Table 5Adverse events reported in dose- or duration-ranging trials of pegylated interferons for chronic hepatitis C infection

Study N Treatment History Intervention Ribavirin daily dose Adverse Events
Abergel 2006
France
203Treatment naïvePeginterferon alfa-2b (1.5 μg/kg)
1.5 μg/kg
1x / week for 48 weeks
800 mg dailyWithdrawals due to AE: 8/101 (7.92%)
Anemia: 9/101 (8.91%)
Depression: 13/101 (12.87%)
Dose reduction: 36/101 (35.64%)
Neutropenia: 10/101 (9.9%)
Thrombocytopenia: 3/101 (2.97%)
Suicide: 2/101 (1.98%)
Hypothyroidism: 9/101 (8.91%)
Peginterferon alfa-2b (0.75 μg/kg)
0.75 μg/kg
1x / week for 48 weeks
800 mg dailyWithdrawals due to AE: 4/102 (3.92%)
Anemia: 5/102 (4.9%)
Depression: 15/102 (14.71%)
Dose reduction: 13/102 (12.75%)
Neutropenia: 4/102 (3.92%)
Thrombocytopenia: 0/102 (0%)
Suicide: 0/102 (0%)
Hypothyroidism: 1/102 (0.98%)
Berg 2006
Germany
455Treatment naïvePeginterferon alfa-2a (48 weeks)
180 μg
1× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 21/230 (9.13%)
Dose reduction: 76/230 (33.04%)
Serious AEs: 36/230 (15.65%)
Peginterferon alfa-2a (72 weeks)
180 μg
1× / weeks for 72 weeks
800 mg dailyWithdrawals due to AE: 26/225 (11.56%)
Dose reduction: 82/225 (36.44%)
Serious AEs: 25/225 (11.11%)
Brandao 2006
Brazil
117Treatment naïvePeginterferon alfa-2a (genotype 1, 24 weeks)
180 μg
1x / week for 24 weeks
800 mg dailyWithdrawals due to AE: 2/32 (6.25%)
Deaths: 0/32 (0%)
Depression: 5/32 (15.62%)
Dose reduction: 3/32 (9.38%)
Flu-like symptoms: 8/32 (25%)
Neutropenia: 8/32 (25%)
Thrombocytopenia: 3/32 (9.38%)
Peginterferon alfa-2a (genotype 1, 48 weeks)
180 μg
1x / week for 48 weeks
800 mg dailyWithdrawals due to AE: 0/31 (0%)
Deaths: 0/31 (0%)
Depression: 5/31 (16.13%)
Dose reduction: 9/31 (29.03%)
Flu-like symptoms: 10/31 (32.26%)
Neutropenia: 14/31 (45.16%)
Thrombocytopenia: 7/31 (22.58%)
Peginterferon alfa-2a (genotype non-1, 24 weeks)
180 μg
1x / week for 24 weeks
800 mg dailyWithdrawals due to AE: 2/54 (3.7%)
Deaths: 0/54 (0%)
Depression: 5/54 (9.26%)
Dose reduction: 8/54 (14.81%)
Flu-like symptoms: 29/54 (53.7%)
Neutropenia: 23/54 (42.59%)
Thrombocytopenia: 14/54 (25.93%)
Buti 2002
Israel and Spain
55Treatment naïvePeginterferon alfa-2b (high dose)
1.0 μg/kg
1x / week for 48 weeks
800 mg dailyWithdrawals due to AE: 4/28 (14.29%)
Dose reduction: 1/28 (3.57%)
Peginterferon alfa-2b (low dose)
0.5 μg/kg
1x / week for 48 weeks
800 mg dailyWithdrawals due to AE: 2/27 (7.41%)
Dose reduction: 1/27 (3.7%)
El-Zayadi 2005
Egypt
180Treatment naïvePeginterferon alfa-2b (48 weeks)
100 μg
1x / week for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 2/40 (5%)
Flu-like symptoms: 28/40 (70%)
cytopenia (neutropenia and thrombocytopenia): 12/40 (30%)
psychological disorders: 5/40 (12.5%)
Peginterferon alpha-2b (24 weeks)
100 ug
1x / week for 24 weeks
1000–1200 mg dailyWithdrawals due to AE: 2/70 (2.86%)
Flu-like symptoms: 51/70 (72.86%)
cytopenia (neutropenia and thrombocytopenia): 21/70 (30%)
psychological disorders: 6/70 (8.57%)
Interferon alpha-2b
3 million unit daily for 24 weeks
1000–1200 mg daily-1x/weekWithdrawals due to AE: 2/70 (2.86%)
Flu-like symptoms: 50/70 (71.43%)
cytopenia (neutropenia and thrombocytopenia): 18/70 (25.71%)
psychological disorders: 4/70 (5.71%)
Glue 2000
France
72Treatment naïvePeginterferon alfa-2b (0.35 + RBV)
0.35 μg/kg
1x / week for 24 weeks
800–1200 mg daily
Peginterferon alfa-2b (0.35 alone)
0.35 μg/kg
1x / week for 24 weeks
Peginterferon alfa-2b (0.7 + RBV)
0.7 μg/kg
1x / week for 24 weeks
800–1200 mg daily
Peginterferon alfa-2b (0.7 alone)
0.7 μg/kg
1x / week for 24 weeks
Peginterferon alfa-2b (1.4 + RBV)
1.4 μg/kg
1x / week for 24 weeks
800–1200 mg daily
Peginterferon alfa-2b (1.4 alone)
1.4 μg/kg
1x / week for 24 weeks
Peginterferon alfa-2b (0.7 alone)
Peginterferon alfa-2b (1.4 + RBV)
Peginterferon alfa-2b (1.4 alone)
Hadziyannis 20041284Treatment naïvePeginterferon alfa-2a (24 weeks, low dose RBV)
180 μg
1x / week for 24 weeks
800 mg dailyWithdrawals due to AE: 10/207 (4.83%)
Deaths: 0/207 (0%)
Depression: 43/207 (20.77%)
Dose reduction: 63/207 (30.43%)
Peginterferon alfa-2a (24 weeks, standard RBV)
180 μg
1x / week for 24 weeks
1000–1200 mg dailyWithdrawals due to AE: 13/280 (4.64%)
Deaths: 1/280 (0.36%)
Depression: 42/280 (15%)
Dose reduction: 73/280 (26.07%)
Peginterferon alfa-2a (48 weeks, low dose RBV)
180 μg
1x / week for 48 weeks
800 mg dailyWithdrawals due to AE: 59/361 (16.34%)
Deaths: 1/361 (0.28%)
Depression: 79/361 (21.88%)
Dose reduction: 120/361 (33.24%)
Peginterferon alfa-2a (48 weeks, standard RBV)
180 μg
1x / week for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 67/444 (15.09%)
Deaths: 2/436 (0.46%)
Depression: 104/436 (23.85%)
Dose reduction: 159/436 (36.47%)
Helbling 2006
Switzerland
124Not reportedPeginterferon alfa-2a(standard RBV)
180 μg
1x / week for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 15/64 (23.44%)
Deaths: 0/64 (0%)
Dose reduction: 50/64 (78.12%)
Psychiatric AEs: 1/64 (1.56%)
Peginterferon alfa-2a (low RBV)
180 μg
1x / week for 48 weeks
600–800 mg dailyWithdrawals due to AE: 16/60 (26.67%)
Deaths: 2/60 (3.33%)
Dose reduction: 34/60 (56.67%)
Psychiatric AEs: 4/60 (6.67%)
Jacobson 2005
US
321See commentPeginterferon alfa-2b (higher dose)
1.5 μg/kg
1x / week for 48 weeks
800 mg dailyWithdrawals due to AE: 21/160 (13.12%)
Seroius AEs: 13/160 (8.12%)
Peginterferon alfa-2b (lower dose)
1.0 μg/kg
1x / week for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 18/161 (11.18%)
Serious AEs: 18/161 (11.18%)
Kamal (B) 2005
Egypt
Peginterferon alfa-2b (24 weeks)
1.5 μg/kg
1x / week for 24 weeks
10.6 mg/kg dailyWithdrawals due to AE: 1/95 (1.05%)
Depression: 3/95 (3.16%)
Dose reduction: 5/95 (5.26%)
Flu-like symptoms: 53/95 (55.79%)
Peginterferon alfa-2b (24 weeks)
1.5 μg/kg
1x / week for 24 weeks
10.6 mg/kg dailyWithdrawals due to AE: 1/95 (1.05%)
Depression: 3/95 (3.16%)
Depression: 3/95 (3.16%)
Dose reduction: 5/95 (5.26%)
Flu-like symptoms: 53/95 (55.79%)
Peginterferon alfa-2b (36 weeks)
1.5 μ
1x / week for 36 weeks
10.6 mg/kg dailyWithdrawals due to AE: 2/96 (2.08%)
Depression: 3/96 (3.12%)
Dose reduction: 11/96 (11.46%)
Flu-like symptoms: 58/96 (60.42%)
Peginterferon alfa-2b (36 weeks)
1.5 μ
1x / week for 36 weeks
10.6 mg/kg dailyWithdrawals due to AE: 2/96 (2.08%)
Depression: 3/96 (3.12%)
Dose reduction: 11/96 (11.46%)
Flu-like symptoms: 58/96 (60.42%)
Peginterferon alfa-2b (48 weeks)
1.5 μ
1x / week for 48 weeks
10.6 mg/kg dailyWithdrawals due to AE: 4/96 (4.17%)
Depression: 9/96 (9.38%)
Dose reduction: 12/96 (12.5%)
Flu-like symptoms: 59/96 (61.46%)
Peginterferon alfa-2b (48 weeks)
1.5 μ
1x / week for 48 weeks
10.6 mg/kg DailyWithdrawals due to AE: 4/96 (4.17%)
Depression: 9/96 (9.38%)
Dose reduction: 12/96 (12.5%)
Flu-like symptoms: 59/96 (61.46%)
Lodato 2005
Italy
6540% naïve, 33.8% Non-responders, 26.2% relapsersPeginterferon alfa-2b(1x/week)
1.5 μg/kg
1x / week for 24–48 weeks
10.6 mg/kg dailyAnemia: 2/22 (9.09%)
Depression: 4/22 (18.18%)
Flu-like symptoms: 15/22 (68.18%)
Peginterferon alfa-2b(2x/week)
1.5 μg/kg
2x / week for 24–48 weeks
10.6 mg/kg dailyAnemia: 2/43 (4.65%)
Depression: 8/43 (18.6%)
Flu-like symptoms: 25/43 (58.14%)
Mangia (B) 2005
Italy
283Treatment naïvePeginterferon alfa-2b(standard duration)
1.0 μg/kg
1x / week for 24 weeks
1000–1200 mg dailyWithdrawals due to AE: 8/70 (11.43%)
Peginterferon alfa-2b(variable duration)
1.0 μg/kg
1× / week for 12 or 24 weeks
1000–1200 mg dailyWithdrawals due to AE: 1/213 (0.47%)
Mathew 2006
US
15263% nonresponder, 30% relapser, 7% unavailablePeginterferon alfa-2b (high dose)
1.5 μg/kg
1× / week for 48 weeks
1000–1200 mg daily
Peginterferon alfa-2b (low dose)
0.5 μg/kg
1× / week for 48 weeks
1000–1200 mg daily
Meyer-Wyss 2006
Switzerland
219Treatment naïvePeginterferon alfa-2b (1.0μg/kg)
1.0 μg/kg
1× / week for 24–48 weeks
800 mg dailyWithdrawals due to AE: 14/115 (12.17%)
Anemia: 3/115 (2.61%)
Deaths: 1/115 (0.87%)
Dose reduction: 48/115 (42.48%)
Thrombocytopenia: 3/115 (2.61%)
Peginterferon alfa-2b (1.5μg/kg)
1.5 μg/kg
1× / week for 24–48 weeks
800 mg dailyWithdrawals due to AE: 28/112 (25%)
Anemia: 4/112 (3.57%)
Deaths: 0/112 (0%)
Dose reduction: 63/112 (59.43%)
Thrombocytopenia: 5/112 (4.46%)
Sanchez-Tapias 2006
Spain
326Treatment naïvePeginterferon alfa-2a (48 weeks)
180 μg
1× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 14/165 (8.48%)
Anemia: 30/165 (18.18%)
Depression: 19/165 (11.52%)
Dose reduction: 41/165 (24.85%)
Flu-like symptoms: 39/165 (23.64%)
Neutropenia: 40/165 (24.24%)
Thrombocytopenia: 22/165 (13.33%)
Peginterferon alfa-2a (72 weeks)
180 μg
1× / week for 72 weeks
800 mg dailyWithdrawals due to AE: 19/161 (11.8%)
Anemia: 34/161 (21.12%)
Depression: 31/161 (19.25%)
Dose reduction: 49/161 (30.43%)
Flu-like symptoms: 28/161 (17.39%)
Neutropenia: 41/161 (25.47%)
Thrombocytopenia: 14/161 (8.7%)
Von Wagner 2005
Germany
153Treatment naïvePeginterferon alfa-2a (16 weeks)
180 μg
1× / week for 16 weeks
800–1200 mg dailyWithdrawals due to AE: 0/71 (0%)
Depression: 8/71 (11.27%)
Dose reduction: 5/71 (7.04%)
Flu-like symptoms: 37/71 (52.11%)
Peginterferon alfa-2a (24 weeks)
180 μg
1× / week for 24 weeks
800–1200 mg dailyWithdrawals due to AE: 1/71 (1.41%)
Depression: 10/71 (14.08%)
Dose reduction: 13/71 (18.31%)
Flu-like symptoms: 33/71 (46.48%)
Yu 2006
Taiwan
60Treatment naïvePeginterferon alfa-2b (24 weeks)
80–100 μg
1× / week for 24 weeks
1000–1200 mg dailyWithdrawals due to AE: 1/45 (2.22%)
Anemia: 20/45 (44.44%)
Dose reduction: 7/45 (15.56%)
Thrombocytopenia: 20/45 (44.44%)
Anxiety/depression: 19/45 (42.22%)
Peginterferon alfa-2b (48 weeks)
80–100 μg
1× / week for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 2/15 (13.33%)
Anemia: 8/15 (53.33%)
Dose reduction: 3/15 (20%)
Thrombocytopenia: 4/15 (26.67%)
Anxiety/depression: 8/15 (53.33%)
Zeuzem (A) 2004
Multiple (Australia, Eur, NZ, North and South Am)
PEGASYS Study NR16071
491Treatment naïvePeginterferon alfa-2a (24 weeks)
180 μg
1× / week for 24 weeks
800 mg dailyWithdrawals due to AE: 15/212 (7.08%)
Deaths: 0/212 (0%)
Dose reduction: 23/212 (10.85%)
Peginterferon alfa-2a (48 weeks)
180 μg
1× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 38/210 (18.1%)
Deaths: 0/210 (0%)
Dose reduction: 40/210 (19.05%)
No treatment control
for 72 weeks
Deaths: 1/69 (1.45%)
Zeuzem (B) 2005Treatment naïvePeginterferon alfa-2a(individualized treatment)
See comment
Anemia: 29/136 (21.32%)
Depression: 4/136 (2.94%)
Dose reduction: 69/136 (50.74%)
Neutropenia: 36/136 (26.47%)
Thrombocytopenia: 4/136 (2.94%)
Peginterferon alfa-2a(standard treatment)
180 μg
1× / week for 48 weeks
1000–1200 mg dailyAnemia: 31/134 (23.13%)
Depression: 5/134 (3.73%)
Dose reduction: 79/134 (58.96%)
Neutropenia: 46/134 (34.33%)
Thrombocytopenia: 7/134 (5.22%)

From: Evidence Tables

Cover of Drug Class Review: Pegylated Interferons for Chronic Hepatitis C Infection
Drug Class Review: Pegylated Interferons for Chronic Hepatitis C Infection: Final Report [Internet].
Chou R, Carson S, Chan BKS, et al.
Portland (OR): Oregon Health & Science University; 2007 May.
Copyright © 2007, Oregon Health & Science University, Portland, Oregon.

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