Table 2.
Rates of Virologic Responses among Patients Who Received at Least One Dose of Any Study Medication, According to Cohort and Treatment Group.*
| Characteristic | Nonblack Cohort | Black Cohort | Both Cohorts | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Group 1 (N = 311) | Group 2 (N = 316) | P Value for Group 2 vs. Group 1 | Group 3 (N = 311) | P Value for Group 3 vs. Group 1 | Group 1 (N = 52) | Group 2 (N = 52) | P Value for Group 2 vs. Group 1 | Group 3 (N = 55) | P Value for Group 3 vs. Group 1 | Group 1 (N = 363) | Group 2 (N = 368) | P Value for Group 2 vs. Group 1 | Group 3 (N = 366) | P Value for Group 3 vs. Group 1 | |
| no. of patients/total no. (%) | no. of patients/total no. (%) | no. of patients/total no. (%) | no. of patients/ total no. (%) | no. of patients/total no. (%) | no. of patients/ total no. (%) | ||||||||||
| Response at end of therapy† | 176/311 (57) | 235/316 (74) | <0.001 | 241/311 (77) | <0.001 | 15/52 (29) | 26/52 (50) | 0.04 | 36/55 (65) | <0.001 | 191/363 (53) | 261/368 (71) | <0.001 | 277/366 (76) | <0.001 |
| Rate of relapse‡ | 37/162 (23) | 21/232 (9) | <0.001 | 18/230 (8) | <0.001 | 2/14 (14) | 3/25 (12) | 1.00 | 6/35 (17) | 1.00 | 39/176 (22) | 24/257 (9) | <0.001 | 24/265 (9) | <0.001 |
| Sustained virologic response§ | |||||||||||||||
| All patients who received treatment | 125/311 (40) | 211/316 (67) | <0.001 | 213/311 (68) | <0.001 | 12/52 (23) | 22/52 (42) | 0.04 | 29/55 (53) | 0.004 | 137/363 (38) | 233/368 (63) | <0.001 | 242/366 (66) | <0.001 |
| Modified ITT population | 125/297 (42) | 211/303 (70) | <0.001 | 213/299 (71) | <0.001 | 12/47 (26) | 22/47 (47) | 0.04 | 29/55 (53) | 0.001 | 137/344 (40) | 233/350 (67) | <0.001 | 242/354 (68) | <0.001 |
| HCV RNA level at wk 4 | |||||||||||||||
| Undetectable or decreased by ≥1 log10 IU/ml | 121/234 (52) | 187/228 (82) | <0.001 | 178/218 (82) | <0.001 | 12/26 (46) | 16/24 (67) | 0.17 | 22/36 (61) | 0.30 | 133/260 (51) | 203/252 (81) | <0.001 | 200/254 (79) | <0.001 |
| Decreased by <1 log10 IU/ml | 3/62 (5) | 21/73 (29) | <0.001 | 31/79 (39) | <0.001 | 0/21 | 6/24 (25) | 0.02 | 5/16 (31) | 0.01 | 3/83 (4) | 27/97 (28) | <0.001 | 36/95 (38) | <0.001 |
| HCV RNA detectability at wk 4 | |||||||||||||||
| Undetectable¶ | 27/28 (96) | 16/18 (89) | 0.55 | 18/20 (90) | 0.56 | 2/2 (100) | 1/1 (100) | 0/0 | 29/30 (97) | 17/19 (89) | 0.55 | 18/20 (90) | 0.56 | ||
| Detectable∥ | 97/268 (36) | 192/283 (68) | <0.001 | 191/277 (69) | <0.001 | 10/45 (22) | 21/47 (45) | 0.03 | 27/52 (52) | 0.003 | 107/313 (34) | 213/330 (65) | <0.001 | 218/329 (66) | <0.001 |
| HCV RNA detectability at wk 8 | |||||||||||||||
| Undetectable | 48/56 (86) | 170/190 (89) | 0.47 | 166/182 (91) | 0.31 | 3/4 (75) | 14/18 (78) | 1.00 | 18/22 (82) | 0.57 | 51/60 (85) | 184/208 (88) | 0.50 | 184/204 (90) | 0.25 |
| Detectable∥ | 73/233 (31) | 38/104 (37) | 0.38 | 44/102 (43) | 0.046 | 8/38 (21) | 8/25 (32) | 0.38 | 8/29 (28) | 0.57 | 81/271 (30) | 46/129 (36) | 0.25 | 52/131 (40) | 0.06 |
| HCV RNA detectability wk 8 through wk 24 | |||||||||||||||
| Undetectable | 37/40 (93) | 143/147 (97) | 0.17 | 137/142 (96) | 0.38 | 3/3 (100) | 13/15 (87) | 0.99 | 18/19 (95) | 1.00 | 40/43 (93) | 156/162 (96) | 0.40 | 155/161 (96) | 0.40 |
| Detectable** | 78/118 (66) | 52/70 (74) | 0.26 | 48/65 (74) | 0.32 | 8/13 (62) | 7/12 (58) | 1.00 | 7/8 (88) | 0.36 | 86/131 (66) | 59/82 (72) | 0.37 | 55/73 (75) | 0.16 |
| Baseline Metavir fibrosis score†† | |||||||||||||||
| 0, 1, or 2 | 111/277 (40) | 194/279 (70) | <0.001 | 186/265 (70) | <0.001 | 12/51 (24) | 19/40 (48) | 0.03 | 25/48 (52) | 0.004 | 123/328 (38) | 213/319 (67) | <0.001 | 211/313 (67) | <0.001 |
| 3 or 4 | 9/23 (39) | 13/26 (50) | 0.57 | 18/36 (50) | 0.44 | 0/1 | 1/8 (12) | 1.00 | 4/6 (67) | 0.43 | 9/24 (38) | 14/34 (41) | 1.00 | 22/42 (52) | 0.31 |
Boceprevir was given for 24 weeks in group 2 and for 44 weeks in group 3, irrespective of the rapidity of achievement of an undetectable HCV RNA level. P values were calculated for the rates of sustained virologic response with the use of the Cochran–Mantel–Haenszel chi-square test, with adjustment for prespecified stratification factors; P values for other response data were calculated by means of Fisher’s exact test. ITT denotes intention to treat.
Response at the end of therapy was defined as an undetectable HCV RNA level at the time that the study therapy was discontinued. The end of therapy was the actual (not assigned) end of treatment.
Rate of relapse was defined as the proportion of patients with a detectable HCV RNA level at the end of the follow-up period, as calculated among the patients with an undetectable level at the end of the treatment period who did not have missing follow-up data.
Sustained virologic response was defined as an undetectable HCV RNA level at the end of the follow-up period. The 12-week post-treatment HCV RNA level was used (as specified in the protocol) if the 24-week post-treatment level was not available. A sensitivity analysis was performed on data from only patients with an undetectable HCV RNA level documented at 24 weeks after treatment: the rates of sustained virologic response for groups 1, 2, and 3 in the nonblack cohort were 39%, 66%, and 68%, respectively, and the rates in the black cohort were 21%, 42%, and 51%, respectively.
In the black cohort, the sample was too small to calculate the P value for the comparison between group 2 and group 1.
Detectable HCV RNA was defined as an HCV RNA level above the limit of detection (9.3 IU per milliliter) at the specified week in patients for whom HCV RNA values were available.
HCV RNA detectability at weeks 8 through 24 was ascertained only in patients receiving more than 28 weeks of therapy. Only 22% of patients (82 of 368) in group 2 were assigned a 48-week fixed treatment duration.
The Metavir fibrosis scores were determined on the basis of assessment of liver-biopsy specimens by a single pathologist who was unaware of the assignment to the boceprevir or placebo group. Possible fibrosis scores are as follows: 0 (indicating no fibrosis), 1 (indicating portal fibrosis without septa), 2 (indicating portal fibrosis with few septa), 3 (indicating numerous septa without cirrhosis), and 4 (indicating cirrhosis).