Treatment side-effects
 

David Bernstein MD: Pegylated interferon and ribavirin is a therapy that has many side-effects. Patients therefore need to be monitored very closely. It's recommended that patients come in from the beginning of therapy at least every two weeks in the first month and then, at minimum, monthly after that for a total of 12 months.

Robert Brown MD: The side effect profile of the two pegylated interferon products are quite similar. There was a lower rate of depression reported in the pegylated interferon alpha-2a trial than in the pegylated interferon alpha-2b trial. However, the rate of discontinuation for serious adverse events related to neuropsychiatric symptoms was about the same. So I think at the current time, we cannot clearly establish a difference in side effect profiles between the two products.

David Bernstein MD: Interferon is associated with numerous potential side-effects. The most common ones that we see are flu-like illness, manifested by nausea or vomiting, fever, chills, headache, diarrhea. Most commonly, these symptoms are caught early in the therapy. They generally last one to two weeks, perhaps four weeks, and then usually resolve. There are a subset of patients who will have flu-like illness throughout the entire course of 48 weeks of therapy, and there are also a subset of patients that will have no flu-like symptoms at all right from the beginning of therapy.

Depression is a frequent complication of therapy, occurring anywhere to 30 to 50% of the time.

Discontinuation due to side-effects in the published clinical trials of pegylated interferon and ribavirin is about 20%. It's probably much higher in the general population now that these products are being used more frequently.

Robert Brown MD: The most common side-effects that lead to discontinuation of interferon are neuropsychiatric, in particular depression. Depression, if it can't be managed with antidepressants, rarely responds to dose reduction. And so your decisions have to be management of that side effect or stopping the medication.

David Bernstein MD: The side-effects profiles of pegylated interferon-ribavirin, when compared to standard three times a week interferon and ribavirin, are really similar. There are, however, two noticeable differences. There seem to be more injection site reactions with pegylated interferon than with standard interferon, and there seem to be significantly more episodes of neutropenia with pegylated interferon than with standard interferon.

The most common side-effects of ribavirin are the development of hemolytic anemia, in which patients will feel tired, and with significant anemia there are risks of development of heart disease. Patients can also develop rash, cough, insomnia and depression. In addition, ribavirin is highly teratogenic, and so patients have to be counseled appropriately that they cannot become pregnant or sire a child while on ribavirin or six months after stopping ribavirin.

Robert Brown MD: Dose discontinuation of ribavirin is actually uncommon. The major problem with ribavirin is anemia, and this can usually be managed with dose reduction. About a quarter of patients in the clinical studies required some form of ribavirin dose reduction. The majority of these were for symptomatic anemia.

Dose reductions occur in anywhere between 10 and 40% with standard interferon. The rate of dose reductions has actually increased over the past number of years while the rate of dose discontinuations has decreased, reflecting a difference in the approach to side effect management, emphasizing trying to continue with therapy even at lower doses, rather than stopping completely.