Real-world data and the results from clinical studies are complementary to each other, both provide valuable information in routine clinical practice. The result of this nation-wide, large-scaled study indicates that GLE/PIB is an effective and well-tolerated pangenotypic DAA for Taiwanese patients with CHC infection irrespective of host or viral diversities in the real-world setting.
The characteristics of this patient cohort were generally representative, as the majority of the 3,144 patients were non-cirrhotic (85.1%) and had not undergone other HCV treatment prior to GLE/PIB (92.0%). In accordance with the TFDA-approved label at the time of enrollment, 2,601 (82.7%) of the patients received 8-week treatment regimen. Similar to the previous real-world reports of GLE/PIB, a large part (56.8%) of the current cohort had GT2 infection, in contrast to the overall genotype distribution in Taiwan, which was dominant by GT1. [13, 14] The preponderance of GT2 CHC in GLE/PIB reports reflected the evolution of DAAs, that the treatments of GT1 CHC were licensed earlier than the treatments of other genotypes. [14]
The overall SVR12 rate of 98.9% was comparable with the registrational phase II and III clinical studies [10, 11] and previously published real-world reports. [13, 14, 15, 17] Even when stratified according to cirrhosis status and treatment experience, GLE/PIB demonstrated a similarly high SVR12 rate of 98.5% in the more difficult-to-treat patients who were cirrhotic and had exposed to previous HCV treatment.
In addition, this study reinforced the effectiveness of GLE/PIB in several subpopulations of interest, including patients with HIV or HBV dual infections or with comorbidities such as HCC or CKD. The favorable treatment outcome in CHC patients dually infected with HIV has been previously proven in clinical trials and real-world reports. [10, 13] Unlikely most western countries, both HBV and HCV are endemic in Taiwan [18]. However, the treatment efficacy of GLE/PIB in patients with HBV/HCV dual infection has rarely been validated on a large population basis [13, 19]. In the present cohort, the SVR12 rate of the 248 patients (7.9%) with HBV/HCV dual infection was equally high (98.8%) as in the HCV mono-infected patients (98.9%).
It has been previously reported that patients with active HCC are prone to encounter DAA treatment failure[15, 20], yet the information is scarce with patients who received GLE/PIB. Ninety patients (2.9%) of the present cohort had documented active HCC, and the SVR12 rate of 97.8% was comparable to the patients without a history of HCC (98.9%) or with inactive HCC (100%). As for the 830 patients (26.4%) with renal impairment, the high SVR12 rate of 99.5% was also in line with the previous observations of GLE/PIB. [13, 17, 21] The results of the univariate and subsequent multivariate logistic regression analyses in this study also indicated that the comorbidities of HCC or CKD were not associated with the efficacy outcome of GLE/PIB.
It is important to report the potential factors associated with a lower SVR12 rate. In contrast to the data reported in registration trials [10], lower SVR rates were observed to be associated with males, high baseline HCV RNA levels, HCV GT3 and intravenous drug abuse in the current study. Other large-scaled real-world reports and post marketing observational studies for GLE/PIB have reported conflicting results of the predicting factors including the male gender [22, 23], HCV viral load at baseline [23, 24], GT3 [24, 25] and people who use drugs. [22, 25] It is worth noting that the SVR12 rates remained high (> 95%) for all subgroups analyzed, excepting a numerically lower SVR12 rate of 90.2% for PWID, but it might have been affected by the small number of patients (41, 1.3%).
The phase 3 EXPEDITION-8 trial reported that for the treatment-naïve patients with compensated cirrhosis, 8 weeks of GLE/PIB achieved a high SVR12 rate of 99.7%. [8] Based on this trial, an 8-week GLE/PIB regimen for treatment of cirrhotic patients who received no prior HCV treatment was approved by TFDA in April 2020. It is hoped that reducing treatment duration may help to address remaining gaps in the cascade of care of HCV [4], yet there have only been very limited real-world studies of the effect of the 8-week GLE/PIB regimen on the treatment-naïve patients with compensated cirrhosis [23, 26, 27]. The present study demonstrated that 8 weeks of GLE/PIB achieved a high SVR12 rate (98.2%) in 110 treatment-naïve Taiwanese patients with compensated cirrhosis, supporting the results of EXPEDITION-8. [8]
No specific safety issues were observed from GLE/PIB initiation to the SVR12 survey visit, and the common adverse events were similar to what had been reported in clinical studies [11] or real-world publications. [17, 27]
Compared with the 12-week regimen, 8-week GLE/PIB was associated with a reduction in healthcare resource utilization (5.94 visits vs. 6.90 visits), determined by the number of clinic visits. In consistence with previous reports, the shorter, 8-week treatment with GLE/PIB can reduce healthcare resource use, which may further reduce the health and cost burden of the disease. [28]
Real-world observational studies such as this have inherent limitations. Firstly, the treatment outcomes for certain populations may be inconclusive due to limited patient numbers, such as patients who injected drugs, with HCV GT 4 or 5 infection, or receiving 16-week regimen. Secondly, for the treatment naïve patients with compensated cirrhosis, the 8-week treatment emerged only very recently, and thus only a small portion of such patients were treated for the shorter course. Lastly, the information of drug abuse and data of adverse events were subject to reporting biases, and the causal relationships between the AEs and the treatment could not be fully established.
In conclusion, the result of this study demonstrated that based on the first and largest real-world, nation-wide registry in Taiwan, GLE/PIB was highly effective and safe in treating CHC patients across viral genotypes and special subgroups including treatment-experienced or cirrhotic patients. This study also adds to the growing body of evidence supporting that the shorter, 8-week GLE/PIB regimen may be an effective and cost-saving pangenotypic treatment option for the majority of patients with CHC infection.