Abstract and Introduction
Abstract
Background Adherence to therapeutic regimens affects the efficacy of peginterferon alfa (P) and ribavirin (R) therapy in patients with chronic hepatitis C virus genotype 1.
Aim To determine if medication adherence impacts efficacy [sustained virological response (SVR)] with triple therapy that includes boceprevir (BOC) plus P/R.
Methods Adherence was determined in two Phase 3 clinical studies with BOC: SPRINT-2 (previously untreated patients) and RESPOND-2 (patients who failed previous therapy with P/R). Adherence to the assigned duration of the dosing regimen and adherence to the three times a day (t.d.s.) dosing interval of 7–9 h for BOC were assessed by the recording of data from patients' dosing diaries and by the amount of study drug dispensed and returned.
Results Most patients (63–71%) adhered to ≥80% of their assigned treatment duration and achieved SVR rates of 86–90%. In contrast, patients who adhered to <80% of their assigned treatment duration achieved SVR rates of 8–32% (P < 0.0001), particularly low in patients who failed previous therapy (SVR = 8–15%). Different rates of adherence (<60% to >80%) to the t.d.s. dosing interval (7–9 h) with BOC did not influence the SVR rates (SVR = 60–83%) with the exception of patients who failed previous treatment and adhered to <60% of the t.d.s. dosing interval with BOC (SVR = 48–50%; P = 0.005).
Conclusions The achievement of an SVR is more dependent on adherence to the assigned duration of treatment than adherence to the t.d.s. dosing interval with boceprevir. Adherence to >60% of t.d.s. dosing with boceprevir is important in patients who failed previous therapy.
Introduction
The observation that adherence to a protracted course of anti-viral therapy significantly affects outcomes was first convincingly established for HIV therapy. Shortly thereafter, with the development of more effective hepatitis C virus (HCV) anti-viral therapy and the realisation that sustained virological response (SVR) translated into cure, reports emerged that HCV genotype 1 individuals, who can be maintained on >80% of their peginterferon (P) and ribavirin (R) dosing for the specified duration of therapy, exhibited heightened rates of response.
The recent transition of standard of care from the dual P/R regimen to a triple therapy regimen that now includes an HCV NS3/4A protease inhibitor has once again changed the landscape of HCV anti-viral therapy, and has again incrementally increased the proportion of HCV-infected patients, both treatment-naïve and treatment experienced, who may achieve SVR. Moreover, the newer regimens allow for individualised care, such that those patients exhibiting more rapid virological decline may truncate their course of therapy from 48 weeks to roughly half that duration, with similar SVR rates.
With the advent of the triple therapy regimens has come an increased pill burden, which can result in patients being required to take 15–19 pills daily [for boceprevir (BOC)-based treatment depending on the dose of R] in addition to weekly P injections. In addition, any pills required for adverse event management and other daily chronic medication requirements only make the pill burden higher. Given the pill burden and other challenges related to triple therapy, we analysed the impact of adherence on SVR. We attempted to ascertain whether adherence to BOC-based therapy influences anti-viral responsiveness in the context of the SPRINT-2 (previously untreated patients) and RESPOND-2 (patients who failed previous therapy with P/R) clinical trials.