Adherence with telaprevir BID vs. q8h dosing in treatment-naive HCV-infected patients: Results from the phase III optimize study.

Background and Aims: The OPTIMIZE study was a randomized, open-label, multicenter, Phase III study in treatment-naive patients with chronic genotype 1 HCV infection (NCT01241760). OPTIMIZE established the non-inferior efficacy of telaprevir (TVR, T) twice daily (bid) in combination with peginterferon/ribavirin (PR) compared with every 8 hours (q8h). In this retrospective analysis, TVR adherence and its association with virologic outcomes were explored. Method(s): 740 patients were randomized to either: TVR 1125mg bid or TVR 750mg q8h in combination with PR. The primary endpoint was SVR12 (HCVRNA <25 IU/mL after 12 weeks of followup). TVR adherence was measured using a patient-completed electronic diary (e-diary) that captured the amount and timing of TVR dosing relative to the prescribed regimen. Additionally, adherence to TVR and PR was measured by dispensed versus returned medications (pill count). Adherence was expressed as the percentage of prescribed doses during the treatment period and categorized by thresholds established from previous literature and from the distribution of adherence results from the current study. The e-diary analysis was performed using the intent-to-treat (ITT) population, where missing entries were considered as 0% adherent. Observed data analyses were also performed. Result(s): E-diary and pill count adherence data were available for 700 (95%) patients. Adherence results by treatment arm are provided in the table. Self-reported (e-diary) adherence rates were lower than those based on pill count data: this difference was more marked for ITT compared with observed analyses. Mean adherence was significantly greater by all three analysis methods for bid compared with q8h dosing. In a multivariate analysis, higher adherence was associated with greater odds of SVR12, irrespective of adherence measure (for example, <95% vs >=95% pill count: SVR12=69% vs 79%, OR = 1.86; 95% CI: 1.29, 2.69). Conclusion(s): Adherence based on patient electronic