Boceprevir a useful option for patients who did not respond to earlier course of hepatitis C therapy

A regimen of boceprevir with pegylated interferon and ribavirin achieved cure rates of between 40 and 68% in patients who did not respond to a previous course of hepatitis C therapy, data presented to the 47th International Liver Congress in Barcelona last week show.

The addition of boceprevir to standard hepatitis C therapy (pegylated interferon/ribavirin) achieved a sustained virological response 24-weeks post treatment (SVR24) in 40% of individuals with a prior null response to treatment; in 56% of those who relapsed after an earlier course of therapy; and in 68% of patients with a prior partial response.

Factors associated with the success of treatment included baseline platelet count and viral load.

Boceprevir is a protease inhibitor which works directly against hepatitis C. Its use with standard therapy – pegylated interferon and ribavirin – has been shown to increase the chances of treatment-naive individuals achieving a sustained virological response to therapy.

However the treatment of individuals who have not responded successfully to standard therapy remains a challenge. There are hopes that directly acting antiviral agents such as boceprevir will provide important new therapeutic options.

Investigators therefore designed a study involving 164 patients who had previously received an unsuccessful course of pegylated interferon and ribavirin therapy. All had genotype-1 infection.

Approximately a third (31%) had a null response to prior treatment (viral load decrease below 2 log₁₀ copies iu/ml after twelve weeks); 51% had a partial response (greater than 2 log₁₀ copies iu/ml decrease at week twelve, but a detectable viral load at the end of treatment); and 15% had relapsed (undetectable viral load at end of therapy but rebounded subsequently).

The patients received four weeks of lead-in treatment with pegylated interferon and ribavirin, which was then combined with boceprevir (800mg three times a day), treatment lasting for a further 44 weeks. The study’s primary endpoint was the proportion of patients who achieved a sustained virological response (an undetectable viral load) 24 weeks after the completion of treatment.

Approximately two-thirds of the patients were men, their average age was approximately 50 years, and 10% had liver cirrhosis.

A total of 138 patients were included in the investigators’ final analysis. This included 53 patients who stopped treatment early: 32 for treatment failure; eleven because of side-effects; and ten for non-medical reasons.

Rates of treatment response differed according to earlier outcomes. Some 68% of patients with an earlier partial response achieved a sustained virological response. This compared to 56% of individuals who had relapsed after therapy and 40% of individuals with a previous null response.

Factors associated with a sustained virological response 24-weeks post-treatment in a multiple stepwise logistic regression analysis included previous response to treatment (null response: no vs yes; p = 0.0093); higher baseline platelet count (>200,000) (p = 0.0017); male sex (p = 0.009) and a lower baseline viral load (below 800,000 copies iu/ml vs above 800,000 copies iu/ml; p = 0.073).

Almost all patients (96%) reported side-effects and for 10% of patients these were serious. Treatment was discontinued by 7% of patients because of adverse events and a third required an adjustment in the dose of their medication. The most common side-effects included anaemia (48%), fatigue (47%), nausea (30%) and headache (27%).

Strategies for the management of anaemia included dose modification (26%), therapy with erythropoietin (40%) and transfusion (2%).

“Boceprevir with pegylated interferon/ribavirin is efficacious in all three types of non-response: relapsers, partial responders and null responders,” conclude the investigators. “The safety profile…was comparable to that previously reported.”