Real-world cure rates for hepatitis C virus treatments that include simeprevir and/or sofosbuvir are comparable to clinical trial results

Table 1 Baseline characteristics of 508 patients who initiated simeprevir- and/or sofosbuvir-based therapy

	Total	SMV/SOF ± RBV	SOF/RBV	SOF/PEG/RBV
		Continuous: median (IQR)/categorical: n (%)
n	508	178	234	96
Age, yr	60 (54-64)	61 (57-65)	60 (54-65)	56 (50-62)
Race, black, n (%)	71 (14)	27 (15)	23 (10)	21 (22)
HCV genotype, n (%)
1	362 (71)	177 (99.4)	102 (44)	83 (87)
2	69 (14)	0 (0)	69 (29)	0 (0)
3	52 (10)	0 (0)	52 (22)	0 (0)
4	25 (5)	1 (0.6)	11 (5)	13 (14)
Gender, female	183 (37)	67 (39)	87 (39)	29 (31)
BMI, kg/m2	27.7 (24.7-30.8)	27.5 (24.5-30.2)	27.9 (2.6-31.0)	27.7 (25.1-31.1)
Diabetes, n (%)	111 (22)	29 (16)	59 (25)	23 (24)
Naïve to treatment, n (%)	204 (40)	51 (29)	114 (49)	39 (41)
PI failure, n (%)	89 (18)	48 (27)	18 (8)	23 (24)
HCV viral load, log U/mL	6.15 (5.61-6.58)	6.28 (5.78-6.74)	6.05 (5.43-6.50)	6.13 (5.63-6.53)
Hemoglobin, g/dL	13.8 (12.6-15.1)	13.9 (12.8-15.1)	13.5 (12.4-14.7)	14.7 (13.3-15.4)
Platelet, × 103/μL	143 (90-195)	146 (94-193)	125 (71-183)	180 (125-209)
ALT, U/L	63 (39-105)	72 (45-119)	59 (37-99)	60 (37-101)
AST, U/L	62 (38-99)	70 (40-113)	63 (38-101)	48 (33-83)
Total Bilirubin, mg/L	0.70 (0.50-1.10)	0.70 (0.50-1.00)	0.8 (0.5-1.5)	0.60 (0.40-0.83)
Albumin, g/dL	4.0 (3.5-4.4)	4.10 (3.70-4.40)	3.8 (3.2-4.3)	4.20 (3.80-4.45)
FIB-4 score	3.54 (1.73-6.72)	3.66 (1.90-5.99)	4.74 (1.91-9.89)	2.09 (1.46-3.85)
FIB-4 ≥ 3.25, n (%)	267 (54)	97 (56)	137 (61)	33 (34)

SMV: Simeprevir; SOF: Sofosbuvir; RBV: Ribavirin; PEG: Pegylated interferon; IQR: Interquartile range; BMI: Body mass index; PI: Protease inhibitor; HCV: Hepatitis C virus; ALT: Alanine transaminase; AST: Aspartate transaminase.

Table 2 Comparison of the baseline characteristics of patients on simeprevir- and/or sofosbuvir-based regimens and patients on telaprevir- or boceprevir-based regimens

	SMV- and/or SOF-containing regimens	TVR- or BOC-containing regimens	P-value
	Continuous: median (IQR)/categorical: n (%)
n	508	223
Age, yr	60 (54-64)	57 (51-61)	< 0.011
Race, black, n (%)	71/508 (14)	41/223 (18)	0.132
Gender, female, n (%)	183/508 (37)	79/223 (35)	0.892
BMI, kg/m2>	27.7 (24.7-30.8)	27.1 (24.5-30.7)	0.651
Diabetes, n (%)	111/508 (22)	48/223 (22)	0.892
Naïve to treatment, n (%)	204/508 (40)	68/223 (31)	0.012
HCV viral load, log IU/mL	6.15 (5.61-6.58)	6.31 (5.89-6.66)	< 0.013
Hemoglobin, g/dL	13.8 (12.6-15.1)	14.3 (13.1-15.3)	< 0.011
Platelet, × 103/μL	143 (90-195)	152 (107-195)	0.193
ALT, U/L	63 (39-105)	67 (44-106)	0.133
AST, U/L	62 (38-99)	62 (39-104)	0.753
Albumin, g/dL	4.0 (3.5-4.4)	4.2 (3.9-45)	< 0.011
FIB-4 score	3.54 (1.73-6.72)	2.65 (1.77-5.60)	0.063
FIB-4 ≥ 3.25, n (%)	267/508 (54)	98/221 (44)	0.032

¹T-test;

²χ²;

³Mann-Whitney. SMV: Simeprevir; SOF: Sofosbuvir; TVR: Telaprevir; BOC: Boceprevir; IQR: Interquartile range; BMI: Body mass index; HCV: Hepatitis C virus; ALT: Alanine transaminase; AST: Aspartate transaminase.

Table 3 SVR12 rates for 508 patients who initiated therapy with simeprevir- and/or sofosbuvir-based treatment regimens, calculated on an intention-to-treat basis, with imputed data on 14 patients

	SVR12 rates
	SVR/total (%)	95%CI, %
All treatments	372/508 (73)	69-77
SMV/SOF ± RBV	153/178 (86)	80-91
“COSMOS-like" cohort	117/130 (90)	83-94
SOF/RBV	144/234 (62)	55-68
Genotype
1	45/102 (44)	34-54
2	57/69 (83)	71-90
3	35/52 (67)	53-79
4	7/11 (64)	32-88
SOF/PEG/RBV	75/96 (78)	68-86

SVR: Sustained virological response; SMV: Simeprevir; SOF: Sofosbuvir; RBV: Ribavirin; PEG: Pegylated interferon.

Table 4 Cost of care and cost-per-sustained virological response by treatment for 508 patients in study

	HCV medications ($)	Adverse Event costs ($)	Lab fees ($)	Provider fees ($)	Total cost of care ($)	1SVR12 rate (%)	Cost-per-SVR ($)
SMV/SOF ± RBV	26379909	65231	89947	154488	26689574	153/178 (86)	174442 (18588)
SOF/RBV genotype	31616725	143770	136353	215584	32112432	144/234 (62)	223003 (77946)
1	15723055	106274	59942	94435	15983705	45/102 (44)	355193 (98493)
2	5736955	32477	37540	61136	5868109	57/69 (83)	102949 (21346)
3	8279942	5019	31914	49381	8366257	35/52 (67)	239036 (48831)
4	1876773		6956	10633	1894362	7/11 (64)	270623 (124)
SOF/PEG/RBV	9275858	80370	48929	82045	9487202	75/96 (78)	126469 (31052)

¹SVR12 rate was calculated with imputations for 14 patients with an EOT response based on the average SVR12 rate for other patients on the same regimen. SMV: Simeprevir; SOF: Sofosbuvir; RBV: Ribavirin; PEG: Pegylated interferon; SVR: Sustained virological response; HCV: Hepatitis C virus.

Table 5 Univariable and multivariable logistic regression analysis of factors associated with SVR12 for 169 patients treated with simeprevir/sofosbuvir ± ribavirin and a confirmed outcome

SMV/SOF ± RBV	Univariable			Multivariable
	OR	95%CI	P value	OR	95%CI	P value
Age, per yr	1.01	0.96-1.06	0.73
Race, black	0.43	0.15-1.45	0.14
Gender, female	1.69	0.61-5.44	0.34
BMI, per kg/m2	0.97	0.87-1.08	0.55
Diabetes, n (%)	0.64	0.21-2.42	0.47
Naïve to treatment	7.96	1.57-145.37	0.04
PI Failure	0.23	0.08-0.61	< 0.01	0.2	0.06-0.56	< 0.01
Ribavirin	0.78	0.29-2.03	0.61
HCV viral load, per log IU/mL	0.61	0.26-1.26	0.22
Hemoglobin, per g/dL	1.17	0.92-1.48	0.18
Platelets, per 103/µL	1	0.99-1.01	0.19
ALT, per U/L	1	0.99-1.01	0.37
AST, per U/L	1	0.99-1.01	0.89
Total bilirubin, per mg/dL	0.56	0.29-1.06	0.06	0.52	0.28-1.02	0.06
Albumin, per g/dL	1.82	0.72-4.45	0.19
FIB-4 ≥ 3.25	0.66	0.22-1.83	0.44

SMV: Simeprevir; SOF: Sofosbuvir; RBV: Ribavirin; OR: Odds ratio; CI: Confidence interval; BMI: Body mass index; PI: Protease inhibitor; HCV: Hepatitis C virus; ALT: Alanine transaminase; AST: Aspartate transaminase.

Table 6 Univariable and multivariable logistic regression analysis of factors associated with SVR12 for 215 patients treated with sofosbuvir/ribavirin and a confirmed outcome

SOF/RBV	Univariable			Multivariable
	OR	95%CI	P value	OR	95%CI	P value
Age, per yr	0.98	0.95-1.01	0.14
Race, black	0.33	0.13-0.80	0.02
Gender, female	1.96	1.08-3.65	0.03
BMI, per kg/m2	0.96	0.90-1.01	0.15
Diabetes	0.95	0.50-1.83	0.87
Naïve to treatment	1.24	0.71-2.19	0.45
PI failure	0.33	0.11-0.89	0.03
HCV viral load, per log IU/mL	0.80	0.56-1.11	0.2
HCV genotype
1	Ref	Ref	Ref	Ref	Ref	Ref
2	7.24	0.57-1.29	< 0.01	4.66	2.06-11.42	< 0.01
3	3.29	1.55-7.37	< 0.01	2.76	1.22-6.59	0.02
4	2.03	0.57-8.21	0.28	1.91	0.51-8.06	0.35
Hemoglobin, per g/dL	1.11	0.95-1.32	0.17
Platelet, per 103/μL	1.01	1.01-1.02	< 0.01
ALT, per U/L	1	0.99-1.00	0.1
AST, per U/L	0.99	0.99-1.00	< 0.01
Total bilirubin, per mg/dL	0.37	0.24-0.55	< 0.01	0.47	0.30-0.69	< 0.01
Albumin, per g/dL	3.15	1.98-5.19	< 0.01
FIB-4 ≥ 3.25	0.23	0.12-0.45	< 0.01

CI: Confidence interval; OR: Odds ratio; BMI: Body mass index; PI: Protease inhibitor; HCV: Hepatitis C virus; ALT: Alanine transaminase; AST: Aspartate transaminase; SOF: Sofosbuvir; RBV: Ribavirin; SVR: Sustained virological response.

Table 7 Univariable and multivariable logistic regression analysis of factors associated with SVR12 for 86 patients treated with sofosbuvir/pegylated interferon/ribavirin and a confirmed outcome

SOF/PEG/RBV	Univariable			Multivariable
	OR	95%CI	P value	OR	95%CI	P value
Age, per yr	0.99	0.94-1.04	0.67
Race, black	0.98	0.30-3.86	0.98
Gender, female	2.31	0.67-10.79	0.22
BMI, per kg/m2	0.95	0.83-1.09	0.42
Diabetes, n (%)	1.15	0.35-4.48	0.83
Naïve to treatment	7.72	1.98-51.36	< 0.01	7.01	1.69-48.27	0.02
PI failure	1.06	0.32-4.16	0.92
HCV viral load, log IU/mL	1.07	0.55-1.92	0.83
HCV genotype
1	Ref	Ref	Ref
4	1.42	0.33-9.83	0.67
Hemoglobin, per g/dL	1309	0.76-1.55	0.64
Platelets, per 103/μL	1.01	0.99-1.02	0.14
ALT, per U/L	0.99	0.98-1.01	0.39
AST, per U/L	0.98	0.96-0.99	< 0.01
Total bilirubin, per mg/dL	0.18	0.04-0.73	0.02
Albumin, per g/dL	3.50	1.21-11.04	0.03
FIB-4 ≥ 3.25	0.16	0.05-0.50	< 0.01	0.18	0.05-0.59	< 0.01

PEG: Pegylated interferon; SOF: Sofosbuvir; RBV: Ribavirin; OR: Odds ratio; CI: Confidence interval; BMI: Body mass index; PI: Protease inhibitor; HCV: Hepatitis C virus; ALT: Alanine transaminase; AST: Aspartate transaminase; SVR: Sustained virological response.

Table 8 Fully adjusted multivariable logistic regression model of factors associated with SVR12 among 169 patients treated with simeprevir/sofosbuvir ± ribavirin and a confirmed outcome

SMV/SOF ± RBV	Univariable			Multivariable
	OR	95%CI	P value	OR	95%CI	P value
Age, per yr	1.01	0.96-1.06	0.73	0.97	0.87-1.06	0.55
Race, black	0.43	0.15-1.45	0.14	0.66	0.11-4.90	0.66
Gender, female	1.69	0.61-5.44	0.34	0.41	0.08-1.94	0.26
BMI, per kg/m2	0.97	0.87-1.08	0.55	1.02	0.88-1.20	0.75
Diabetes, n (%)	0.64	0.21-2.42	0.47
Naïve to treatment	7.96	1.57-145.37	0.04
PI failure	0.23	0.08-0.61	< 0.01	0.12	0.02-0.52	< 0.01
Ribavirin	0.78	0.29-2.03	0.61	0.64	0.09-3.78	0.63
HCV viral load, per log IU/mL	0.61	0.26-1.26	0.22	0.21	0.05-0.70	0.02
Hemoglobin, g/dL	1.17	0.92-1.48	0.18
Platelet, per 103/μL	1	0.99-1.01	0.19	1.01	0.99-1.02	0.35
ALT, per U/L	1	0.99-1.01	0.37	1.01	0.99-1.02	0.41
AST, per U/L	1	0.99-1.01	0.89
Total Bili, per mg/dL	0.56	0.29-1.06	0.06	0.31	0.08-0.86	0.04
Albumin, per g/dL	1.82	0.72-4.45	0.19
FIB-4 ≥ 3.25	0.66	0.22-1.83	0.44	0.89	0.10-6.29	0.92

BMI: Body mass index; PI: Protease inhibitor; HCV: Hepatitis C virus; ALT: Alanine transaminase; AST: Aspartate transaminase; SVM: Simeprevir; SOF: Sofosbuvir; RBV: Ribavirin.