Response rates to HCV treatment in the real world
Posted on May 1, 2015
Approximately 30 to 40 patients with HCV infection are treated annually with the best evidence-based treatment at the Barwon Health Liver Clinic, a 406-bed tertiary care teaching hospital located in Geelong, Victoria, Australia. Being a single hospital, Barwon Health Liver Clinic has more limited nursing and medical resources compared with those provided in large multinational clinical trials. N. Deborah Friedman and colleagues conducted a retrospective review of Barwon Health patients who underwent HCV treatment from establishment of the clinic in January 2001, through to September 2011. The results of this review were published last year in the Journal of Clinical and Experimental Hepatology (N. Deborah Friedman et al. J Clin Exp Hepatol. 2014;4:214–220).
- Patients are managed by a multidisciplinary team comprising of gastroenterologists, infectious disease physicians, a general practitioner with forensic experience, trained hepatology nurses and a dedicated clinic psychiatrist
- Prior to commencing treatment, patients were required to have minimal alcohol intake, have ceased intravenous drug use and not be pregnant or planning a pregnancy
- The clinic’s psychiatrist also reviewed patients if their psychiatric state was of concern.
Subsidized treatment funded by the Australian Government was made available to patients under the Section 100 guidelines (highly specialized drugs program), with eligibility criteria including age >18 years old, contraceptive use and compensated liver disease.
- Treatment regimens for the majority of patients were a combination of weekly subcutaneous 180 mcg PEG-IFN alfa-2a and daily oral RBV
- HCV genotype 1 patients received 48 weeks of therapy
- HCV genotype 2 and 3 patients received 24 weeks of therapy
Two hundred and eight patients either received or were planned to receive the PEG-IFN and RBV treatment. Of these, 18 patients were excluded due to failure to commence the prescribed therapy or incomplete medical records. For the remaining cohort of 190 patients:
- Mean age of the treatment cohort was 42.8 years, and males accounted for 63.2% of the cohort.
- HCV genotype 3 was most common (93/190, 48.9%), and the predominant mode of acquisition was intravenous drug use (140/190, 73.7%)
- 182 patients (for whom SVR data was available) achieved an SVR (58.8%)
- SVR rates of 46.9% in genotype 1, 68.8% in genotype 2 and 62.4% in genotype 3. These results are similar to those of other real-world trials that have been conducted both nationally and internationally. Results for genotype 1 are similar to those reported in registration clinical trials, however, SVR for genotypes 2 and 3 were lower than those demonstrated in pharmaceutical trials.
Of 177 patients for whom hepatic cirrhosis data was available, 29 (16.4%) had clinical, radiological or histological evidence of cirrhosis. These patients had significantly lower SVR rates (20.7%), which is in keeping with the findings of other studies, showing a significant stepwise decline in SVR with increasing fibrosis stage. Cirrhosis significantly decreased the odds ratio (OR) of SVR (OR 0.16, 95% confidence interval (CI): 0.05, 0.45). The authors note that these findings highlight the importance of early HCV treatment, preempting the development of significant cirrhosis. There was no significant relationship between SVR and diabetes, alcohol abuse or intravenous drug use mode of acquisition, or increasing age.
Side effects to therapy were reported in 81.6% of 190 Barwon Health patients. The most common side effects experienced included general malaise (46.3%), hematological disturbances (42.1%) and psychiatric issues (36.8%). Forty of the 190 patients (21.1%), all male, did not complete their planned treatment course:
- Sixteen (8.4%) ceased treatment early because of side effects. These discontinuation rates are better than those reported in some registration clinical trials, which range from 14 to 21%, and are similar to other cohort studies in clinical practice. The authors suggest that the tolerability of HCV treatment can be similar, if not better, in everyday practice to that seen in highly supported clinical trials.
- Age was not associated with development of side effects.
- Twenty-six patients (13.7%) had their treatment dose reduced, predominantly due to hematological side effects
- Both increasing age (OR 1.09, 95% CI: 1.03, 1.16) and female gender (OR 2.78, 95% CI: 1.03, 7.85) were associated with dose reduction
The authors of this real world study made the following conclusion: “our study reveals that response rates to HCV treatment among real-world patients in a regional Australian hospital liver clinic are as good as those seen in pharmaceutical registration trials. Despite including patients with more varied medical and lifestyle comorbidities, as well as potentially not being able to provide the same levels of support and monitoring during treatment compared to clinical trials, these results remain comparable. These findings suggest that HCV treatment can be offered to a broader range of patients, significantly impacting on overall treatment success.” Authors also noted that treatment practices at Barwon Health Liver Clinic are being altered by the recent introduction of direct-acting antiviral therapies, which will also need to be investigated in this real world setting.