SNOWMASS, COLO. — Screening for both hepatitis C and B is a reasonable strategy in all patients who are under consideration for any disease-modifying antirheumatic drug. “If they turn out to be infected, you've done them a huge favor. Send them to a hepatologist for treatment,” advised Dr. Leonard H. Calabrese.
And just because they have chronic viral hepatitis doesn't mean that their comorbid rheumatic disease can't be aggressively treated, provided they don't have decompensated liver disease and are Child-Pugh class A, he stressed at a symposium sponsored by the American College of Rheumatology.
In fact, there is evidence to suggest that in the setting of chronic HCV, anti–tumor necrosis factor (anti-TNF) therapy is not only safe, it actually may also substantially improve the tolerability of antiviral therapy with interferon and ribavirin, thereby boosting the hepatitis cure rate, according to Dr. Calabrese.
This possibility was first broached a half-decade ago in a positive double-blind, placebo-controlled, phase II study of etanercept (Enbrel) (J. Hepatol. 2005;42:315-22). The manufacturer resisted hepatologists' subsequent pleas to mount a definitive clinical trial. However, such a study is now underway using another anti-TNF drug, infliximab (Remicade).
The 52-week, multicenter, blinded, randomized PARTNER (Pegylated Interferon Ribavirin and Anti-TNF Enhanced Response) trial, sponsored by the Cleveland Clinic, has completed just over half of its enrollment. Eligibility is restricted to patients with chronic HCV with genotype 1, the most treatment-resistant form of the liver disease. As in the etanercept study, these hepatitis C patients don't have concomitant rheumatic disease; they are being randomized to anti-TNF therapy solely in an effort to improve the results of their antiviral regimen.
However, several reports published in the rheumatology literature point to the safety of anti-TNF therapy in patients with chronic HCV and comorbid rheumatic diseases. Dr. Calabrese highlighted what he termed a “thoughtful and reassuring” seven-center prospective Italian series involving 31 chronic HCV-infected patients with rheumatoid arthritis (RA) refractory to nonbiologic disease-modifying antirheumatic drugs (DMARDs). After a mean 22 months of treatment with infliximab, etanercept, or adalimumab, the patients showed marked lessening of their rheumatic disease with no adverse effects on liver enzymes or HCV viral load (J. Rheumatol. 2008;35:1944-9).
Based largely on such favorable reports as well as the results of the earlier etanercept study, Dr. Calabrese reported that he turns to anti-TNF biologic agents as first-line therapy in HCV-infected patients who require remittive therapy for a rheumatic disease. He makes sure they have a baseline liver biopsy, carefully monitors their liver enzymes, and considers rebiopsy at 3-5 years.
“At this point in time, there are more data on the safety of biologics than nonbiologic DMARDs in the setting of HCV,” said Dr. Calabrese, who is professor of medicine at the Cleveland Clinic Foundation.
The use of DMARDs in patients with chronic HBV is a considerably more complex issue. That's because there is evidence that any form of immunosuppressive therapy—biologics, older DMARDs, or moderate- or high-dose systemic corticosteroids—can trigger a severe or even fatal flare of hepatitis B if the therapy is interrupted or discontinued.
Nonetheless, there are multiple reports of HBV-infected patients who are being successfully treated for rheumatoid arthritis and other rheumatic diseases with biologic agents or conventional DMARDs, provided they are started on prophylactic antiviral therapy beforehand. For example, Italian investigators reported no cases of HBV reactivation in 20 patients with rheumatic diseases who were treated with biologic DMARDs during a median 19 months of prophylactic antiviral therapy with lamivudine at 100 mg/day (Reumatismo. 2008;60:22-7).
Today, there are much better antivirals than lamivudine for this purpose, Dr. Calabrese pointed out. Nucleotide analog reverse transcriptase inhibitors such as adefovir (Preveon) and tenofovir (Viread) are very easy to use and have far fewer resistance issues. The experience to date strongly suggests that the newer agents can be given for the patient's full remaining life span.
There are at present no consensus guidelines in rheumatology that address screening for HCV and HBV. Dr. Calabrese advocated screening liberally; these are two of the biggest public health problems of the era, and treatment has progressed rapidly. He believes that all candidates for DMARD therapy ought to be screened, because at present there aren't enough data to say for sure that any of these agents are safe in the setting of viral hepatitis.
He also encouraged the screening of any rheumatology patient who is at high risk for HCV or HBV. For HBV, that would include anyone who's sexually active. For HCV, the high-risk population includes injectors of illegal drugs, individuals who engage in high-risk sexual activity, and anyone who received a blood transfusion before 1992.