepatitis B (CHB) has limited efficacy. Studies on the combination of Peg‐IFNα/NA have shown conflicting results. We investigated whether sequentially adding on Peg‐IFNα to tenofovir enhances serological response rates. Methods Treatment‐naïve, hepatitis B envelope antigen (HBeAg)‐positive CHB patients with moderately elevated alanine aminotransferase (ALT; 48–200 IU/mL) were started on tenofovir (300 mg/day) and enrolled at week 12 in a 1:1 ratio to either receive Peg‐IFNα2b add‐on (1.5 μg/kg/week) from week 12 to 36 ( n = 53) or continue tenofovir monotherapy ( n = 53). Both treatment arms received tenofovir consolidation therapy until week 72. The primary end‐point was HBeAg loss at week 72. Results At week 72, the rate of HBeAg loss was higher in the Peg‐IFNα2b add‐on group (35.8%) compared to the tenofovir monotherapy group (17%) ( P = 0.028; odds ratio, 2.73, 95% confidence interval, 1.09–6.79), and considerably higher in patients with a baseline hepatitis B virus (HBV)‐DNA level >6 log IU/mL (32.6% vs 11.4%; P = 0.021). Rates of HBV‐DNA loss (77.4% vs 71.7%; P = 0.51), ALT normalization (62.3% vs 52.8%; P = 0.32), and sustained virologic response (20.8% vs 11.3%; P = 0.18) at week 72 were comparable between the two groups. Significantly more patients in the add‐on group had >3 log HBV‐DNA reduction at week 36 (92.5% vs 66%; P = 0.001). Four patients treated with Peg‐IFNα2b add‐on achieved hepatitis B surface antigen (HBsAg) loss compared with one patient receiving tenofovir monotherapy. Decline of HBV‐DNA of >2 log at week 4 led to higher HBeAg loss at week 72, independent of treatment arm. No patient had treatment‐related adverse effects requiring treatment discontinuation. Conclusions Twenty‐four weeks of Peg‐IFNα2b as an add‐on sequential regimen to tenofovir is safe and resulted in greater loss of HBeAg and HBsAg compared to tenofovir monotherapy in selected HBeAg‐positive patients. Viral load reduction followed by immune modulation is a potentially useful approach.