CHICAGO – Data from two new trials, one in press and the other ongoing, suggest that two established tumor necrosis factor inhibitors may be the safest drugs for treatment of rheumatoid arthritis in a patient with active hepatitis C virus infection.
The recent pilot study (Journal of Hepatology, in press) of 50 patients with coexisting rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection clearly demonstrated that adding etanercept to traditional antiviral therapy was associated with clearing HCV and normalizing liver enzymes, Dr. Leonard H. Calabrese said at the Midwest Rheumatology Summit.
"This was kind of an opening salvo to us, saying, this is our drug. We should be looking at this ... to see if it’s an option to use to treat autoinflammatory disease and, in particular, rheumatoid arthritis," said Dr. Calabrese.
The ongoing Partner Trial is designed to answer the question of whether a tumor necrosis factor (TNF) inhibitor enhances antiviral responses to traditional therapy, specifically the efficacy of infliximab as an adjunct to peginterferon alfa-2b and ribavirin in the treatment of HCV genotype 1.
"One thing that is not a good idea is to use hepatotoxic drugs (like) methotrexate," said Dr. Calabrese.
Treatment is not the only challenge in caring for the patient with overlapping RA and HCV; just making the HCV diagnosis can be difficult.
"The most undiagnosed infection in our country is hepatitis C. There are probably about 3 million people walking around who are infected, who don't know it," said Dr. Calabrese, professor of medicine at the Cleveland Clinic’s Lerner College of Medicine at Case Western Reserve University. Most patients with undiagnosed hepatitis C have chronic infection, which is relatively asymptomatic, he said. "That’s why screening programs are essential."
He described a 49-year-old woman with a history of polyarthritis who presented for evaluation after a 7-month history of migratory arthritis involving feet, hands, wrists, and knees. The patient had a "fairly normal" hemogram and normal alanine transaminase (ALT) and was positive for the anti–cyclic citrullinated peptide (CCP) antibody.
"The most undiagnosed infection in our country is hepatitis C."
"So she clearly has rheumatoid arthritis ... and is an excellent candidate for methotrexate," he said. Lab results showed the woman to be positive for the HCV antibody, and negative for hepatitis B surface antigen and hepatitis B core antibody.
"So the question is, does this patient have active hepatitis C infection?" said Dr. Calabrese. And if so, how would that influence treatment decisions?
Nearly half of patients with chronic HCV have ALTs within the normal range, so the test has no negative predictive value. "The gold standard of diagnosis in HCV is the presence of fibrosis on liver biopsy," said Dr. Calabrese. "The reality is that if you have people with persistently normal ALT levels, upon biopsy, 75% have some evidence of damage, and about a third of them have advanced fibrosis."
This patient was found to have a normal ALT-38 u/mL, to have 1.2 million copies/mL of HCV-RNA, and to have genotype 1. Her liver appeared normal on ultrasound.
This patient has normal ALT but clearly has HCV, he said. "Normal liver enzymes do nothing at this juncture to tell us that this patient does not have a significant problem." While a biopsy is invasive, it has a very acceptable rate of complications, he said.
The alternative to biopsy is the transient elastography test, widely used in Europe. It is noninvasive and accurate, but not yet approved in the United States.
And the 49-year-old woman? "Patients such as this I would treat with a TNF-inhibitor monotherapy, and if that patient needs treatment, or my hepatologist says ‘I want to start this patient on therapy for hepatitis C next month’? Let’s do it – and keep them right on their TNF-inhibitor. We have enough data now to know that it’s probably a safe thing," he said.
Dr. Calabrese disclosed consultant and/or speaking income from Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genentech, Pfizer, and Roche. The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB.