Telaprevir- and boceprevir-based tritherapies in real practice for F3-F4 pretreated hepatitis C virus patients

Table 1 Demographic and baseline characteristics n (%)

Triple therapy: Peg-IFNα2a + Ribavirin +Protease inhibitor,	125
Telaprevir	90 (72)
Boceprevir	35 (28)
Ribavirin dosage mg/kg, mean (SD)	14.4 (2.1)
Age, yr, mean (SD)	56.2 (9.7)
Gender
Male	81 (64.8)
Female	44 (35.2)
HCV genotype
1a	39 (31.2)
1b	71 (56.8)
Undetermined subtype 1	15 (12)
IL28B genotype (rs12979860)
C/T or T/T	88 (84.6)
Viral load, mean (log10 IU/ mL)	6.3 (0.7)
Prior response to anti-viral therapy
Relapsers	46 (37.1)
Null-responders	78 (62.9)
Liver fibrosis grade
Metavir F3	35 (28)
Metavir F4	90 (72)
Child-Pugh score
A	123 (98.4)
B	1 (0.8)
C	1 (0.8)
Liver stiffness values (kPa)
Mean (SD)	17.5 (10.3)
Median (IQR)	14.3 (10.4-20.6)
Oesophageal varices
None	92 (75.4)
Grade 1	16 (13.1)
Grade 2 or 3	14 (11.5)
Mean hemoglobin level (g/dL, mean (SD)	15.1 (1.6)
Mean platelet count × 103/mm3, mean (SD)	165.69 (64.9)
Mean neutrophil count × 103/mm3, mean (SD)	3.4 (1.2)

Relapsers were defined as patients who had undetectable levels of HCV RNA at the end of prior treatment and subsequently relapsed. Null-responders failed to achieve a decline of at least 2 log HCV RNA IU/mL during peg-INF α2a + ribavirin treatment after a minimum duration of 24 wk. Peg-INF: Pegylated-interferon; HCV: Hepatitis C virus; IQR: Inter-quartile range.

Table 2 Factors associated with sustained virological response n (%)

	No sustained virological responsen = 49	Sustained virological responsen = 73	P valueunivariate analysis	P valuemultivariate analysisOR(95%CI)
Protease inhibitor
Telaprevir	30 (34.1)	58 (65.9)	0.0276	NS1
Boceprevir	19 (55.9)	15 (44.1)
Gender
Male	27 (34.2)	52 (65.8)	0.0675	NS1
Female	22 (51.2)	21 (48.8)
HCV genotype 1 subtype
1a	17 (45.9)	20 (54.1)	0.8051	-
1b	26 (37.1)	44 (62.9)
IL28B genotype, rs12979860, n (%)
C/C	4 (25)	12 (75)	0.4420	-
C/T or T/T	40 (45.5)	48 (54.5)
Response to prior therapy				0.008
Null-responders	40 (52.6)	36 (47.4)	0.0004	1.0
Relapsers	9 (20)	36 (80)		3.9 (1.4-10.6)
Grade of liver fibrosis
Metavir F3	11 (31.4)	24 (68.6)	0.2118	-
Metavir F4	38 (43.7)	49 (56.3)
Liver stiffness value (kPa)
Median, kPa (IQR)	17.3 (11.5-28.8)	13.9 (9.4-19.7)	0.0296	0.001
< 21.3 kPa	21 (30)	49 (70)	0.002	8.2 (2.3-29.5)
≥ 21.3 kPa	14 (66.7)	7 (33.3)		1
Rapid virological response	18 (23.7)	58 (76.3)	≤ 0.0001	≤ 0.001
No rapid virological response	26 (68.4)	12 (31.6)		6.9 (2.6-18.2) 1.0
Decrease of ribavirin dosage	18 (37.5)	30 (62.5)	0.6287	-
No decrease of ribavirin dosage	31 (41.9)	43 (58.1)

Sustained virological response (SVR) was analyzed 24 wk after triple therapy withdrawal for 122 patients. Rapid virological response (RVR) under triple therapy was defined as undetectable HCV RNA levels following 4 wk of antiviral triple therapy (i.e., week 4 in the TPV group and week 8 in the BOC treatment group)1. These factors were initially included in the multivariate model (P value < 0.2 in the univariate analysis) and were not independently associated with SVR in the final multivariate model.

Table 3 Safety profile of triple therapy: Severe adverse events grade 3 or 4 n (%)

	Overall patients(n = 124)	Telaprevir(n = 89)	Boceprevir(n = 35)	P valueunivariateanalysis
Premature discontinuation due to SAE	11 (8)	10 (11.2)	1 (2.9)	0.178
Death	0	0	0	-
Severe adverse events grade 3/4	63 (50.8)	46 (51.7)	17 (48.6)	0.75
Infection	4 (3.2)	3 (3.4)	1 (2.9)	1
Liver decompensation	2 (1.6)	2 (2.2)	0	1
Fatigue	3 (2.4)	3 (3.4)	0	0.558
Skin rash	2 (1.6)	2 (2.2)	0	1
Kidney failure	1 (0.8)	1 (1.1)	0	1
Digestive adverse events	1 (0.8)	1 (1.1)	0	1
Thromboembolic events	1 (0.8)	1 (1.1)	0	1
Anemia	18 (14.5)	16 (18)	2 (5.7)	0.081
Neutropenia	21 (16.8)	14 (15.7)	7 (20)	0.568
Thrombocytopenia	42 (33.6)	32 (36)	10 (28.6)	0.434
Erythropoietin use1	65 (52)	45 (90)	20 (57.1)	0.473
Blood transfusion1	17 (13.6)	15 (16.7)	2 (5.7)	0.149

Only severe adverse events (SAEs) of grade 3 or 4 were reported in the table. SAEs were known for 124 patients.

¹Erythropoietin use and blood transfusions were analyzed among the 125 patients. A single subject might have several severe adverse effects.

Table 4 Factors associated with the occurrence of severe adverse events of grade 3 or 4 n (%)

	Severeadverse eventsn = 63	No severeadverse eventsn = 61	P valueunivariate analysis	P valuemultivariate AnalysisOR (95%CI)
Protease inhibitor
Telaprevir	47 (51.7)	43 (48.3)	0.7548	-
Boceprevir	17 (48.6)	18 (51.4)
Genre				0.037
Male	36 (44.4)	45 (55.6)		1.0
Female	27 (62.8)	16 (37.2)	0.0518	2.4 (1.1-5.6)
Liver fibrosis
Metavir F3	15 (42.9)	20 (57.1)	0.2667	-
MetavirF4	48 (53.9)	41 (46.1)
Platelets
Mean × 10³/mm³ (SD)	143.5 (65.43)	191.1 (54.9)	≤ 0.0001	≤ 0.001
< 150 × 10³/mm³	34 (75.6)	11 (24.4)	0.0001	1.0
≥ 150 × 10³/mm³	27 (37.5)	45 (62.5)		5.3 (2.3-12.4)
Albumin, mean, g/L, (SD)	39.4 (4.9)	42 (54.9)	0.0196	-
Bilirubin, median μM/L, (IQR)	13.1 (9.1-19.1)	10.8 (8-13.5)	0.0359	-

The variables initially included in the logistic regression model were those associated with SAEs in the univariate analysis (P value < 0.20). SAEs: Severe adverse events; IQR: Inter-quartile range.