Clinical

Peg-interferon plus ribavirin effective for chronic hep C in youngsters

Last Updated: 2012-12-21 15:10:13 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Peg-interferon plus ribavirin is safe and effective in children and adolescents with chronic hepatitis C (HCV), Canadian researchers say.

But, one researcher told Reuters Health, the group's data show "that it can be used; not that it should be used."

The investigator, Dr. Curtis L. Cooper from the University of Ottawa, added, "In reality, few children develop advanced liver disease as a consequence of chronic HCV infection during their childhood."

Although the efficacy of peg-interferon and ribavirin against HCV is well established in adults, there is limited evidence in children and adolescents.

Dr. Cooper and colleagues used a comprehensive meta-analysis of data from eight clinical trials to examine the efficacy and safety of peg-interferon alpha-2a and alpha-2b in combination with ribavirin in children and adolescents with HCV.

The reported online December 12 in Clinical Infectious Diseases that more than two-thirds (70%) of patients achieved an early virological response (EVR), and 58% had a sustained virological response. Only 7% of patients subsequently relapsed.

For genotypes 1 and 4, EVR (64%) and SVR (52%) were lower than for genotypes 2 and 3 (82% and 89%, respectively).

Common adverse events included neutropenia (32%), leukopenia (52%), anemia (11%), injection site erythema (27%), pruritus (10%), and alopecia (13%).

Small growth inhibitions accompanied treatment, but most studies concluded that growth returned to normal after cessation of therapy. One randomized controlled trial, however, showed that height-for-age had not returned to baseline two years later in some patients.

Adverse events led to treatment discontinuation in only 4% of patients.

"In the rare instance where a child is identified to be progressing toward advanced liver disease from HCV (which is done after a complete work up by a physician with expertise in HCV), then our work demonstrates that peg-interferon and ribavirin can be used relatively safely and with a reasonable hope of cure," Dr. Cooper said. "Although not specifically addressed in our analysis, most would agree that the older the child the better."

"Another consideration is the fact that newer, all oral, better tolerated medications with improved efficacy will likely be available within the next two to three years (i.e., combination Direct Acting Antivirals- DAAs)," Dr. Cooper explained. "Most predict that combination DAA regimens will represent a better therapeutic option to current IFN-based standard of care therapy."

"Of course, these studies have been conducted almost entirely in adult populations," Dr. Cooper cautioned. "A key point that we would like to make is for well designed trials to be conducted pre-licensing in children for HCV drugs and other medications. This will protect children from the potential harm of exposure to drugs with little safety and efficacy data."

Two other pediatric HCV researchers weighed in on the question of how and when it's best to treat these children and adolescents.

Dr. Stefan Wirth from Universitaet Witten-Herdecke, Wuppertal, Germany told Reuters Health, "Peg-interferon-alpha2b in combination with ribavirin is an approved (FDA and EMA) treatment for children and adolescents older than three years of age. Peg-interferon-alpha2 a has been licensed by the FDA beyond five years of age. Thus the combination therapy can be considered as standard of care and can be routinely used. The best age for treatment is between five and 10 years."

"Treatment can be offered to children with genotype 1 older than three years of age," Dr. Wirth said. "It is a must for individuals with genotype 2 and 3. There is no need for treatment in younger children, because of side effects and a 10-15% likelihood for spontaneous viral elimination."

Dr. Joan Robinson from Canada's University of Alberta in Edmonton elaborated: "Reasons to treat now include the fact that successful treatment prevents progressive liver disease and markedly decreases the risk of hepatoma. Reasons to delay treatment include the fact that very few will develop cirrhosis or hepatomas during childhood, many children are needle-phobic, and adverse events such as fatigue or depression may have more long-term sequelae in a child who is trying to learn large amounts of new material and sort out their social life than in an adult."

She added, "For those with genotype 1, it seems sensible to wait until there is more data on use of boceprevir and telaprevir in children as addition of one of these direct-acting protease inhibitors increases the chance of cure."

"There is a tremendous need for further data in children," Dr. Robinson continued. "Those who treat children for HCV should ideally do this as part of a study. If this is not practical, careful follow-up of these children for adverse events is vital. Case series of treated children should be reported in the medical literature if possible."

SOURCE: http://bit.ly/Tdlg1F

Clin Infect Dis 2012.