Effectiveness of triple therapy with direct-acting antivirals for hepatitis C genotype 1 infection: application of propensity score matching in a national HCV treatment registry

Abstract

Background: Observational studies are used to measure the effectiveness of an intervention in non-experimental, real world scenarios at the population level and are recognised as an important component of the evidence pyramid. Such data can be accrued through prospective cohort studies and a patient registry is a proven method for this type of study. The national hepatitis C (HCV) registry was established in Ireland in 2012 with the aim of monitoring the clinical and economic outcomes from new, high cost regimens for the treatment of HCV infection. A sustained virological response (SVR) 24 weeks following completion of therapy with interferon-containing regimens is considered a cure. Non-randomisation in these studies can result in confounding or selection bias. Propensity score (PS) matching is one of a number of statistical tools that can be used to mitigate the effects of confounding in observational studies.

Methods: We analysed the data of 309 patients who underwent triple therapy treatment with telaprevir (TPV) in combination with pegylated-interferon and ribavirin (PR) or boceprevir (BOC)/PR between June 2012 and December 2014. The decision to initiate treatment and the selection of the treatment regimen was at the discretion of the physician. To adjust for confounding, three approaches to propensity score matching were assessed Adjusted sustained-virological response rates (SVR), odds ratios, p-values and 95% confidence intervals were calculated from the three PS matched dataset.

Results: Prior to matching, the unadjusted sustained virological response rates 24 weeks after treatment complete (SVR24) were 74% (n = 158/215) and 61% (n = 57/94) for telaprevir/PR and boceprevir/PR, respectively. After matching, adjusted SVR24 rates were between 73-74% and 60-61% for telaprevir/PR and boceprevir/PR, respectively.

Conclusion: Efficacy rates were comparable with those reported in pivotal clinical trials and real world studies. After adjusting for confounding, we conclude that there was no difference in treatment effect after PS matching. The small sample size limits the conclusions that can be made about the effect of PS matching. Propensity score adjustment remains a tool that can be applied to future analysis, however, we suggest, where possible, using a larger sample size in order to reduce the uncertainty around the outcomes.

Keywords: Boceprevir; Comparative effectiveness; Outcomes Research; Propensity score matching; Protease inhibitor; Sustained virological response; Telaprevir.

Fig. 1

Flow diagram illustrating the outcomes of patients ever started on treatment with TPV/PR and BOC/PR. ^#Fifteen patients discontinued treatment prematurely but achieved a SVR24. Therefore, in total n = 215/309 (70%) (n = 200/222 and n = 15/87) achieved a SVR24

Fig. 2

Unadjusted treatment outcomes for the overall cohort and stratified per treatment regimen. # Fifteen patients discontinued treatment prematurely but achieved an SVR24; eleven patients treated with TPV/PR and four patients treated with BOC/PR. These patients were counted in both the discontinuation rate and the SVR rate

Fig. 3

Adjusted SVR rates after propensity score matching for TPV/PR and BOC/PR treated patients

Fig. 4

Comparison of the SVR24 rates between pivotal clinical trials and this study after adjusting for confounding

Fig. 5

Comparison of the SVR24 rates between the Irish national registry and other international real world studies