Safety profile of boceprevir and telaprevir in chronic hepatitis C: Real world experience from HCV-TARGET

Abstract

Background & Aims The safety profiles of boceprevir and telaprevir in the treatment of chronic hepatitis C, administered in academic and community centres across the United States, were evaluated. Methods In 90 medical centres, patients with chronic HCV received pegylated interferon, ribavirin, and either telaprevir or boceprevir per local standard of care. Demographic, adverse event, clinical, and virological data were collected during treatment and follow-up. Results A total of 2084 patients (97% HCV genotype 1) received at least one dose of a protease inhibitor. At baseline, 38% of patients had cirrhosis, and 57% had received at least one prior treatment for hepatitis C. Serious adverse events occurred in 12% of patients receiving protease inhibitor therapy. Overall, 66% of patients experienced anaemia, leading to frequent ribavirin dose reductions (42%) and erythropoietin use (37%); 11% received blood transfusion. More than 90% of patients had adverse events that led to a prescription, treatment, or dosage change, and 39% of patients discontinued treatment early, most commonly because of adverse events (18%) or lack of efficacy (16%). Hepatic decompensation events occurred in 3% of all patients. Age, female gender, cirrhosis, HCV genotype 1 subtype, creatinine clearance, platelet levels, albumin levels and haemoglobin levels were independent predictors of anaemia. Five deaths occurred. Overall, 52% of all patients achieved a sustained virologic response. Conclusions In academic and community centres, where chronic hepatitis C patients commonly have advanced liver disease, triple therapy was associated with a high rate of adverse events and involved frequent treatment modifications and adverse event management.

Sustained Virological Response and Hepatitis C-Related Cirrhosis: a World of Opportunities

“…Other real-life cohort studies worldwide have confirmed the abovementioned results [12][13][14][15]. The efficacy of triple antiviral therapy in patients with advanced fibrosis or cirrhosis is higher than that of double antiviral therapy with P-R, but it is still far from being optimal.…”

Health-Related Quality of Life in patients with hepatitis C in double and triple therapy

“…In a study published evaluating the safety of telaprevir in 1782 patients with advanced liver fibrosis, anemia was present in 931 (59%) patients and 157 (10%) patients required blood transfusions (26) . Another study reported that 90% of 2084 patients treated with triple therapy in the US experienced adverse events, requiring some intervention and 39% of patients discontinued therapy prematurely (27) . It is possible that such events have also contributed to the diminished HRQoL observed in this study.…”

Pharmacogenomic Testing in the Era of Patient-Tailored HCV Treatment

“…Indeed, since the triple therapy also involved PegIFN and RBV, some adverse effects induced by those drugs were persistent compared with the previous treatment regimen. However, the addition of NS3/4A protease inhibitor (PI) not only intensified some of the IFN-induced ADRs such as anemia, but also led to novel side effects like skin rashes, gastrointestinal disorders and dysgeusia [18,30]. In November 2013, simeprevir (SMV), as a second generation NS3/4A inhibitor was approved by the FDA, which contrary to prior developed drugs in this class, was more convenient regarding dosing and had fewer ADRs [31,32].…”