Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials

Abstract

Sustained virologic response at posttreatment Week 12 (SVR12) is the widely accepted efficacy endpoint for direct‐acting antiviral agents. Those with hepatitis C virus (HCV) are presenting younger with milder liver disease, potentially reducing need for long‐term liver posttreatment monitoring. This analysis aimed to determine the positive predictive value (PPV) of SVR at posttreatment Week 4 (SVR4) for achieving SVR12 in patients with HCV, without cirrhosis or with compensated cirrhosis, receiving glecaprevir/pibrentasvir (G/P) in clinical trials. An integrated dataset from 20 Phase 2 and 3 clinical trials of G/P was evaluated in patients with 8‐, 12‐ or 16‐week treatment duration consistent with the current label (label‐consistent group), and in all patients regardless of treatment duration consistency with the current label (overall group). Sensitivity analyses handled missing data either by backward imputation or were excluded. SVR4 PPV, negative predictive value (NPV), sensitivity and specificity were calculated for achieving SVR12 in both groups, and by treatment duration in the label‐consistent group. SVR was defined as HCV ribonucleic acid <lower limit of quantification. The label‐consistent group and overall group included 2890 and 4390 patients, respectively. PPV of SVR4 for SVR12 was >99% in both groups regardless of treatment duration. Not achieving SVR4 had 100% NPV and sensitivity for all groups. SVR4 measure had 79.5% specificity for identifying patients who did not achieve SVR12. Across 20 Phase 2/3 clinical trials of G/P, SVR4 was highly predictive of SVR12. Long‐term follow‐up to confirm SVR may not be necessary for certain populations of patients with HCV.

Four weeks of off‐treatment follow‐up is sufficient to determine virologic responses at off‐treatment week 12 in patients with hepatitis C virus infection receiving fixed‐dose pangenotypic direct‐acting antivirals

“…As expected, our findings demonstrated that the HCV RNA level at off‐treatment week 12 impeccably predicted the virologic response at off‐treatment week 24. This confirms that waiting for treatment response until 24 weeks is unnecessary, as the data strongly support the reliability of the off‐treatment week 12 assessment in predicting the virologic outcome at Week 24 11–17 …”

“…Reports from the phase II and III clinical trials employing fixed‐dose pangenotypic SOF/VEL and GLE/PIB for HCV indicated a >99% concordance between SVR 4 and SVR 12 . This outperformed reports from studies employing older generations of DAAs or IFN‐based therapies 15,16 . The duration of DAA treatment appeared to have no significant impact on concordance 16 .…”

“…15,16 The duration of DAA treatment appeared to have no significant impact on concordance. 16 However, a direct comparison regarding the performance of SVR 4 in predicting SVR 12 among real-world patients receiving various DAAs for HCV is lacking. Consequently, there is a crucial need for further research to confirm the role of serum HCV RNA levels at offtreatment week 4 for earlier determination of treatment outcomes in the era of fixed-dose pangenotypic DAAs.…”

Is dual testing for hepatitis C necessary? Modelling the risk of removing hepatitis C antibody testing for Australian blood donations

“…The assumption in the model is that anti‐HCV‐positive/NAT‐negative donations are infectious only for a limited period (see Figure 1 ) and a single donor does not constitute an ongoing transmission risk. This assumption is based on evidence that a single test at 12 weeks after treatment is adequate to be considered cured [ 20 ] and a high concordance of 12‐week results [ 21 ]. Australian donation guidelines have a 2‐week donation interval, and very few donors donate at the minimum interval.…”

Consensus recommendations on the management of hepatitis C in Australia's prisons

“…Testing to confirm cure (sustained virological response; SVR12), which is currently defined as undetectable plasma HCV RNA at least 12 weeks after treatment, is recommended. Recent data show that undetectable HCV RNA four weeks after treatment (SVR4) strongly predicts the SVR12 result 17,18 . Therefore, opportunistic testing of HCV RNA, potentially via point of care, at any time from four weeks (SVR4) after treatment completion is adequate, especially where release to the community may be imminent.…”