Sir,. Dr von Wussow and colleagues (Sept 12, p 635) report neutralising recombinant interferon alpha 2a (rIFN-alpha 2a) antibodies (anti-IFN) in 5 of 25 treated patients with chronic myclogenous leukaernia. The presence of antibodies was associated with a lack of response or relapse during treatment.
In several trials we have treated 42 patients, who had chronic hepatitis B with high viral replication levels (HBV-DNA and HBeAg positive), with rIFN-alpha, administered intramuscularly at doses ranging from 2-5 to 20 MU/m2 of body surface, two or three times weekly over six months. Anti-IFN was measured monthly by a comparative ELISA and a biological neutralisation assay in serum samples obtained 75 h after the last dose of IFN.
Anti-IFN developed in 7 patients (17%). 1 patient (treated with 2-5 MU) lost HBV-DNA during the second month of therapy, had anti-IFN one month later, but remained HBV-DNA negative. A second patient (20MU) had anti-IFN one month after the start of treatment. At the second month, HBV-DNA became undetectable and the patient later seroconverted to ani-HBe. At the end of treatment, HBV-DNA became positive again, concomitantly with the highest anti-IFN level (titre 1/10 ). Finally, HBV-DNA became undetectable at the 15th month. During the fourth month of therapy, another patient (18 MU) had anti-IFN antibodies when HBV-DNA was still positive. This patient had a herpes zoster infection five months after the start of treatment, but the infection was not related to the anti-IFN levels. The other four patients, treated with 10, 10, 5, and 2-5 MU had serum antibodies at the second, third, fourth, and fifth months of therapy, respectively, when they were HBV-DNA positive; these patients did not lose their HBV-DNA.
Therapy was not discontinued in any patient despite the development of anti-IFN, and the symptoms due to interferon therapy (such as "flu-like syndrome" and weight loss) disappeared in the presence of anti-IFN. No patient had immune complex-associated illness.
The development of anti-IFN among patients who previously became HBV-DNA negative will not influence the response to treatment, but if HBV-DNA remains positive at that time, efficacy is usually poor. Thus it is advisable to stop interferon treatment in patients who become HBV-DNA negative after the development of anti-IFN, because increasing levels of such antibodies in serum are related to a risk of viral reactivation.