NEW YORK – Abatacept may be helpful for treating rheumatoid arthritis in patients with concurrent hepatitis B, as long as patients are also given antiviral prophylaxis to prevent reactivation of their infection, according to the results of a small retrospective study presented at a rheumatology meeting sponsored by New York University.
"RA therapy in hepatitis B patients is complex. Flare of disease following immunosuppression is the primary concern. The major risk of hepatitis B comes not during but following immunosuppression, where reactivation can lead to severe, even fatal, hepatitis," said Dr. Daniel Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.
In this study, 5 women and 3 men with RA were treated with abatacept and followed for a mean of 18 months. At baseline, all were positive for hepatitis B, as indicated by the presence of hepatitis B surface antigen (HBsAg), hepatitis B virus DNA greater than 20,000 IU/mL, or intermittently positive AST/ALT on liver biopsy. Six patients tested negative for hepatitis C. All patients had used disease-modifying antirheumatic drugs (DMARDs) previously, and 3 had previously used a biologic agent. At baseline, the mean DAS 28 (Disease Activity Score 28) was 5.
When abatacept treatment was initiated, four of the eight patients were already on antiviral therapy, with three patients on entecavir and one on tenofavir.
A statistically significant decrease in DAS 28 scores was seen in patients treated with abatacept plus an antiviral, compared with those not treated with the antiviral. The statistical differences developed slowly and became noticeable after 10-12 months of treatment; the response continued through the 18 months of follow-up. DAS 28 scores remained stable but did not improve in those treated with abatacept but not with an antiviral.
All four patients who did not receive antiviral prophylaxis had a reactivation of hepatitis B, as indicated by a more than 10-fold increase in hepatitis B virus DNA. In contrast, none of those who took antiviral medications had reactivation.
"There may be a place for abatacept when treating RA patients with hepatitis B. It must be used with background antiviral therapy and used continuously for a number of months. We are now doing a prospective, double-blind study," said Dr. Furst in discussing the recently published findings (Arthritis Care Res. 2012 March 5 [doi: 10.1002/acr.21654]).
As far as the use of other biologics, rituximab is probably contraindicated in patients with a history of hepatitis B, suggested Dr. Furst. Although there are not a lot of data to support this contraindication, the results of one study (J. Clin. Oncol. 2009;27:605-11) demonstrated reactivation of hepatitis B virus in 25% of lymphoma patients treated with rituximab plus cyclophosphamide, hydroxydoxorubicin, Oncovin (vincristine), and prednisone (CHOP), compared with no reactivation in those receiving CHOP alone, he said.
Dr. Furst said that he is reluctant to use tumor necrosis factor (TNF) inhibitors for RA patients with a history of hepatitis B. He said that he makes an exception in cases where hepatitis B is controlled, such as in patients who are negative for hepatitis B virus DNA.
Dr. Furst presented a literature review that identified 9 cases of hepatitis B reactivation in patients treated with TNF inhibitors, including 5 cases of severe illness. On the other hand, in a retrospective analysis of 67 HbsAg-positive patients, none of the patients experienced HBV activation. "I think the idea that TNF inhibitors will cause problems afterwards makes sense. I think they are tricky to use in patients with hepatitis B."
According to the World Health Organization, about 2 billion people worldwide have been infected with the hepatitis B virus, 350 million live with chronic infection, and 600,000 die each year due to the acute or chronic consequences of hepatitis B, such as liver cancer or cirrhosis. In Southeast Asia, 8%-10% of adults are chronically infected.
According to Dr. Furst, after exposure to the hepatitis B virus, 70% of people will develop acute hepatitis B but will remain asymptomatic. About 30% will have clinical symptoms, and 0.5%-1% will progress to fulminant hepatitis. Chronic infection occurs in 5%. "This means you probably have a good number of patients with some hepatitis B in their backgrounds. If you see many patients from Asia or South America, one really must screen for hepatitis B before starting the patient on biologics," he said.
Dr. Furst has received research funding from, been a consultant to, or served on the advisory boards of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor OrthoBiotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.