Adverse events are common during protease inhibitor therapy for HCV-1: real world
experience
Introduction: The protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC) were
PBS-listed in April 2013. Both drugs significantly improve rates of SVR, but are associated
with additional morbidity. Recent data suggest that adverse events (AEs) may be more
common in real world practice than was observed in the registration studies, particularly in
patients with cirrhosis1. The Australian experience in the use of these triple therapy regimens
has not been previously reported. In this study we present the combined experience of adverse
events (AEs) associated with PI therapy at two large treatment centres in Melbourne.
Methods: Treatment experience with TVR or BOC-based regimens at St Vincent’s Hospital
Melbourne and Monash Medical Centre was collected in comprehensive HCV databases,
including baseline patient characteristics, on-treatment virological responses and adverse
events (AEs). Advanced liver fibrosis was defined as a composite of histology (METAVIR
F3-4) and transient elastography (>9.5kPa). We considered the following AEs: on-treatment
anemia (endpoints - haemoglobin (Hb) reduction of >3 g/dL from baseline, Hb <10g/dL,
RBV dose reduction, blood transfusion), clinically significant rash (indicated by need for
topical steroid treatment), treatment discontinuation, need for hospitalization, and death.
Results: 150 patients have started DAA treatment (BOC, n=80 and TVR, n=70). Patients
were older (mean 51yrs), male (69%), and advanced fibrosis was common (50%). 34% had
previously failed pIFN plus RBV therapy. No patient had Child-Pugh B or C cirrhosis.
Baseline characteristics were similar for BOC and TVR-treated patients. At the time of
submission, 64% remained on treatment. Adverse events were common. Comparison of the
rates of anemia, anemia complications and rash are presented in Table 1.
BOC n = 80
TVR n = 70
35 (44%)
23 (33%)
Anemia Hb < 10g/dL
Hb reduction > 3g/dL
62(78%)
41 (59%)
RBV dose reduction
26 (33%)
25 (36%)
Transfusion
13 (16%)
10 (14%)
Topical steroid
16 (20%)
40 (57%)
Rash
Grade 4
0
2 (3%)
Among BOC-treated patients, 10 (13%) patients stopped treatment due to AEs: severe
depression (n=2), refractory insomnia (n=1), and profound lethargy (n=7, only 1 of which
was associated with anemia), 3 patients were hospitalized for anaemia, infection in the setting
of pancytopenia, and nausea and vomiting, respectively. Among TVR-treated patients, 7
(10%) discontinued due to AEs: 1 patient with severe anaemia (nadir Hb 79, 6 blood
transfusions required in total) in the setting of cryoglobulinaemic myeloproliferative
glomerulonephritis; 1 patient with grade 4 rash (DRESS syndrome); 1 cirrhotic patient
developed a first hepatic decompensation event (spontaneous bacterial peritonitis requiring
ICU admission); and 3 patients were hospitalised for symptomatic anaemia (fatigue and chest
pain). 1 patient died from mucormycosis. 1 patient developed skin necrosis at a pIFN
injection site 12 weeks after cessation of TVR and required a prolonged hospitalization .
Conclusion: Treatment with PI-based triple therapy is challenging. Overall the rates of AEs
were similar to those observed in the registration studies. The most common AE was anemia
for both drugs; rash was more common in patients receiving TVR. Severe AEs were unusual.
Careful monitoring of patients is recommended, particularly in the setting of advanced
fibrosis.
1
Hézode C, et al. AASLD 2012