Boceprevir, used in combination with peginterferon and ribavirin, achieved high rates of sustained virologic response in patients with hepatitis C who failed prior treatment with peginterferon and ribavirin alone, a new study has found.

The results, documented in both partial and null responders, are potentially practice-changing, according to Janet Nguyen, PharmD, BCPS, vice president of network strategy, at A-Med Health Care, Huntington Beach, Calif., who was not associated with the study. “This is the first time boceprevir has shown efficacy in null responders,” Dr. Nguyen said. Such patients, she noted, “are usually unlikely to respond to retreatment with an interferon-based therapy.”

The results were based on an interim analysis from PROVIDE, an ongoing, open-label study of patients who participated in the peginterferon and ribavirin control arms of Phase II and III studies of boceprevir (Victrelis, Merck) and who failed to achieve SVR. After treatment with the triple-drug regimen, SVR was achieved in 40% (19 of 47) of prior null responders (defined as <2 log10 decline in hepatitis C virus [HCV] RNA at treatment week 12 in the prior study), according to the study, which was presented in Barcelona, Spain at the International Liver Congress/annual meeting of the European Association for the Study of the Liver (EASL).

The triple-drug combination also was effective in prior partial responders/relapsers: 68% (62 of 91) of those patients achieved an SVR. The total proportion of patients in whom SVR was achieved was 59% (81 of 138), noted lead study researcher, Jean-Pierre Bronowicki, MD, PhD, of the University Henri Poincare of Nancy, in Vandoeuvreples-Nancy, France. Seven percent of patients discontinued treatment due to adverse events; 48% had anemia, 34% had dysgeusia and 22% had neutropenia, Dr. Bronowicki reported. The degree of interferon responsiveness after lead-in with peginterferon and ribavirin correlated with prior response and could help predict SVR for prior null responders, the researchers concluded.

Although impressed with the results, Dr. Nguyen offered a few caveats to keep in mind when evaluating the study. First and foremost, she noted, “the sample size is small.” Concerning the null responders who achieved SVR, she said, “This is giving patients a treatment option, but 40% is still low. I would like to see upwards of 60% to 70%.” Nevertheless, she said there was enough evidence “to start acting on it with patients who have tried and failed before. This gives us some data that there could potentially be efficacy.”

More Data on Boceprevir

A related study, presented in a poster (1141) at EASL by Cooper et al, addressed the absence of head-to-head clinical trials between boceprevir and telaprevir (Incivek, Vertex). The researchers used an indirect comparison meta-analysis and meta-regression of the current evidence to evaluate the relative efficacy of the two drugs in combination with peginterferon-alfa and ribavirin. Included were Phase II and III randomized placebo-controlled trials evaluating the efficacy of boceprevir or telaprevir in adult patients infected with HCV genotype 1; four boceprevir trials and six telaprevir trials met inclusion criteria.

No significant differences were found between boceprevir and telaprevir in SVR among treatment-naive patients (relative risk [RR], 1.14; 95% confidence interval [CI], 0.93-1.37; P=0.20) or treatment-experienced patients (RR, 0.80; 95% CI, 0.18-3.45; P=0.30). Nor were there significant differences between boceprevir and telaprevir in relapse or in discontinuation of therapy among both groups. Boceprevir and telaprevir were shown to be comparable in efficacy, whether with standard-dose therapy durations or response-guided therapy durations. Among treatment-naive response-guided patients, telaprevir was associated with increases in rash (RR, 1.43; P=0.01) and pruritus (RR, 1.49; P=0.001), whereas boceprevir was associated with increased neutropenia (RR, 1.46; P=0.05).

Asked to comment on the method used in this study, Steven D. Pearson, MD, MSc, FRCP, president of the Institute for Clinical and Economic Review, in Boston, said that it had some merit. “Indirect comparisons can be ‘valid’ if the technique is well done,” he said. “Many coverage decisions require indirect comparisons. They are more open to question than direct comparisons, but often direct comparisons are not available or even feasible.”

The researchers noted that dosing schedule and side-effect profiles are key factors that allow for differentiation between the drugs—a point echoed by Dr. Nguyen. “Telaprevir has a much easier dosing schedule compared with boceprevir, with a three-month duration [compared with six to eight months for boceprevir] and one less blood draw,” she said. As for side effects, she noted that the study “called out the most significant [adverse reactions]—rash for telaprevir and neutropenia for boceprevir.”

Helping patients manage those adverse reactions can have a positive effect on compliance, Dr. Nguyen stressed. That in turn can be a cost-saver—“these are expensive drugs,” she noted. “But they have the potential for curing hepatitis C. So the role you can play as a pharmacist with patients’ adherence to therapy can save their lives.”

by George Ochoa