This study was the first report from Turkey including Telaprevir based TDR results. The enhanced therapeutic efficacy with combination of telaprevir and standard therapy has been demonstrated in several randomized multicenter trials in patients with genotype 1 CHC (6, 7). In our country, SVR rates reported between 41.2 - 64.4% with standard HCV treatments (8) and our SVR rates with telaprevir based TDR was higher in this study. Our results were similar to other trials (6, 7). Our clinical experience in treating patients with cirrhosis with telaprevir based TDR was limited. Only one patient with compensated cirrhosis was treated and achieved SVR. In PROVE 3 study, response rates were higher in patients with relapse than nonresponders (6). In our study, SVR rates in relapsers and nonresponders were similar, but this could be due to our small sample size.
A multicenter study reported that SVR rate was significantly higher with 48 weeks than 24 weeks therapy in nonresponders (9). In Turkey, the duration of Telaprevir based TDR is 24 weeks; first 12 weeks all three agents and peginterferon and ribavirin for the remaining 12 weeks. Totally, 48-week treatment is recommended for patients not achieved RVR. For this reason, treatment of our four patients with a positive RNA at fourth week was extended to 48 weeks.
Treatment response is influenced by several factors related to the virus (genotype and viral load) or host (fibrosis, age, gender, body weight, duration of the infection) (4). There was no association between SVR and gender, mean HCV-RNA/ALT levels and fibrosis. However, our small sample size might provide inadequate statistical analysis.
In clinical trials, increased serious cutaneous adverse effects have been reported with Telaprevir based TDR (10). In literature, pruritus, eczematous or cutaneous eruption is observed in 56%; besides, severe cutaneous adverse reactions were reported in 3.7% of patients. Pruritus and rash were found in 65.4% and 26.9% of our patients, respectively. Rash was most often observed within the first 4 - 6 weeks, reported in literature (11). In telaprevir phase III trials, the rate of discontinuation of antiviral drugs due to skin manifestation was low (6). In our study, only one patient presented with generalized rash in the seventh week of treatment and her treatment was stopped. In the management of dermatological adverse effects, education of patient about good skin care practices is important. In case of severe cutaneous reaction, discontinuation is strongly recommended. Cutaneous and systemic symptoms usually improve after discontinuation and support care (6, 7, 11). All of our patients with skin disorders, except one, were able to continue treatment using topical corticosteroid and oral antihistamine therapy.
Telaprevir based TDR appears to increase the frequency and severity of anemia. In ADVANCE and PROVE 1 trials, anemia was more common in the Telaprevir arms than the control; however, anemia was transient and resolved after discontinuation of Telaprevir (12, 13). In our study, anemia was a common adverse effect, but rapidly reversed in all patients when Telaprevir discontinued after 12 weeks.
Blood transfusions and reductions in ribavirin doses not less than 600 mg/gun were applied. We found no association between SVR and anemia or ribavirin dose reduction. ADVANCE and ILLUMINATE trials reported that ribavirin dose reduction did not appear to affect SVR rates (13, 14). Telaprevir was generally well tolerated, but hospitalization during treatment period was required for 10 patients. Patients were hospitalized due to severe or symptomatic anemia, rash or impaired general condition and close follow-up of adverse effects. The hospitalization rate seems higher according to general practice in CHC treatments (15).
Telaprevir has been promising for difficult to treat patients with CHC. In most of these patients, curative results were obtained. Our findings suggested that despite more severe and frequent adverse effects of Telaprevir, successful results can be obtained by close follow-up.
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