Table 6Adverse events in uncontrolled and observational studies of pegylated interferons for chronic hepatitis C infection

Author, year Study design N PEG-IFN Dose Ribavirin daily dose; other drugs Population Duration of treatment Duration of followup Withdrawals due to AEs Other main adverse events
Study of both peginterferon alfa-2a and alfa-2b
DeLuca, 2004Before-after36alfa-2a or alfa-2balfa-2a: 180 μg/week, alfa-2b: 1.5 μg/kg/week>=11mg/kgHIV infection24 weeksup to 72 weeks42% discontinued treatment, occurred at median of 27 weeks (range 3–42 weeks).
Type of PEG-IFN was not associated with discontinuation.
None reported
Studies of peginterferon alfa-2a
Gallegos-Orozco, 2005Before-after18alfa-2a1.5 μg/kg
1x/week for 4 weeks, then 0.5 μg/week
1000–1200 mg (weight-based)Chronic HCV48 weeks24 weeks post-treatment1 treatment discontinuation due to thyrotoxicosis.Dose reduction of PEG-IFN in 1 patient due to neutropenia.
Gheorghe, 2005Before-after174alfa-2a180 μg
1000–1200 mg (weight-based)75.3% treatment naïve, 14.9% relapsers, 9.8% non-responders48 weeks24 weeks post-treatmentDefinitive discontinuation in 5.74%. Causes of treatment discontinuation: severe hematological abnormalities, severe and protracted skin rash, resistance to therapy, personal reasons, and 1 case of acute cytomegalic virus hepatitis.Specific AEs: weight loss 69.9%, fatigue 56.3%, arthralgia 54.6%, pyrexia/chills 52.3%, myalgia 50.6%, irritability 50.4%, decreased appetite 43.5%, prutitis 40.5%, indomnia 38.2%, dry cough 35.1%, depression 33.6%, dry mouth 33.6%, headache 32.87%, alopecia 32.1%, inflammation reaction at injection site 31.6%, skin rash/dermatitis 25.2%, abdominal pain 23.7%, visual disturbances 17.6%, impaired concentration/memory 16.0%, nausea/vomiting 14.9%, epistaxis 13.8%, diarrhea 13.7%, stomatitis 13.0%, taste disturbances 13.0%, infectious complications 8.7%.
Mean weight loss index 0.95 +/− 1.11 kg
Temporary discontinuation of therapy in 2.15% 9.2% required temporary PEG-IFN dose reduction due to neutropenia and thrombocytopenia. Severe anemia requiring blood transfusion occurred in 1.1%, moderate anemia (8–10 g/dl) in 20.1%. 2 severe life-threatening cases of infectious complications (left deltoid necrotizing faciitis, bilateral orchiepididimitis).
Jeffers, 2004Before-after106alfa-2a180 μg
1000–1200 mg (weight-based)Blacks (n=78) and whites (n=28)48 weeks72 weeksNot reportedIncidence rates for AEs higher among whites than blacks, with injection site erythema, vomiting, alopecia, dry skin, and sinusitis having a threefold geater frequency in whites than blacks. One death in a black patient (MI, 180 days after last dose of medication, not considered drug-related).
Specific AEs, (blacks vs whites):
fatigue 60% vs 71%, headache 54% vs 82%, rigors 35% vs 32%, insomnia 27% vs 50%, rash 26% vs 18%, nausea 23% vs 54%, arthralgia 23% vs 21%, myalgia 22% vs 32%, pyrexia 19% vs 25%, anorexia 19% vs 11%, pain 18% vs 21%, pruritis 18% vs 21%, back pain 18% vs 18%, depression 17% vs 29%, influenza-like illness 17% vs 7%, cough 15% vs 11%, dizziness (including vertigo) 13% vs 29%, dyspnea 12% vs 25%, abdominal pain (upper) 12% vs 21%, diarrhea 12% vs 21%, irritability 10% vs 29%, pharyngeal pain 10% vs 21%, alopecia 6% vs 32%, dry mouth 6% vs 18%, injection-site erythema 5% vs 29%, dry skin 4% vs 25%, vomiting 4% vs 21%, sinusitis 3% vs 18%.
Juarez-Navarro, 2005Before-after209alfa-2a180 μg/week800 mg for genotype non-1, 1000 1200 mg in genotype 1excluding those with existing neutropenia and cirrhosis24–48 weeks, depending on genotype4 weeks after completion of therapyNot reportedMeasured infections and neutropenia:
54.5% did not develop neutropenia; 45.5% had neutrophil count <1500 cells/μl; 96.8% 750–1500 cells/μl; 3.2% 500–750 cells/μl; and none <500 cells/μl.
Infection rates were 17%, 33.3%, and 0% for 750–1499; 500–749, and <500 cells/cells/μl; respectively
Lee, 2006Before-after508alfa-2a180 μg/weekno RBV or 800 mg34.3% cirrhotic24 or 48 weeks72 weeks32% of non-cirrhotic and 40% of cirrhotic patients prematurely discontinued treatment.
AEs accounted for discontinuation in <=8% of patients in the combination therapy groups.
Incidence of AEs was similar in cirrhotic and non-cirrhotic patients and across treatment arms.
Overall AEs: 44.7%, Serious AEs: 4.7%, non-serious laboratory abnormalities 30.7%, neutropenia (grade 3): 15.4%, neutropenia (grade 4): 2.2%, neutropenia (not graded): 2.6%, thrombocytopenia (grade 3): 2.2%, thrombocytopenia (not graded): 2.2%, anemia (<10 g/dL): 9.1%, anemia (>=10 g/dL): 2.2%, ALT elevation: 2.0%
Lindahl, 2005Before-after10alfa-2a180 μg/weekmean 2540 mg (range 1600–3600 mg); erythropoiet in 9000–30,000 IU/week.Viral load >800,000 IU/mL48 weeks24 weeks post-treatmentOne discontinuation of ribavirin due to side effects. 4 patients discontinued PEG-IFN for a short period or a reduced dose was given due to neutropenia.Hemoglobin levels decreased. 2 dose reductions of ribavirin due to decrease in hemoglobin. Nausea caused a minor dose reduction in one additional patients. Working capacity was reduced in all patients. 1 relapse of amphetamine use. Mean weight (range) at baseline, treatment week 12 and treatment week 20 was 80.6 (66.5–109.0), 79.0 (63.5–110.0), and 78.0 (62.9–110.0).
Specific AEs: fatigue 100%, pruritus or dermatitis 90%, nausea 70%, apthous ulcers 30%, oral Candida 20%, blurred vision 2/10, diabetes mellitus 10%, brown spots 10%, migraine 10%.
Shiffman, 2004Before-after573alfa-2a180 μg
1000–1200 mg (weight-based)Nonresponders to standard interferon, with or without ribavirin48 weeks72 weeksDiscontinuation of medication: 0.3% PEG-IFN alone, 7% ribavirin alone, 3% both medications.
Most common AEs leading to dose reduction or discontinuation: hematologic abnormalities, neuropsychiatric events, fatigue, flu-like and other nonspecific symptoms. Infections requiring dose reduction of PEG-IFN occurred in 1% of patients.
Dose reduction required: 15% PEG-IFN, 18% ribavirin, 21% both medications.
Sulkowski, 2002Before-after20alfa-2a180 μg
1000–1200 mg (weight-based)Chronic HCV24–48 weeks (48 weeks for genotype 1 and VR at week 24)12 weeks post-treatment2 withdrawals due to AEs (convulsions and respiratory failure; retinal hemorrhage).Dose reductions of either PEG-IFN or ribavirin in 6 patients (30%).
Specific AEs: myalgia 85%, fatigue 75%, pyrexia 75%, headache 70%, dermatitis 50%, insomnia 45%, rigors 40%, anxiety 35%, nausea 35%, vomiting 35%, anorexia 30%, cough 30%, pruritis 30%, concentration impairment 25%, depression 25%, injection site inflammation 25%, sinusitis 25%, alopecia 20%, appetite decreased 20%, upper abdominal pain 20%, diarrhea 15%, dizziness 15%, dyspnea 15%, nasal congestion 15%, sore throat 15%, weight decreased 15%.
Vere, 2005Before-after37alfa-2a180 μg
1000–1200 mg (weight-based)Chronic HCV48 weeks24 weeks post-treatmentNot reportedAdverse events reported in 21 cases (56.72%): hematologic abnormalities (7 cases, 18.9%), fatigue (5 cases, 13.5%), headache (4 cases, 10.5%), myalgia (2 cases, 5.4%), depression (2 cases, 5.4%), and alopecia (1 case, 2.7%). Hematological abnormalities were anemia (1 case, 2.7%), neutropenia (5 cases, 13.5%), and thrombocytopenia (1 case, 2.7%). During therapy, hemoglobin levels decreased within the first 24 weeks with a mean maximal decrease of approximately 3 g/dl, but only in one case was dose reduction necessary. Hematological abnormalities required dose reduction.
Studies of peginterferon alfa-2b
Bagheri, 2004Prospective, pharmacovigilance87alfa-2b1.5 μg/kg/week800–1200 mg (weight-based)19.6% HIV co-infection, 29.4% genotype 1b, 23.5% genotype 1a, 33.3% had received non-pegylated interferon plus ribavirin48 weeksOne year8/51(15.7%)455 adverse drug reactions reported. Most common were influenza-like symptoms (98%) and asthenia. 58% had GI adverse reactions including diarrhea, constipation, epigastralgia, or loss of appetite. 56% had hematologic adverse reactions. Mean weight loss 4.5 kg (SD 3.0, range 2–18 kg). 44% had musculoskeletal AEs including cramps, myalgia, and dorsalgia. 42% had respiratory AEs including cough, dyspnea, and throat irritation. 38% difficulty in concentration, 18% depression, 12% dizziness, 32% irritability, anxiety, or sleeping disorders. One suicide. 32% injection site reactions, 24% urticaria, 4% photosensitivity, 2% facial flush. 22% disturbances in taste, vision, hearing, or smell.
Ballesteros, 2004Before-after28alfa-2b1.5 μg/kg
800 mgHIV infection24 weeks for HCV genotype 3, 48 weeks for genotypes 1 and 412 weeks post-treatment28.6% discontinued prematurely: 1 in first week, 1 hemolytic anemia, 1 neutropenia, 1 sepsis without neutropenia, 1 peripheral neuropathy, 3 psychiatric disorders.Not reported
Cacoub, 2005Before-after9alfa-2b1.5 μg/kg
800–1200 mg (weight-based)Mixed cryoglobulinemiaMean 13.5 months (SD 2.8 months, range 10-6-33 months) 26 months)Mean 18.6 months (rangeNo discontinuations1 (11%) dose reduction, 1 each leukopenia, thrombocytopenia, depression.
Carnicer, 2005Before-after124alfa-2b1.5 μg/kg
Not reported (weight-based)Non-responders to standard IFN therapy24 weeks72 weeksTreatment discontinuation in 5%Dose reduction in 18%.
Specific AEs: irritation at injection site 82%, flu-like illness, asthenia, myalgia 81%, personality changes 40%, weight loss 40%, anemia, neutropenia, thrombocytopenia 28%, dyspepsia, diarrhea, abdominal pain 25%, depression 20%, cough 17%, pruritus 12%, alopecia 10%, hypothyroidism 4%, pneumonia 2%, chest pain 2%, diabetes mellitus 2%, impotence 2%, bleeding gums 2%, other side effects 10%.
Chang, 2005Before-after115alfa-2bNot reportedNot reported (weight-based)Past alcohol consumption24–48 weeks depending on HCV genotype24 weeks post-treatmentEarly treatment discontinuation in 53 patients.Genotype 1: 25 due to failure to respond. Other reasons: depression (n=10), non-compliance (8), anemia or leucopenia (6), and alcohol relapse (1).
Genotypes 2 and 3: 3 premature discontinuations (1 depression, 1 non-compliance, 1 severe skin rash).
Dalgard, 2004Before-after122alfa-2b1.5 μg/kg
800–1400 mg (weight-based)Genotype 2 or 314 weeks (n=95) or 24 weeks (if no early VR, n=27)24 weeks post-treatmentTreatment stopped early in 6% of patients,Dose of PEG-IFN, RBV, or both, was reduced in 20%. Reasons for early treatment cessation or reduction of dose were neutropenia (n=10), anemia (4), depression (3), fatigue (3), diabetes mellitus (1), and other side effects (10).
Specific AEs (14 week treatment group, 24-week treatment group):
fatigue (48%, 40%), nausea (20%, 8%), depression (22%, 20%), irritability (28%, 28%), alopecia (21%, 24%), influenza-like symptoms (65%, 52%), itching (30%, 12%), exanthema (17%, 8%), anemia (8%, 4%), neutropenia (10%, 4%).
Dan, 2006
Prospective cohort271alfa-2bNot reportedNot reported31.6% cirrhosis.48 weeks24 weeks after treatment completionNot reportedMeasured depression, quality of life, and anemia:
Average SF-36 scores were lower during treatment than at baseline and after treatment. Vitality, physical function, and social functioning scores were significantly lower during treatment. Anemia and depression were both associated with quality of life impairment.
Farel, 2004Prospective cohort23alfa-2b1.5 μg/kg/week1000–1200 mgHIV co-infection48 weeks40–88 weeksNot reportedMeasured ocular changes
8/23 patients developed ophthalmologic pathology: cotton wool spots (n=7), unilateral cataract (n=1), bilateral cataract (n=1), decrease in color vision (n=2; 19% and 50% decrease, respectively).
Gilleece, 2005Before-after27alfa-2b1.5 μg/kg
800–1200 mg (weight-based)HIV positive men who have sex with men24 weeks48 weeksDiscontinuation of all treatment due to AEs: (n=1),Discontinuation due to rising HCV RNA (4).
Adverse events (no dose modification required): anemia (n=1), neutropenia (13), depression (16), fever and rigors (10), insomnia (9), myalgia/arthralgia (6), anxiety (8), fatigue (6), dry skin (3), diarrhea (2), nausea (1), mouth ulcers (1), pain at injection site (1), metallic taste (1), nosebleeds (1), shortness of breath (1).
Glesby, 2005Before-after23alfa-2b1.5 μg/kg
800–1400 mg (weight based)
Also interleukin-2 for 60 weeks
HIV infection48 weeks84 weeks1 withdrawal due to anemia, 1 due to difficulty tolerating peginterferon and ribavirin.(Grade 1=mild, 2=moderate, 3=severe, 4=potentially life-threatening)
18 subjects reported a grade 2 or higher sign or symptom; 3 reported a grade 3 or 4 sign or symptom. 14 developed a grade 2 or higher laboratory toxicity, and 7 developed a grade 3 or 4 toxicity. Grade 3 AEs were fatigue/malaise (n=2), neutropenia (n=2), ache/pain (n=1), diarrhea/loose stools (n=1), and nausea/vomiting (n=1). Grade 4 AEs were neutropenia (n=3), anemia (n=1), and hyperglycemia (n=1).
Hasan, 2004Before-after66alfa-2b1.5 μg/kg
1000–1200 mg (weight-based)Middle Eastern patients infected mainly with HCV genotype 448 weeks24 weeks post-treatment3 patients withdrew due to severe flu-like symptoms.5 patients missed 1 to 3 doses of PEG-IFN. Dose of PEG-IFN was reduced to 1 μg/kg/week in 4 patients (6%).
Specific adverse events: flu-like symptoms 79%, weight loss (>10%) 38%, hair loss 45%, anemia 30%, itching 16%, depression 15%, hypothyroidism 6%, discontinuation 4%.
Kraus, 200598alfa 2b1.5 μg/kg/week800–1200 mg (weight-based)6–12 months, depending on genotype4 weeks after completion of therapyNot reportedMeasured psychiatric side effects.
HADS depression scores increased significantly during treatment and returned to baseline level after termination of antiviral therapy. Hostility also increased during treatment. No differences according to mode of therapy (pegylated vs non-pegylated interferon).
Dose reduction due to weight loss or intolerability in 14.6% of non-pegylated and 14% of peginterferon group.
Marrache, 2005Before-after80alfa-2b0.5 to 1.5 μg/kg/week800–1200 mg (weight-based)Bridging fibrosis or cirrhosis24 weeks for treatment-naïve patients with HCV genotype 2 or 3 (36%), 48 weeks for others24 weeks post-treatmentTreatment discontinued in 18.7%. Causes of treatment discontinuation: asthenia (n=9), depression (1), irritability, insomnia, headaches (1), patient's decision (1), neutropenia (1), spontaneous bacterial infection (1), increase in ALT (1).1 serious AE (spontaneous bacterial peritonitis).
Dose reduction of PEG-IFN in 8.8% due to neutropenia (n=6), and thrombocytopenia (1).
Mauss, 2004Before-after100alfa-2b1.5 μg/kg
1000–1200 mg (weight-based)On methadone maintenance24 weeks for HCV genotype 2 and 3, 48 weeks for genotype 124 weeks post-treatmentDiscontinuation due to AEs or treatment failure did not differ between methadone and control groups. Methadone group: 4 patients discontinued due to AEs (weight loss, impaired renal clearance, anemia, alcohol abuse). Control group: 2 patients discontinued due to AEs (hypothyroidism, first manifestation of multiple sclerosis).At baseline, 6% of patients were treated with antidepressants. During therapy, 25% of patients were treated with antidepressants at any time. At the end of followup, 7% of patients were still on antidepressants.
No increase in median daily methadone dose during treatment (55 mg/day vs 50 mg/day); 24 weeks post-therapy, median methadone dose was lower compared to baseline (20 mg/day vs 55 mg/day, p=0.008).
Mazzaro, 2005Before-after18alfa-2b1.0 μg/kg
1000 mgMixed cryoglobulinemia48 weeks6 months post-treatmentOne patient interrupted treatment after 13 weeks for depression.Dose reduction of PEG-IFN required for 2 patients. Quality of life (EORTC QLC-C30 instrument) showed significant improvement between 24 and 48 weeks in global health status and physical functioning, with a worsening of emotional functioning, mainly for depression. No significant changes in cognitive, social, and role functioning. Improvement of fatigue was observed.
Moreno Planas, 2005Before-after19alfa-2b1.5 μg/kg
10.6 g/kgBiopsy-proven cirrhosis (63.2%) or previous cirrhotic complications (26.3%)24 weeks for HCV genotype 2 and 3 and 48 weeks for genotype 1Mean 21 months1 treatment discontinuation due to cachexia.All patients had AEs. Most commonly reported were asthenia (n=11), weight loss (11), fever (9), anorexia (8), rash (7), nausea and/or vomiting (6). Infectious complications occurred and resolved in 3 patients (1 pneumonia, 1 perineal abscess, and 1 cutaneous cellulitis. Most common hematologic events were leukopenia (n=12), thrombocytopenia (11), and anemia (9). Seven of 11 patients who completed therapy required dose reduction (63.6%). PEG-IFN dose reduced in 4 patients due to leukopenia, and RBV dose in 5 due to anemia.
Moreno, 2004Before-after35alfa-2b50 μg
800 mgHIV-infected48 weeks72 weeks20% discontinued; 17.1% discontinued due to AEs. AEs leading to discontinuation: weight loss >10 kg, lactic acidosis, depression, severe flu-like syndrome, anemia requiring hospitalization and blood transfusion, both depression and flu-like syndrome.Most frequently reported AEs: flu-like symptoms (97%), skin AEs (69%), GI symptoms (34%), irritability (40%), depression (9%), peripheral neuropathy (9%), weight loss >10% (17%), lactic acidosis (6%)
Moreno, 2005Before-after120alfa-2b1.5 μg/kg
at least 10.6 mg/kgHIV-infected, HCV genotype 1; 15.8% liver transplant recipients24–48 weeks72 weeks or until treatment discontinuation11% discontinued treatment due to AEs: (5 HIV infected, 6 HCV monoinfected, 2 liver transplant patients).
8 withdrew between weeks 4 and 24, and 5 before week 48 despite VR at week 24 (4 HCV monoinfected and 1 HIV coinfected).
No treatment withdrawals among liver transplant patients after week 24.
No PEG-IFN dose modifications or withdrawals in first 4 weeks.
Dose adjustments: HCV mono-infected (8.5%), HIV-coinfected (19%), and liver transplant patients (18%).
Muir, 2004Before-after200alfa-2b1.5 μg/kg
1000 mg first 12 weeks, then 800 mgBlacks and non-Hispanic whites48 weeks72 weeksBlacks vs non-Hispanic whites:
Discontinuation: 19% vs 21%;
Rates of AEs, dose reduction, and discontinuation of treatment similar for blacks and non-Hispanic whites.
Blacks vs non-Hispanic whites:
Dose reduction: 22% vs 24%.
Myers, 2004Before-after32alfa-2b1.5 μg/kg
1000–1200 mg (weight-based)HIV-infected, nonresponders to and relapsers to standard interferon48 weeks72 weeks47% withdrew prematurely due to AEs. Psychiatric complications were the most common reason for discontinuation (19%). Reasons for withdrawal: depression (n=3, 1 requiring hospitalization), agitation and delirium (2), anxiety (1), hepatocellular carcinoma (n=1), and non-specific symptoms including fatigue, insomnia, and weight loss (6).Dose reduction of PEG-IFN required in 16%; neutropenia (n=3), anemia (2).
Perez-Olmeda, 2003Before-after68alfa-2b150 μg/week for the first 12 weeks and 100 μg thereafter800 mgChronic HCV6 months for genotype 2 or 3, 12 months for genotypes 1 or 4.6–12 monthsNo discontinuations due to anemia. 2 patients lost 8 kg in 6 months (therapy discontinued).5.5% required dose reduction due to decline in hemoglobin more than 2g/dl. Body weight declined on average 4.6 kg from baseline in patients who completed therapy.
Raison, 2005162alfa 2b1.5 μg/kg/week800 mg (fixed dose) or 1000–1200 mg (weight-based)Compensated liver disease, treatment naïve 58% men, 88% non-Hispanic white, mean age 45.0 (SD 6.7, range 18–70). 77% genotype 1.24 weeks24 weeksNot reported by treatment group, 11/162 overall (6.8%)Measured depression:
Depression (Zung self-rating depression scale) scores were significantly elevated over baseline by week 4 of treatment and remained increased through the 24th week. 38.9% of patients exhibited moderate to severe depression on at least 1 assessment. Only ribavirin dose significantly predicted the development of moderate to severe depression when baseline depression score was controlled for.
Santin, 2006Before-after60alfa-2b80–150 μg
1x/week (weight-based)
800–1200 mg (weight-based)HIV-infected24–48 weeks48–72 weeksDiscontinuation of one or 2 of the drugs in 16.7%.95% had AEs, serious AEs in 16.7%. Dose reduction needed in 11.7%, and Overall AEs: flu-like symptoms 76.6%; weight loss 36.6%; psychiatric disorders 30%; hematological alterations 36.6%; respiratory symptoms 6.6%; dermatological alterations 23.3%
Grade III or IV (serious) events: flu-like symptoms 5%; psychiatric disorders 5%; hematological alterations 5%; respiratory symptoms 1.6%
Cause of treatment discontinuation: flu-like symptoms 3.3%; psychiatric disorders 6.7%; hematological alterations 3.3%; respiratory symptoms 1.7%; dermatological alterations 1.7%
Seow, 2005Before-after33alfa-2b1.5 μg/kg
>10.6 mg/kgChronic HCV24 weeks for HCV genotype 2 and 3 and 48 weeks for genotype 124 weeks post-treatment1 patient stopped treatment prematurely after 24 weeks due to excessive lethargy.Specific AEs: anemia 66.7%, leukopenia 69.7%, thrombocytopenia 45.5%, fatigue 54.5%, fever 48.5%, headache 45.5%, rigors 27.3%, weight decrease 15.2%, arthralgia 27.3%, myalgia 42.4%, anorexia 33.3%, diarrhea 9.1%, nausea 27.3%, giddiness 21.2%, alopecia 33.3%, pruritus 18.2%, rash 9.1%.
Seyam, 2005Retrospective cohort126alfa 2b1.0 to 1.5 μg/kg/week1000–1200 mg (weight-based)48 weeks for genotype 1, 4, 5, and 6, 24 weeks for genotypes 2 and 324 or 48 weeks (end of treatment)Between weeks 12 and 24, 12 patients withdrew due to treatment intolerance and side-effects; not clear how many at earlier time points.Measured weight loss:
91.2% of patients had lost weight at 4 weeks, 93.7% at 12 weeks, 94.7% at 24 weeks, and 89.65% at 48 weeks. Median weight losses were 2.3% of pretreatment weight at 4 weeks, 4.6% at 12 weeks, 6.3% at 24 weeks, and 8.9% at 52 weeks. 12 weeks after completion of treatment, median weight had increased to 96.4% of pretreatment weight, and by 24 weeks this had increased to 99%.
Taliani, 2006Before-after143alfa-2b1.5 μg/kg
1000–1200 mg (weight-based)Nonresponders to a previous course of interferon and ribavirin48 weeks48 weeks19.1% withdrew; 51.9% of those by month 3. AEs leading to discontinuation were hematologic abnormalities (n=9), loss of more than 10% of weight (n=2), ictus (n=1), acute salmonellas (n=1), thyroid dysfunction (n=1), intestinal occlusion (n=1), urticaria (n=1), and severe paresthesia (n=1).Dose reduction of PEG-IFN in 19%. AEs leading to dose reduction were granulocytes and or platelet depletion (21 cases), psychiatric disorders, mainly depression (12 cases), and fever (3 cases).
Voigt, 2006Before-after122alfa-2b1.5 μg/kg
800 mgHIV infection48 weeks for HCV genotypes 1 and 4, and 24 weeks for genotypes 2 and 324 weeks post-treatment30.0% discontinued treatment. Reasons for treatment discontinuation:
patient wish 5.7%, non-compliance 1.6%, lost to followup 1.6%, neuropsychiatric disorders 11.5%, hematological abnormalities 1.6%, flu-like syndrome 2.5%, pleuritis 0.8%, hyperlactatemia 0.8%, cholestatic hepatopathy 0.8%, psoriasis 0.8%, unspecified AE 2.4%.
2 deaths (uncertain circumstances, sudden heart death).
Dose reduction or interruption of ribavirin required in 36%. Patients on zidovudine-containing ART regimens underwent ribavirin dose modifications significantly more often than those on zidovudine-free regimens or no ART (58% vs 29%, p<0.05).
Younossi, 2005Before-after168alfa-2b1.5 μg/kg/week1000–1200 mg; also amantadine 200 mg58.9% nonresponders to previous treatment, 41.1% treatment-naïve24–48 weeks24 weeks post-treatment12 patients (7%) discontinued due to neuropsychiatric side effects (severe depression, anxiety, etc), 2 (1.2%) with recurrent nosebleeds. Other reasons for discontinuation were severe fatigue, flu-like syndrome, inability to work.Significant anemia (hemoglobin <10g.dl) in 11%; severe anemia (<8.5 g/dl) in 0.6%.
Thrombocytopenia (platelet count <50,000) on 0.6%, no severe thrombocytopenia (<25,000); significant neutropenia (ANC <750) in 11%, severe neutropenia (<500) in 3%.
Zeuzem, 2004Before-after235alfa-2b1.5 μg/kg
800–1400 mg (weight based)Low pretreatment viremia (<=600,000 IU/mL)24 weeks48 weeks3% discontinued due to AEs; 2 due to depression and one each for asthenia, anemia, asthenia plus anemia, breast cancer, and psoriasis.Serious AEs in 25 patients (11%).
26% required dose reduction or interruption due to AEs. Anemia (12%), thrombocytopenia (4%), and neutropenia (3%) were most common AEs leading to dose modification.
Zeuzem, 2006Before-after235alfa-2b1.5 μg/kg
800–1400 mgLow baseline HCV-RNA level (<=600,000 IU/mL24 weeks24 weeks3% discontinued due to adverse events (2 depression, asthenia, anemia, asthenia plus anemia, breast cancer, and psoriasis).11% had serious adverse events. Considered related to study medication in 19 of 25 patients (depression, asthenia, abdominal pain, fever, anemia, neutropenia, hypocalcemia, pruritus, rash, psoriasis, allergy, thyroiditis, hearing impairment). 26% required dose reduction or interruption due to adverse events. Most common events leading of dose modifications were anemia (12%), thrombocytopenia (4%), and neutropenia (3%).

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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