Safety of antitumour necrosis factor (anti-TNF) therapy in patients with chronic viral infections: hepatitis C, hepatitis B, and HIV infection

Abstract

Tumour necrosis factor alpha (TNFalpha) is a pivotal cytokine in host defences with broad ranging effects on the innate and adaptive immune systems. Clinically, TNFalpha inhibitors have demonstrated remarkable efficacy in a wide range of autoimmune and inflammatory disorders but clearly at the cost of heightened susceptibility to a variety of infections in those treated with these agents. Most reports to date have described increased susceptibility to intracellular pathogens in patients with underlying chronic viral infections, but little in the way of adverse event reporting in these patients has occurred. While the reported experience to date is rather limited, TNFalpha inhibitors have displayed a reasonable safety profile in the setting of some chronic viral infections and in certain circumstances have demonstrated adjunctive activity in the treatment of these infections. Given the high prevalence of chronic viral infections in patients who are candidates for anti-TNF therapy and the potential for these agents in the treatment of chronic viral illness, additional studies are urgently needed to assess the risks and benefits of such therapy in these populations.

Figure 1

A 58 year old woman with severe seropositive rheumatoid arthritis and chronic hepatitis B infection (HBeAg negative) was treated initially with methotrexate (MTX, 15 mg per week) and low dose prednisolone (<7.5 mg per day) without significant improvement of the joint disease. During treatment the hepatitis B infection exacerbated and was successfully managed with antiviral therapy (lamivudine 100 mg per day) and discontinuation of MTX and corticosteroids. After biochemical and virological remission was achieved, the patient was given infliximab (INFL, intravenous 3 mg/kg every eight weeks) for approximately six months. Despite the absence of hepatitis flare, infliximab was replaced with etanercept (ETN, 25 mg subcutaneously twice a week) due to resistant joint disease. The patient had a partial response to this regimen and she is still receiving etanercept and lamivudine without any evidence of biochemical or virological relapse. HBV DNA was measured with the Amplicor HBV monitor assay (Roche Molecular Systems, Nutely, NJ; sensitivity: 400 copies/ml). ALT, alanine aminotransferase.