Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1

Table 1 Patient demographics and baseline disease characteristics

n (%)	GT1b		GT1a
	DCV + pegIFN/RBV (n = 268)	TVR + pegIFN/RBV (n = 134)	DCV + pegIFN/RBV (n = 134)	TVR + pegIFN/RBV (n = 66)
Age (yr), median (range)	46.0 (18-71)	48.0 (19-69)	49.0 (19-67)	51.5 (28-69)
Male	159 (59.3)	72 (53.7)	98 (73.1)	47 (71.2)
Race
White	243 (90.7)	129 (96.3)	120 (89.6)	63 (95.5)
Black/African American	16 (6.0)	3 (2.2)	11 (8.2)	2 (3.0)
Asian	6 (2.2)	2 (1.5)	1 (0.7)	0
Other	3 (1.1)	0	2 (1.5)	1 (1.5)
HCV-RNA log10 (IU/mL), mean (SD)	6.23 (0.701)	6.23 (0.577)	6.30 (0.637)	6.31 (0.636)
HCV-RNA ≥ 800000 IU/mL	196 (73.1)	97 (72.4)	104 (77.6)	51 (77.3)
IL28B genotype
CC	53 (19.8)	27 (20.1)	42 (31.3)	20 (30.3)
CT	161 (60.1)	86 (64.2)	73 (54.5)	37 (56.1)
TT	53 (19.8)	21 (15.7)	19 (14.2)	9 (13.6)
Not reported	1 (0.4)	0	0	0
Cirrhosis
Present	26 (9.7)	15 (11.2)	16 (11.9)	9 (13.6)

DCV: Daclatasvir; GT: Genotype; HCV: Hepatitis C virus; pegIFN: Peginterferon alfa-2a; RBV: Ribavirin; TVR: Telaprevir.

Table 2 Efficacy endpoints and failures in GT1b-infected patients

Outcome, n/n (%)	DCV + pegIFN/RBV	TVR + pegIFN/RBV
Efficacy
SVR12 (mITT)12	228/268 (85.1)	109/134 (81.3)
SVR12 on or after PT week 123	230/268 (85.8)	110/134 (82.1)
RVR (HCV-RNA undetectable at week 4)14	207/268 (77.2)	106/134 (79.1)
cEVR (HCV-RNA undetectable at week 12)14	243/268 (90.7)	121/134 (90.3)
eRVR (HCV-RNA undetectable at weeks 4 and 12)14	201/268 (75.0)	98/134 (73.1)
EOTR (HCV-RNA undetectable at EOT)	244/268 (91.0)	131/134 (97.8)
SVR2414	226/268 (84.3)	108/134 (80.6)
Failures
Non-SVR12	40/268 (14.9)	25/134 (18.7)
On-treatment failures	21/268 (7.8)	3/134 (2.2)
Virologic breakthrough	11/268 (4.1)	NA5
Treatment futility other than virologic breakthrough	3/268 (1.1)	0
HCV-RNA detectable at EOT	7/268 (2.6)	3/134 (2.2)
Posttreatment relapse6	12/244 (4.9)	20/131 (15.3)
HCV-RNA undetectable at EOT but missing PT week 12 data	7/244 (2.9)	2/131 (1.5)

¹Patients with missing data at posttreatment week 12 were considered failures;

²Difference, 4.3%; 95%CI: -3.3% to 11.9%; noninferior at the 5% significance level (lower bound of the 95%CI was > -12%);

³Patients with missing data at posttreatment week 12 were considered responders if the next available HCV-RNA value was < LLOQ;

⁴Differences and 95%CIs were as follows: RVR, -1.5% (-9.8% to 6.8%); cEVR, 0.6 (-5.5% to 6.6%); eRVR, 2.2% (-6.8% to 11.2%); SVR24, 4.4% (-3.5% to 12.2%);

⁵Not included in TVR futility criteria per prescribing information;

⁶Assessed in patients with undetectable HCV-RNA at EOT. cEVR: Complete early virologic response; DCV: Daclatasvir; EOT: End of treatment; EOTR: End of treatment response; eRVR: Early rapid virologic response; GT: Genotype; HCV: Hepatitis C virus; LLOQ: Lower limit of quantitation; mITT: Modified intent-to-treat; NA: Not applicable; pegIFN: Peginterferon alfa-2a; PT: Posttreatment; RBV: Ribavirin; SVR12: Sustained virologic response (HCV-RNA < LLOQ) at posttreatment week 12; RVR: Rapid virologic response; SVR24: Sustained virologic response at posttreatment week 24; TVR: Telaprevir.

Table 3 Proportion of GT1b-infected patients with SVR12 by subgroups

SVR121, n/n (%)	DCV + pegIFN/RBV(n = 268)	TVR + pegIFN/RBV (n = 134)
Age (yr)
< 65	218/256 (85.2)	103/126 (81.7)
≥ 65	10/12 (83.3)	6/8 (75.0)
Sex
Male	134/159 (84.3)	61/72 (84.7)
Female	94/109 (86.2)	48/62 (77.4)
Race
White	208/243 (85.6)	105/129 (81.4)
Black/African American	11/16 (68.8)	2/3 (66.7)
Asian	6/6 (100.0)	2/2 (100.0)
Other	3/3 (100.0)	0
Baseline HCV-RNA
< 800000 IU/mL	66/72 (91.7)	33/37 (89.2)
≥ 800000 IU/mL	162/196 (82.7)	76/97 (78.4)
Cirrhosis
Absent	208/242 (86.0)	99/119 (83.2)
Present	20/26 (76.9)	10/15 (66.7)
IL28B genotype
CC	51/53 (96.2)	23/27 (85.2)
CT	132/161 (82.0)	69/86 (80.2)
TT	44/53 (83.0)	17/21 (81.0)

¹mITT analysis (patients with missing data at posttreatment week 12 were considered failures). DCV: Daclatasvir; GT: Genotype; HCV: Hepatitis C virus; pegIFN: Peginterferon alfa-2a; RBV: Ribavirin; SVR12: Sustained virologic response (HCV-RNA < LLOQ) at posttreatment week 12; TVR: Telaprevir.

Table 4 Overall on-treatment safety in GT1-infected patients

Event, n (%)	DCV + pegIFN/RBV (n = 402)	TVR + pegIFN/RBV (n = 200)1
Death	1 (0.2)2	1 (0.5)2
SAEs	26 (6.5)2	20 (10.0)2
AEs leading to discontinuation of any study drug	28 (7.0)2	37 (18.5)2
AEs leading to discontinuation of all 3 study drugs	25 (6.2)	25 (12.5)
AEs (grade 1-4) ≥ 20%
Fatigue	140 (34.8)	81 (40.5)
Headache	137 (34.1)	57 (28.5)
Asthenia	109 (27.1)	53 (26.5)
Pruritus	107 (26.6)	75 (37.5)
Anemia	96 (23.9)	99 (49.5)
Rash	93 (23.1)	69 (34.5)
Nausea	88 (21.9)	74 (37.0)
Neutropenia	87 (21.6)	27 (13.5)
Alopecia	86 (21.4)	32 (16.0)
Influenza-like illness	85 (21.1)	38 (19.0)
Dry skin	84 (20.9)	34 (17.0)
Pyrexia	80 (19.9)	42 (21.0)
Grade 3 or 4 emergent laboratory abnormalities
Hemoglobin	26 (6.5)	41 (20.5)
Absolute neutrophil count	104 (25.9)	41 (20.5)
Lymphocytes	67 (16.7)	44 (22.0)
Platelet count	15 (3.7)	8 (4.0)
ALT	3 (0.7)	4 (2.0)
AST	7 (1.7)	1 (0.5)
Total bilirubin	4 (1.0)	6 (3.0)
Serum creatinine increased	1 (0.2)	0

¹n = 198 for grade 3/4 laboratory abnormalities;

²Further information provided in supplementary material. AE: Adverse event; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; DCV: Daclatasvir; GT: Genotype; pegIFN: Peginterferon alfa-2a; RBV: Ribavirin; SAE: Serious adverse event; TVR: Telaprevir.