Real-world evaluation of eligibility for HCV therapy

Posted on May 3, 2015

In clinical practices in Italy, between January 2009 and February 2010, only 61% of patients with chronic hepatitis C were considered eligible for peginterferon/ribavirin. Reasons treatment was not indicated included patient’s age or mild disease stage. Italian Hepatologists may consider an IFN-based antiviral treatment not cost-effective in older patients with mild HCV disease.

Italy has the highest prevalence rates of hepatitis C virus (HCV) infection in Europe (3-4.4%), with the highest rates of 12.6-26% in the Southern regions and major islands. Although there are approximately 600 dedicated Hepatology centers in Italy to manage cases of chronic HCV, a recent European study emphasized that Italy has had the most limited access to antiviral therapy for HCV over the last two decades (Deuffic-Burban S et al. Gastroenterology 2012;143:974-985). The high cost of recently developed antiviral agents necessitates careful evaluation of patient’s eligibility for therapy, in order to avoid drop-outs due to poor treatment tolerance and unsatisfactory compliance. However, data concerning the overall management of antiviral treatment in actual clinical practices in Italy are still not available.

Characteristics used to determine eligibility for antiviral therapy in Italy were assessed in a non-interventional, prospective, observational, phase 4, multicenter study, published in the journal Digestive and Liver Disease (Vukotic R et al. Dig Liver Dis. 2015 Feb;47(2):151-156). Study-eligible adult patients (N = 1118) who had a diagnosis of chronic hepatitis C, were serum positive for HCV-RNA, and no had history of previous treatment with Peg-IFN, presented at 45 participating centers from January 2009 to February 2010 (the enrolment frame time). During the study period, standard first-line therapy was offered to all the patients in all participating centers. Assignment of a patient to a particular therapeutic strategy was not decided in advance by the trial protocol but was based on current practice, and the prescription of treatment was independent of the decision to include the patient in the study.

  • 347 (31%) patients were recruited in Northern Italy, 268 (24%) in Central Italy and 503 (45%) in Southern Italy
  • 350 patients (31.3%) were examined for the first time at the referring center when recruited, and the remaining 768 (68.7%) were already being followed for their HCV infection before inclusion
  • Males were 51.6%; the mean age was 55.5 ± 14.5 years. The mean body mass index was 25.2±4.3 kg/m² (near overweight) with no gender differences. The most frequent age category was 60-69 years (23.8%), an elderly population. Genotype 1 was the most frequent genotype (47.3%), as reported in most national epidemiological studies, followed by 2 (23.8%), 3 (13.1%) and others.
  • Most frequent concomitant diseases were psychiatric, vascular and metabolic, including insulin resistance and diabetes mellitus; the latter are known to potentially accelerate the progression of chronic liver disease
  • Cirrhosis appeared to be only present in approximately 12% of the studied population. This finding is relevant in Italy because due to financial limitations the current national and regional guidelines restrict allocation of triple antiviral therapy with first generation direct antiviral agents (DAAs) to patients with advanced fibrosis, although patients with mild disease are more likely to successfully respond to treatment.
  • Referring physicians judged 431 (38.5%) patients to be ineligible to receive antiviral treatment
    • Treatment was considered not indicated in 247 (57.3%) of these patients; in the remaining 184 (42.7%), it was considered contraindicated
    • These decisions were based on older age in 144 (33.4%), the presence of one or more co-morbidities in 139 (32.3%), mild CHC in 77 (17.9%), hepatic dysfunction in 41 (9.5%), active substance abuse in 17 (3.9%) and for other reasons in 9 (2.1%).
    • Older age itself was considered the only reason not to indicate antiviral therapy in 91/144 patients, while in the remaining an additional reason (mild disease, co-morbidities, genotype) of ineligibility accompanying the age was reported. Authors note that this typically real-life finding might well indicate that Italian Hepatologists consider an IFN-based antiviral treatment not cost-effective in older patients with mild HCV disease. In addition, older age is often accompanied by concomitant diseases which make IFN-based antiviral treatment more difficult to tolerate or contraindicated.

Among the 687 patients considered eligible for antiviral treatment, 598 (87.0%) patients agreed with the physician’s decision to be treated. However, 89 of these patients refused the treatment protocol. Reasons for refusal included:

  • No explanation (62.9%), fear of side effects (14.6%), decision to postpone treatment (13.5%), comorbidity (4.5%), planned pregnancy (3.4%), and age (1.1%)

Of the 500 patients who received at least one dose of Peg-IFN/RBV:

  • 263 (52.6%) patients achieved a sustained virological response (SVR), similar to observations in randomized controlled trials
  • 71 (14.2%) patients relapsed
  • 166 (33.2%) were either non-responders (61/166) or the treatment outcome data were not available (105/166)
    • The reasons for missing data in 105 patients: patients lost while on-treatment (33.3%), lost during follow-up (25.7%), withdrew for AEs (19.1%), other administrative or unspecified reasons (21.9%)

Of the 500 patients who received at least one dose of Peg-IFN/RBV, 152 (30.4%) did not complete the entire treatment schedule:

  • Principal reasons for discontinuation were lack of response (28.9%), personal reasons (29.6%), AEs (38.2%), and decompensation (1.3%)

The data from this prospective, observational study should help to define the profile of patients who were considered suitable (or not) for dual antiviral therapy with Peg-IFN/RBV in actual clinical practice. Authors concluded the following: even after sofosbuvir and other second generation DAAs with low toxicity will become available in Italy, these drugs will still be combined with PegIFN (at least in genotype 1 infected patients) to optimize virological outcomes. Thus, because of the previously mentioned challenges and of the increased cost of new antiviral regimens, the issue of eligibility for IFN-based regimens is currently still of great concern, although it is likely that the profile of chronic hepatitis C patients will be completely reassessed once all-oral IFN-free regimens will become available.


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