Tuesday, March 12, 2013

Do Futility Rules for HCV Triple Therapy Work?

Do Futility Rules for HCV Triple Therapy Work?

Apparently, yes. In a retrospective analysis, the rules had high validity for identifying patients unlikely to achieve SVR.

Although triple therapy with either telaprevir or boceprevir is more effective than combination therapy for hepatitis C virus (HCV) infection, it is associated with significantly higher incidence of adverse events and the development of resistant variants. Therefore, to minimize unnecessary drug exposure in triple-therapy regimens, the U.S. FDA implemented futility rules when approving their use. So, are the rules working?

To examine the validity of the current rule for the telaprevir-based regimen (to cease all therapy in treatment-naive or -experienced patients if HCV RNA level >1000 IU/mL at week 4 or 12 or detectable at week 24), investigators retrospectively analyzed data from the telaprevir phase 3 trials.

Patients with HCV RNA levels >1000 IU/mL at week 4 included 1.7% (14 of 844) of treatment-naive patients, 0.7% (1 of 138) of prior relapsers, 0 of 46 prior partial responders, and 14% (10 of 70) of prior null responders. None of these 25 patients achieved sustained virologic response (SVR; HCV RNA level <25 IU/mL at 24 weeks after last planned dose of study treatment). In 23 of the 25 patients, HCV RNA levels reached their lowest points before week 4 (by week 2 for most) and subsequently increased beyond week 4, which met the definition of viral breakthrough. Few patients (5 of 23) with HCV RNA levels >100 and 1000 IU/mL at week 4 achieved SVR.

Comment: This retrospective study validates the futility rules recommended for the current HCV triple regimens. Specifically, for the telaprevir-based regimen, none of the patients with HCV RNA levels >1000 IU/mL at week 4 achieved sustained virologic response, and nearly all of them were experiencing viral breakthrough by week 4. These futility rules seem to be effective in preventing unnecessary drug exposure and the development of resistant variants.

Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology March 8, 2013

Adda N et al. Futility rules for telaprevir combination treatment for patients with hepatitis C virus infection. Clin Gastroenterol Hepatol 2013 Feb; 11:193. (http://dx.doi.org/10.1016/j.cgh.2012.10.045)
Medline abstract (Free)

Full text http://www.cghjournal.org/article/S1542-3565(12)01386-9/fulltext

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