This is an extensive evaluation of Patient-Reported Outcomes (PROs) during and after treatment with 2 pangenotypic regimens for HCV. Our data clearly show that both regimens improve several PRO scores shortly after initiation of treatment. This improvement in PROs persisted throughout treatment and was even more considerable after achieving SVR-12. Moreover, the gains in PROs were not only sustained 12 weeks post-treatment but continued to further improve by Week 24 of follow-up.
Clinical Gastroenterology and Hepatology
April 2018 Volume 16, Issue 4, Pages 567–574.e6
Patient-Reported Outcomes Following Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Velpatasvir, With or Without Voxilaprevir
Young-A HeoEmail authorEmma D. Deeks
Background & Aims
Chronic infection with hepatitis C virus (HCV) has many hepatic and extrahepatic manifestations, measured by patient-reported outcomes (PROs). We measured changes in PROs during HCV treatment with recently developed pangenotypic regimens and from a sustained virologic response 12 weeks after treatment ended (SVR12).
Methods
We collected PRO data from 2 multi-center, blinded, international phase 3 trials of sofosbuvir, velpatasvir, and voxilaprevir, from 748 patients previously treated with direct-acting antivirals for chronic infection with HCV of any genotype (59% HCV genotype 1, 43% with compensated cirrhosis) (POLARIS-1 and POLARIS-4). The combination of sofosbuvir, velpatasvir, and voxilaprevir was given to 445 patients, the combination of sofosbuvir and velpatasvir to 151 patients, and placebo to 152 patients. Patients completed the SF-36, FACIT-F, CLDQ-HCV, and WPAI:SHP questionnaires at baseline, during treatment, and during the follow-up period.
Results
There was no difference in baseline clinical or demographic features or PRO scores among the groups (all P > .05). The group that received the combination of sofosbuvir, velpatasvir, and voxilaprevir had more gastrointestinal symptoms than the groups that received sofosbuvir and velpatasvir or placebo (P = .0001). An SVR12 was achieved by 90.1% of patients who received sofosbuvir and velpatasvir vs 96.9% of patients who received sofosbuvir, velpatasvir, and voxilaprevir (P = .0008). After 12 weeks of treatment, some PRO scores improved in both treatment groups (by 2.5 or by 9.1 points, on a 0–100 scale; P < .05) but not in the placebo group. All increases in PRO scores were sustained or increased after treatment ended (an increase of up to 11.1 points at 12 weeks after treatment and an increase of up to 16.6 points at 24 weeks after treatment ended) (P < .05 for all but 2 PROs). There were no differences in PROs between the sofosbuvir and velpatasvir group vs the sofosbuvir, velpatasvir, and voxilaprevir group (all P > .05). In multivariate analysis, after adjustment for clinical and demographic factors and baseline PRO scores, receiving treatment was associated with higher PROs scores than receiving placebo (beta as high as 5.1) (P < .05).
Conclusions
In an analysis of data from 2 phase 3 clinical trials of patients with chronic HCV infection of any genotype, we found the combination of sofosbuvir, velpatasvir, with or without voxilaprevir, to increase PRO scores compared with placebo. These findings indicate the comprehensive benefit of these regimens during treatment and after SVR.
Chronic infection with hepatitis C virus (HCV) has many hepatic and extrahepatic manifestations, measured by patient-reported outcomes (PROs). We measured changes in PROs during HCV treatment with recently developed pangenotypic regimens and from a sustained virologic response 12 weeks after treatment ended (SVR12).
Methods
We collected PRO data from 2 multi-center, blinded, international phase 3 trials of sofosbuvir, velpatasvir, and voxilaprevir, from 748 patients previously treated with direct-acting antivirals for chronic infection with HCV of any genotype (59% HCV genotype 1, 43% with compensated cirrhosis) (POLARIS-1 and POLARIS-4). The combination of sofosbuvir, velpatasvir, and voxilaprevir was given to 445 patients, the combination of sofosbuvir and velpatasvir to 151 patients, and placebo to 152 patients. Patients completed the SF-36, FACIT-F, CLDQ-HCV, and WPAI:SHP questionnaires at baseline, during treatment, and during the follow-up period.
Results
There was no difference in baseline clinical or demographic features or PRO scores among the groups (all P > .05). The group that received the combination of sofosbuvir, velpatasvir, and voxilaprevir had more gastrointestinal symptoms than the groups that received sofosbuvir and velpatasvir or placebo (P = .0001). An SVR12 was achieved by 90.1% of patients who received sofosbuvir and velpatasvir vs 96.9% of patients who received sofosbuvir, velpatasvir, and voxilaprevir (P = .0008). After 12 weeks of treatment, some PRO scores improved in both treatment groups (by 2.5 or by 9.1 points, on a 0–100 scale; P < .05) but not in the placebo group. All increases in PRO scores were sustained or increased after treatment ended (an increase of up to 11.1 points at 12 weeks after treatment and an increase of up to 16.6 points at 24 weeks after treatment ended) (P < .05 for all but 2 PROs). There were no differences in PROs between the sofosbuvir and velpatasvir group vs the sofosbuvir, velpatasvir, and voxilaprevir group (all P > .05). In multivariate analysis, after adjustment for clinical and demographic factors and baseline PRO scores, receiving treatment was associated with higher PROs scores than receiving placebo (beta as high as 5.1) (P < .05).
Conclusions
In an analysis of data from 2 phase 3 clinical trials of patients with chronic HCV infection of any genotype, we found the combination of sofosbuvir, velpatasvir, with or without voxilaprevir, to increase PRO scores compared with placebo. These findings indicate the comprehensive benefit of these regimens during treatment and after SVR.
Discussion
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This is an extensive evaluation of Patient-Reported Outcomes (PROs) during and after treatment with 2 pangenotypic regimens for HCV. Our data clearly show that both regimens improve several PRO scores shortly after initiation of treatment. This improvement in PROs persisted throughout treatment and was even more considerable after achieving SVR-12. Moreover, the gains in PROs were not only sustained 12 weeks post-treatment but continued to further improve by Week 24 of follow-up.
Download Full-Text
View Online
This is an extensive evaluation of Patient-Reported Outcomes (PROs) during and after treatment with 2 pangenotypic regimens for HCV. Our data clearly show that both regimens improve several PRO scores shortly after initiation of treatment. This improvement in PROs persisted throughout treatment and was even more considerable after achieving SVR-12. Moreover, the gains in PROs were not only sustained 12 weeks post-treatment but continued to further improve by Week 24 of follow-up.
We believe that initial gains in PROs are related to viral suppression that can occur with both regimens. Indeed, no similar improvement was seen in subjects who received placebo in a blinded fashion. In addition, unlike previously studied interferon + ribavirin-containing and interferon-free ribavirin-containing regimens, which resulted in decrements in PROs during treatment and weeks after treatment cessation,18, 22 no treatment-emergent PRO decrements were observed in actively treated patients in this study. Furthermore, presented PRO gains were similar to those reported for other all-oral interferon- and ribavirin-free regimens regardless of their duration.8, 15, 16, 20, 21, 23 This suggests that patients’ experience was not adversely affected by the side effects of the studied regimens and supports excellent tolerability of these regimens for HCV treatment.
In addition to the PRO benefit during treatment, the data clearly show that achieving SVR leads to sustainable gains in PROs, again consistent with previous reports for other DAA-based regimens.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 The magnitudes of post-SVR PRO improvements suggest their clinical relevance because most PROs increased by more than 3%–5% of a PRO range size, which is believed to be the minimal clinically important difference in PROs.38, 39
Furthermore, such improvements are comparable with long-term improvements in PRO scores observed in patients who had cardiac bypass surgery for their coronary artery disease or patients with rheumatoid arthritis after 24 weeks of treatment with methotrexate.40, 41 Accompanied by high efficacy of SOF/VEL ± VOX regimens, these PRO data provide support to the comprehensive benefit (to include clinical, or SVR, and patients’ experience, or PROs) of these new regimens for HCV-infected patients.
Finally, we have confirmed that the presence of cirrhosis, fatigue, and psychiatric comorbidities contributes to impaired PROs in patients with HCV; this is consistent with similar findings from prior studies.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 Although the exact causes of the observed association of location with baseline PROs are unclear, this is also consistent with prior reports on the contribution of cultural and ethnic factors to various PRO measures.42, 43 Nevertheless, the sociodemographic reasons for this difference requires future investigation. Furthermore, our multivariate analysis clearly shows that receiving active treatment with SOF/VEL or SOF/VEL/VOX is independently and similarly associated with improvement of PROs during treatment and in post-treatment follow-up. It is important to note, however, that other major predictors of greater on-treatment and post-treatment PRO gains were factors associated with lower baseline scores, such as history of depression, anxiety, and clinically overt fatigue, suggesting that these conditions, potentially associated with the extrahepatic manifestations of HCV, may also potentially resolve with virologic clearance; further prospectively designed studies are needed to confirm this hypothesis.
The main limitation of this study is the setting where PRO data were collected. Given that the PRO improvements were documented in the clinical trials setting, similar data from real-world clinical practices are needed; this issue applies both to clinical outcomes and PROs. Other limitations include open-label design of POLARIS-4, which might have affected PROs in participants; limited follow-up duration; and the lack of data on other potentially important PRO predictors, such as patients’ education, family status, and other socioeconomic parameters.
In summary, our study assessed the effect of 2 anti-HCV regimens, SOF/VEL and SOF/VEL/VOX, on PRO scores. The data are supportive of the comprehensive benefit of the new all-oral pangenotypic regimens for patients infected with HCV who had failed another DAA-based regimen and might have been left with no treatment options otherwise.
Continue to article: http://www.cghjournal.org/article/S1542-3565(17)31360-5/fulltext
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