Background Biologics suppress hepatitis B virus (HBV) replication and play an important role in eradicating HBV by stimulating HBV-specific cytotoxic T-cell responses1. We found that HBV reactivates or flares after biologics therapy in patients with chronic hepatitis B infection and in those with inactive hepatitis B surface antigen (HBs-Ag)2. The guideline, prevention of immunosuppressive-induced reactivation of HBV infection, recommend nucleoside analogs for treating patients with rheumatoid arthritis (RA) who are positive for HBs-Ag. We describe six patients who underwent biological therapy with the nucleoside analog entecavir (ETV).
Objectives We aimed to determine the safety of biological therapy in patients with RA carrying hepatitis B by evaluating clinical characteristics and changes in serological and biological markers of HBV reactivation.
Methods Six patients with RA who screened positive for HBs-Ag were prescribed with ETV under the direction of a hepatologist when HBV-DNA levels decreased to <2.1 log copies/mL. The patients were also treated with infliximab (n = 1), etanercept (n = 2), adalimumab (n = 2) and tocilizumab (n = 1) (Table 1). We evaluated the disease activity score of RA (DAS28-ESR), HBV markers and genotype before starting treatment as well as changes in the amount of HBV-DNA, HBs-Ag and alanine aminotransferase (ALT).
Results The average age, duration of RA and DAS28-ESRat baseline was 54.7 years, 10.9 years and 5.51, respectively. The minimum HBs-Ag value is 12.2 and three patients had values over >2000 before starting ETV therapy. The pre-treatment values of HBV-DNA and ALT were 4.28 log copies/mL and 20.2 U/L, respectively. Reactivation of HBV was not confirmed during 2.1 years the patients were treated with these agents. Hepatitis B viral DNA was undetectable in five patients and <2.1 log copies/mL in one. The DAS28-ESR was 3.14 at final follow-up and disease RA activity remained low (Table 1).
Conclusions Antiviral prophylaxis protected against HBV reactivation in patients with RA, indicating that biologics are relatively safe for treating such patients. Biologics could serve as a useful treatment for hepatitis B carriers who are simultaneously prescribed with nucleoside analogs under the control of a hepatologist.
Ganem D, Prince AM. Hepatitis B virus infection-natural history and clinical consequences. N Engl J Med. 2004; 350:1118-29.
Tamori A, Koike T, Goto H, et al. Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts. J Gastroenterol. 2011; 46:556-64.
Disclosure of Interest M. Tada Grant/research support from: Japan Osteoporosis Foundation grant 2013, T. Koike Speakers bureau: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, A. Tamori: None Declared, T. Okano: None Declared, Y. Sugioka: None Declared, K. Mamoto: None Declared, K. Inui: None Declared, H. Nakamura: None Declared
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