We found that in a population of treatment-eligible patients with chronic HCV, a relatively small proportion initiated treatment with pegylated interferon and ribavirin, and far fewer completed the course of therapy, within 12 months of follow-up. Of significant concern was that a substantial proportion of patients with severe liver disease (fibrosis Stages 3 or 4 or clinical cirrhosis) refused therapy or failed to initiate treatment. Of those with severe disease, only 28% completed a course of therapy. Treatment patterns did align with current treatment recommendations (disease severity was positively associated with initiation of treatment). However, this study highlights the persistence of suboptimal treatment initiation and completion patterns particularly in patients with advanced disease. This is also the first study documenting that patient choice predisposition is a strong predictor of treatment initiation, independent of disease severity. We would argue that with currently available therapies, optimization of treatment for hepatitis C requires attention to both the evaluation of patients’ choice predisposition, and the reduction of barriers to treatment initiation.
While there is generally low uptake and completion of therapy in HCV, it is most important to be able to identify patients with severe disease who are at higher risk for failing to initiate treatment. In this study, we found a strong association between patient choice predisposition and initiation of treatment, independent of underlying liver disease severity. This finding may support the practice of measuring choice predisposition (using a previously validated eleven-point numeric rating scale)38
in clinical practice. This simple screening tool could be used to identify patients with severe disease who are at higher risk of not initiating treatment and may benefit from more targeted education strategies or support. We found no significant association between treatment initiation and sociodemographic characteristics including HCV-related quality of life, when controlling for liver disease severity. Ultimately, identifying the specific factors that drive patient preference or choice predisposition may allow for the development of more targeted interventions to increase the number of eligible patients initiating therapy.
Despite the extensive education provided at both sites, one-quarter of patients with severe disease declined treatment even after discussion with their hepatologist. This suggests that patient education alone is insufficient to motivate a significant number of patients with severe disease to accept pegylated interferon and ribavirin for chronic HCV. Further studies will determine whether uptake is higher with triple therapy. Although most of the participants (56%) reported their intent to initiate treatment after seeing their hepatologists, only 55 of 148 (37%) actually initiated treatment within the 12 months. Current guidelines from the NIH, AASLD, and VA recommend treatment for all eligible patients with moderate or severe disease, while individualizing treatment plans for patients with mild disease.1
In our study, only 50% of patients with severe disease initiated treatment, indicating suboptimal treatment initiation rates among patients most in need of treatment.
Our results are consistent with previous studies citing low treatment rates, with only 11.8%–30% of patients chronically infected with HCV undergoing treatment.18
However, in contrast to our approach, these studies included patients that they considered ineligible for treatment such as patients with active substance abuse, psychiatric comorbidities, advanced cirrhosis, normal liver function tests, or an undetectable viral load. These studies also did not stratify by disease severity. In our study we included only patients that we considered eligible for treatment, who underwent intensive education about chronic HCV, its complications and treatment, and had already followed up with a liver specialty clinic. Moreover, many of our study patients had access to the Hepatitis C Resource Center at the VA Connecticut Health System, which is a multidisciplinary team dedicated to treating patients with active psychiatric and substance abuse comorbidities. This method of individualizing care for these patients with relative, not absolute, contraindications to treatment would be expected to improve the ability to capture more individuals as “suitable” candidates for treatment. Despite the abundance of patient support and education, and the exclusion of treatment-ineligible patients from our study, we found that only a minority of patients initiated treatment. These results indicate that there are significant barriers to initiating treatment beyond screening and education.
Reasons for not initiating treatment in our subjects fell into two major categories, system factors and patient-driven factors. System factors included geographic barriers (inability to arrange transportation to appointments or to find a provider within a reasonable distance), financial limitations, and inadequate insurance coverage. Financial concerns were a significant barrier even in the veteran population, where non-service connected veterans have to pay $9 for each prescription and $50 copayment for each specialty clinic visit. The most common patient factors reported by the subjects in this study included that they had missed their appointments, had difficulty arranging sufficient time away from their responsibilities (eg, family, school, work) to commit to treatment, and had continued uncertainty regarding the risk-benefit tradeoffs of currently available therapies. System factors predominated for subjects with severe disease. These results suggest that interventions aimed at reducing geographic and financial barriers may increase the number of patients with severe disease willing to initiate therapy.
In addition to suboptimal treatment initiation rates, treatment completion rates were also low (19% overall at 12 months) among our population within the 12 months of our study. Half of the patients that initiated treatment either discontinued treatment or were lost to follow-up. These discontinuation rates are similar to other cited studies of non-clinical trial patients.20
Our results are also consistent with studies showing poorer treatment response rates in patients with genotype 1, severe liver disease, and age greater than 40 years; characteristics that predominated among subjects in this study who initiated treatment.10
Most of our patients had treatment discontinued by their hepatologist because of drug-related toxicity or lack of viral response. Only six patients self-discontinued treatment, mainly due to inability to tolerate side effects. Factors that were associated with initiation of treatment (namely disease severity and choice predisposition) appeared to have no association with completion of treatment. Similarly, the sole factor correlating with treatment completion (marital status) had no association with treatment initiation. While not examined directly in our study, previous studies have shown the addition of telaprevir or boceprevir to pegylated interferon and ribavirin to be associated with similar or increased rates of adverse events, with discontinuation rates of 7%–21% for triple-therapy regimens.12
These results suggest that success rates with currently available drugs will continue to be limited despite efforts to improve screening for HCV and uptake of therapy. Improving the efficacy and tolerability of medication classes will be most crucial to optimize treatment completion rates.
To the best of our knowledge, this is the first study of its kind evaluating both patient preferences immediately prior to discussion about treatment initiation with the patients’ treating hepatologist, and patient treatment patterns over time. Other strengths include the exclusion of patients that were not eligible for HCV treatment and the stratification of patients based on liver disease severity. There are also important limitations to note. Although we recruited patients from both university and VA-based clinics, the majority were from the VA clinics. Thus, our study participants may not be fully representative of other samples that are community-based. Because our study examined pegylated interferon- and ribavirin-based regimens, generalizability to newer triple therapy regimens may be limited. However, the barriers to treatment initiation elucidated in this paper remain independent of the addition of these new medications. Additionally, triple therapy regimens as they currently stand continue to include both pegylated interferon and ribavirin. Finally, given our sample size, the associations found should be replicated in larger study populations.
Although physician-based guidelines for initiating antiviral treatment for eligible patients with chronic HCV are based strongly on disease severity, individual patient preferences are diverse and varied. Our study highlights the association of both disease severity and patient choice predisposition with initiation of antiviral treatment. Elucidating the specific modifiable patient characteristics that determine choice predisposition at the time of discussion of antiviral treatment will be pivotal to optimizing treatment initiation rates in all patients. This is particularly important in patients with more severe disease who are most likely to benefit from treatment. Our study also highlights the importance of addressing systemic barriers to treatment. This is true even for systems that prioritize access, such as the VA. However, despite efforts to increase initiation rates, the high discontinuation rate in our population underscores the importance of developing newer therapies with more favorable toxicity and efficacy profiles. Improving treatment outcomes for patients with chronic HCV will require concerted efforts to (1) identify patients with severe disease who are reluctant to initiate therapy, (2) improve access for those wishing to initiate therapy, and most importantly, (3) develop newer therapies that both improve efficacy and reduce the burden of adverse events related to treatment.