Table 3.
Adverse Events and Reasons for Discontinuation of Telaprevir Only and of All Study Drugs.*
| Event | Total (N = 540) | Randomly Assigned to T12PR24 (N = 162) | Randomly Assigned to T12PR48 (N = 160) | Nonrandomly Assigned to T12PR48 (N = 118) | Discontinued Treatment before Wk 20 (N = 100) |
|---|---|---|---|---|---|
| number (percent) | |||||
| Any serious adverse event | 49 (9) | 4 (2) | 16 (10) | 7 (6) | 22 (22) |
|
| |||||
| Blood and lymphatic system disorders | 15 (3) | 2 (1) | 5 (3) | 0 | 8 (8) |
|
| |||||
| Anemia | 12 (2) | 1 (1) | 0 | 7 (6) | 4 (4) |
|
| |||||
| Infections and infestations | 10 (2) | 1 (1) | 5 (3) | 3 (3) | 1 (1) |
|
| |||||
| Pneumonia | 3 (1) | 0 | 2 (1) | 1 (1) | 0 |
|
| |||||
| Gastrointestinal disorders | 2 (<1) | 0 | 0 | 0 | 2 (2) |
|
| |||||
| Injury, poisoning, and procedural complications | 3 (1) | 0 | 0 | 0 | 3 (3) |
|
| |||||
| Metabolism and nutrition disorders | 3 (1) | 0 | 3 (2) | 0 | 0 |
|
| |||||
| Dehydration | 2 (<1) | 0 | 2 (1) | 0 | 0 |
|
| |||||
| Respiratory, thoracic, and mediastinal disorders | 3 (1) | 0 | 0 | 0 | 3 (3) |
|
| |||||
| Any adverse event | 537 (99) | 161 (99) | 160 (100) | 117 (99) | 99 (99) |
|
| |||||
| General disorders | 472 (87) | 138 (85) | 139 (87) | 106 (90) | 89 (89) |
|
| |||||
| Fatigue | 369 (68) | 110 (68) | 111 (69) | 81 (69) | 67 (67) |
|
| |||||
| Gastrointestinal disorders | 440 (81) | 132 (81) | 135 (84) | 99 (84) | 74 (74) |
|
| |||||
| Nausea | 253 (47) | 71 (44) | 76 (48) | 61 (52) | 45 (45) |
|
| |||||
| Diarrhea | 164 (30) | 48 (30) | 54 (34) | 38 (32) | 24 (24) |
|
| |||||
| Skin and subcutaneous-tissue disorders | 461 (85) | 142 (88) | 145 (91) | 102 (86) | 72 (72) |
|
| |||||
| Pruritus | 273 (51) | 95 (59) | 83 (52) | 55 (47) | 40 (40) |
|
| |||||
| Rash† | 202 (37) | 60 (37) | 62 (39) | 47 (40) | 33 (33) |
|
| |||||
| Nervous system disorders | 311 (58) | 94 (58) | 90 (56) | 79 (67) | 48 (48) |
|
| |||||
| Headache | 204 (38) | 61 (38) | 57 (36) | 51 (43) | 35 (35) |
|
| |||||
| Psychiatric disorders | 288 (53) | 73 (45) | 95 (59) | 72 (61) | 48 (48) |
|
| |||||
| Insomnia | 182 (34) | 50 (31) | 62 (39) | 44 (37) | 26 (26) |
|
| |||||
| Blood and lymphatic system disorders | 287 (53) | 86 (53) | 89 (56) | 62 (53) | 50 (50) |
|
| |||||
| Anemia‡ | 212 (39) | 68 (42) | 66 (41) | 38 (32) | 40 (40) |
|
| |||||
| Discontinuation of telaprevir only owing to adverse events§ | |||||
|
| |||||
| Total | 65 (12) | 21 (13) | 20 (12) | 13 (11) | 11 (11) |
|
| |||||
| Rash events of any severity† | 40 (7) | 14 (9) | 10 (6) | 9 (8) | 7 (7) |
|
| |||||
| Anemia events of any severity‡ | 13 (2) | 6 (4) | 3 (2) | 2 (2) | 2 (2) |
|
| |||||
| Discontinuation of all study drugs | |||||
|
| |||||
| Total¶ | 181 (34) | 1 (1) | 41 (26) | 39 (33) | 100 (100) |
|
| |||||
| Owing to adverse events | 95 (18) | 1 (1) | 20 (12) | 12 (10)¶ | 62 (62) |
|
| |||||
| Rash events of any severity† | 8 (1) | 0 | 1 (1) | 0 | 7 (7) |
|
| |||||
| Anemia events of any severity‡ | 13 (2) | 0 | 2 (1) | 0 | 11 (11) |
|
| |||||
| Other|| | 50 (9) | 0 | 15 (9) | 9 (8) | 26 (26) |
Serious adverse events listed are those that occurred in at least three patients. Adverse events listed are those that occurred in at least 30% of patients. Both are listed according to preferred term of the Medical Dictionary for Regulatory Activities (version 11.0).
Rash was primarily eczematous and resolved after cessation of therapy. Severe rash was observed in 5% of the study patients. Rash events, as assessed with the use of a group of related terms to identify all dermatologic events, were observed in 63% of patients during the telaprevir treatment phase.
Per the study protocol, anemia was to be managed with modification of the ribavirin dose; the use of therapy involving erythropoietin or other hematopoietic growth factors was prohibited according to the final amended protocol. Severe anemia was observed in 6% of the study patients.
The adverse events listed as the cause of telaprevir discontinuation are those of any grade reported during treatment in at least 1% of patients in at least one of the four study groups.
One patient randomly assigned to the T12PR24 group died after having completed treatment during the extended follow-up phase, 277 days after the last dose of study drug; the death was the result of a fall that led to head trauma and was considered unrelated to telaprevir. One patient nonrandomly assigned to the T12PR48 group had completed telaprevir therapy but discontinued peginterferon–ribavirin therapy owing to an adverse event during the post-telaprevir treatment phase. This patient was considered to have discontinued treatment except in safety analyses, since all three study drugs were not discontinued owing to an adverse event.
Other reasons for discontinuation of all the study drugs included withdrawal of consent, loss to follow-up, noncompliance with the drug regimen or other types of noncompliance, refusal of further treatment, and requirement for medication not permitted in the protocol.