Rapid Prediction of Treatment Futility of Boceprevir with Peginterferon-Ribavirin for Taiwanese Treatment Experienced Hepatitis C Virus Genotype 1-Infected Patients

<div><p>The efficacy and safety of the boceprevir (BOC)-containing triple therapy in Taiwanese treatment-experienced patients remains elusive. After 4 weeks of peginterferon/ribavirin lead-in therapy, patients with cirrhosis or previous null-response received triple therapy for 44 weeks; whereas others received 32 weeks of triple therapy followed by 12 weeks of peginterferon/ribavirin therapy. Patients with HCV RNA > 100 IU/mL at week 12 or with detectable HCV RNA at week 24 of treatment were viewed as futile. A total of 123 patients received treatment. The rates of sustained virological response (SVR) and relapse were 66.7% and 8.9%, respectively by using intention-to-treat analysis. Multivariate analysis revealed that factors associated with SVR included HCV-1b (odds ratio [OR]/ 95% confidence intervals [CI]: 19.23/1.76–525.15, P = 0.01), BOC adherence (7.69/1.55–48.78, P = 0.01), serum albumin (OR/CI:6.25/1.14–40.07, P = 0.03) levels and HCV RNA levels (OR/CI:0.34/0.12–0.79, P = 0.01). Twenty-six (21.1%) patients experienced severe adverse events (SAEs). Multivariate analysis revealed that APRI > 1.5 was the single factor associated with occurring SAEs (OR/CI: 3.77/ 0.97–14.98, P = 0.05). Merging the cut-off values of HCV RNA > 7 log IU/mL at baseline and HCV RNA > 6 log IU/mL at week 4 provided the earliest and best combing viral kinetics in predicting week 12/24 futility with the PPV of 100% and accuracy of 93.5%. HCV-1 treatment experienced Taiwanese patients treated with boceprevir-containing triple therapy in real world had comparable efficacy and safety profiles with those reported in clinical trials. Early viral kinetics before week 4 of treatment highly predicted futility at week 12 or 24 of treatment.</p></div

Accuracy of viral kinetics in predicting week 12/24 futility.

<p>Abbreviations: AUC, area under the curve; SEN, sensitivity; SPE, specificity; PPV, positive predictive value; NPV, negative predictive value; ACC, accuracy.</p

Treatment responses.

<p>Treatment responses.</p

Baseline factors associated with occurrence of serious adverse events.

<p>Abbreviations: ALT, alanine aminotransferase; Ccr, Creatinine clearance rate; APRI, aspartate aminotransferase-to-platelet ratio index.</p

Factors associated with SVR.

<p>*P<0.05.</p><p>Abbreviations: SVR, sustained virological response; BOC, Boceprevir; RBV, ribavirin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; Ccr, Creatinine clearance rate; OR, odds ratio; CI, confidence intervals.</p

Safety profile of boceprevir plus peginterferon/ribavirin triple therapy for HCV genotype 1 treatment experienced patients.

<p>* defined as dose missing during treatment</p><p>Abbreviations: AE, serious adverse event.</p

Characteristics of 123 chronic hepatitis C patients who failed previous interferon-based therapy.

<p>Abbreviations: HCV, hepatitis C virus; AST, aspartate aminotransferase; ALT, alanine aminotransferase.</p

Combined effects of viral kinetics in predicting week 12/24 futilities.

<p>Abbrviations: SEN, sensitivity; SPE, specificity; PPV, positive predictive value; NPV, negative predictive value; ACC, accuracy.</p

Factors associated with week 12 and week 24 futilities.

<p>Abbreviations: BOC, Boceprevir; RBV, ribavirin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; Ccr, Creatinine clearance rate; APRI, aspartate aminotransferase-to-platelet ratio index; OR, odds ratio; CI, confidence intervals.</p