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Mechanism Of Action
The pharmacodynamic effects of peginterferon alfa-2b include inhibition of viral replication in virus-infected cells, the suppression of cell cycle progression/cell proliferation, induction of apoptosis, anti-angiogenic activities, and numerous immunomodulating activities, such as enhancement of the phagocytic activity of macrophages, activation of NK cells, stimulation of cytotoxic T-lymphocytes, and the upregulation of the Th1 T-helper cell subset.
PegIntron raises concentrations of effector proteins such as serum neopterin and 2'5' oligoadenylate synthetase, raises body temperature, and causes reversible decreases in leukocyte and platelet counts. The correlation between the in vitro and in vivo pharmacologic and pharmacodynamic and clinical effects is unknown.
Following a single subcutaneous dose of PegIntron, the mean absorption half-life (t ½ ka) was 4.6 hours. Maximal serum concentrations (Cmax) occur between 15 and 44 hours postdose, and are sustained for up to 48 to 72 hours. The Cmax and AUC measurements of PegIntron increase in a dose-related manner. After multiple dosing, there is an increase in bioavailability of PegIntron. Week 48 mean trough concentrations (320 pg/mL; range 0, 2960) are approximately 3-fold higher than Week 4 mean trough concentrations (94 pg/mL; range 0, 416). The mean PegIntron elimination half-life is approximately 40 hours (range 22-60 hours) in patients with HCV infection. The apparent clearance of PegIntron is estimated to be approximately 22 mL/hr·kg. Renal elimination accounts for 30% of the clearance.
Pegylation of interferon alfa-2b produces a product (PegIntron) whose clearance is lower than that of nonpegylated interferon alfa-2b. When compared to INTRON A, PegIntron (1 mcg/kg) has approximately a 7-fold lower mean apparent clearance and a 5-fold greater mean half-life, permitting a reduced dosing frequency. At effective therapeutic doses, PegIntron has approximately 10-fold greater Cmax and 50-fold greater AUC than interferon alfa-2b.
Following multiple dosing of PegIntron (1 mcg/kg subcutaneously given every week for 4 weeks) the clearance of PegIntron is reduced by a mean of 17% in subjects with moderate renal impairment (creatinine clearance 30-49 mL/min) and by a mean of 44% in subjects with severe renal impairment (creatinine clearance 10-29 mL/min) compared to subjects with normal renal function. Clearance was similar in subjects with severe renal impairment not on dialysis and subjects who are receiving hemodialysis. The dose of PegIntron for monotherapy should be reduced in patients with moderate or severe renal impairment [see DOSAGE AND ADMINISTRATION and REBETOL labeling]. REBETOL should not be used in patients with creatinine clearance less than 50 mL/min [see REBETOL labeling, WARNINGS].
During the 48-week treatment period with PegIntron, no differences in the pharmacokinetic profiles were observed between male and female subjects with chronic hepatitis C infection.
The pharmacokinetics of geriatric subjects (65 years of age and older) treated with a single subcutaneous dose of 1 mcg/kg of PegIntron were similar in Cmax, AUC, clearance, or elimination half-life as compared to younger subjects (28-44 years of age).
Population pharmacokinetics for PegIntron and REBETOL (capsules and oral solution) were evaluated in pediatric subjects with chronic hepatitis C between 3 and 17 years of age. In pediatric patients receiving PegIntron 60 mcg/m²/week subcutaneously, exposure may be approximately 50% higher than observed in adults receiving 1.5 mcg/kg/week subcutaneously. The pharmacokinetics of REBETOL (dose-normalized) in this trial were similar to those reported in a prior trial of REBETOL in combination with INTRON A in pediatric subjects and in adults.
Effect of Food on Absorption of Ribavirin
Both AUCtf and Cmax increased by 70% when REBETOL capsules were administered with a high-fat meal (841 kcal, 53.8 g fat, 31.6 g protein, and 57.4 g carbohydrate) in a single-dose pharmacokinetic trial [see DOSAGE AND ADMINISTRATION].
Drugs Metabolized by Cytochrome P-450
The pharmacokinetics of representative drugs metabolized by CYP1A2 (caffeine), CYP2C8/9 (tolbutamide), CYP2D6 (dextromethorphan), CYP3A4 (midazolam), and N-acetyltransferase (dapsone) were studied in 22 subjects with chronic hepatitis C who received PegIntron (1.5 mcg/kg) once weekly for 4 weeks. PegIntron treatment resulted in a 28% (mean) increase in a measure of CYP2C8/9 activity. PegIntron treatment also resulted in a 66% (mean) increase in a measure of CYP2D6 activity; however, the effect was variable as 13 subjects had an increase, 5 subjects had a decrease, and 4 subjects had no significant change [see DRUG INTERACTIONS].
No significant effect was observed on the pharmacokinetics of representative drugs metabolized by CYP1A2, CYP3A4, or N-acetyltransferase. The effects of PegIntron on CYP2C19 activity were not assessed.
The pharmacokinetics of concomitant administration of methadone and PegIntron were evaluated in 18 PegIntron-na´ve chronic hepatitis C subjects receiving 1.5 mcg/kg PegIntron subcutaneously weekly. All subjects were on stable methadone maintenance therapy receiving greater than or equal to 40 mg/day prior to initiating PegIntron. Mean methadone AUC was approximately 16% higher after 4 weeks of PegIntron treatment as compared to baseline. In 2 subjects, methadone AUC was approximately double after 4 weeks of PegIntron treatment as compared to baseline [see DRUG INTERACTIONS].
Use with Ribavirin
Zidovudine, Lamivudine, and Stavudine
Ribavirin has been shown in vitro to inhibit phosphorylation of zidovudine, lamivudine, and stavudine. However, in a trial with another pegylated interferon in combination with ribavirin, no pharmacokinetic (e.g., plasma concentrations or intracellular triphosphorylated active metabolite concentrations) or pharmacodynamic (e.g., loss of HIV/HCV virologic suppression) interaction was observed when ribavirin and lamivudine (n=18), stavudine (n=10), or zidovudine (n=6) were co-administered as part of a multi-drug regimen to HIV/HCV co-infected subjects [see DRUG INTERACTIONS].
Exposure to didanosine or its active metabolite (dideoxyadenosine 5'- triphosphate) is increased when didanosine is co-administered with ribavirin, which could cause or worsen clinical toxicities [see DRUG INTERACTIONS].
Mechanism of Action
The biological activity of PegIntron is derived from its interferon alfa-2b moiety. Peginterferon alfa-2b binds to and activates the human type 1 interferon receptor. Upon binding, the receptor subunits dimerize, and activate multiple intracellular signal transduction pathways. Signal transduction is initially mediated by the JAK/STAT activation, which may occur in a wide variety of cells. Interferon receptor activation also activates NFκB in many cell types. Given the diversity of cell types that respond to interferon alfa-2b, and the multiplicity of potential intracellular responses to interferon receptor activation, peginterferon alfa-2b is expected to have pleiotropic biological effects in the body.
The mechanism by which ribavirin contributes to its antiviral efficacy in the clinic is not fully understood. Ribavirin has direct antiviral activity in tissue culture against many RNA viruses. Ribavirin increases the mutation frequency in the genomes of several viruses and ribavirin triphosphate inhibits HCV polymerase in a biochemical reaction.
The anti-HCV activity of interferon was demonstrated in cell culture using self-replicating HCV-RNA (HCV replicon cells) or HCV infection and resulted in an effective concentration (EC50) value of 1 to 10 IU/mL.
The antiviral activity of ribavirin in the HCV-replicon is not well understood and has not been defined because of the cellular toxicity of ribavirin.
HCV genotypes show wide variability in their response to pegylated recombinant human interferon/ribavirin therapy. Genetic changes associated with the variable response have not been identified.
There is no reported cross-resistance between pegylated/nonpegylated interferons and ribavirin.
A retrospective genome-wide association analysis1,2 of 1671 subjects (1604 subjects from Study 4 [see Clinical Studies] and 67 subjects from another clinical trial) was performed to identify human genetic contributions to anti-HCV treatment response in previously untreated HCV genotype 1 subjects. A single nucleotide polymorphism near the gene encoding interferon-lambda-3 (IL28B rs12979860) was associated with variable SVR rates. The rs12979860 genotype was categorized as CC, CT and TT. In the pooled analysis of Caucasian, African-American, and Hispanic subjects from these trials (n=1587), SVR rates by rs12979860 genotype were as follows: CC 66% vs. CT 30% vs. TT 22%. The genotype frequencies differed depending on racial/ethnic background, but the relationship of SVR to IL28B genotype was consistent across various racial/ethnic groups (see Table 12). Other variants near the IL28B gene (e.g., rs8099917 and rs8103142) have been identified; however, they have not been shown to independently influence SVR rates during treatment with pegylated interferon alpha therapies combined with ribavirin.1
Table 12: SVR Rates by IL28B Genotype*
|Caucasian||69% (301/436)||33% (196/596)||27% (38/139)|
|African-American||48% (20/42)||15% (22/146)||13% (15/112)|
|Hispanic||56% (19/34)||38% (21/56)||27% (7/26)|
|* The SVR rates are the overall rates for subjects treated with PegIntron 1.0 mcg/kg/REBETOL, PegIntron 1.5 mcg/kg/REBETOL and Pegasys 180 mcg/Copegus according to self-reported race/ethnicity.|
Chronic Hepatitis C in Adults
PegIntron Monotherapy - Study 1
A randomized trial compared treatment with PegIntron (0.5, 1, or 1.5 mcg/kg once weekly subcutaneously) to treatment with INTRON A (3 million units 3 times weekly subcutaneously) in 1219 adults with chronic hepatitis from HCV infection. The subjects were not previously treated with interferon alpha, had compensated liver disease, detectable HCV-RNA, elevated ALT, and liver histopathology consistent with chronic hepatitis. Subjects were treated for 48 weeks and were followed for 24 weeks post-treatment.
Seventy percent of all subjects were infected with HCV genotype 1, and 74 percent of all subjects had high baseline levels of HCV-RNA (more than 2 million copies per mL of serum), two factors known to predict poor response to treatment.
Response to treatment was defined as undetectable HCV-RNA and normalization of ALT at 24 weeks post-treatment. The response rates to the 1 and 1.5 mcg/kg PegIntron doses were similar (approximately 24%) to each other and were both higher than the response rate to INTRON A (12%) (see Table 13).
Table 13: Rates of Response to Treatment – Study 1
|A PegIntron 0.5 mcg/kg
|B PegIntron 1 mcg/kg
|C INTRON A 3 MIU three times weekly
|B - C (95% CI) Difference between PegIntron 1 mcg/kg and
|Treatment Response (Combined Virologic Response and ALT Normalization)||17%||24%||12%||11 (5, 18)|
|Virologic Response*||18%||25%||12%||12 (6, 19)|
|ALT Normalization||24%||29%||18%||11 (5, 18)|
|* Serum HCV is measured by a research-based quantitative polymerase chain reaction assay by a central laboratory.|
Subjects with both viral genotype 1 and high serum levels of HCV-RNA at baseline were less likely to respond to treatment with PegIntron. Among subjects with the two unfavorable prognostic variables, 8% (12/157) responded to PegIntron treatment and 2% (4/169) responded to INTRON A. Doses of PegIntron higher than the recommended dose did not result in higher response rates in these subjects. Subjects receiving PegIntron with viral genotype 1 had a response rate of 14% (28/199) while subjects with other viral genotypes had a 45% (43/96) response rate.
Ninety-six percent of the responders in the PegIntron groups and 100% of responders in the INTRON A group first cleared their viral RNA by Week 24 of treatment [see DOSAGE AND ADMINISTRATION].
The treatment response rates were similar in men and women. Response rates were lower in African-American and Hispanic subjects and higher in Asians compared to Caucasians. Although African Americans had a higher proportion of poor prognostic factors compared to Caucasians, the number of non-Caucasians studied (9% of the total) was insufficient to allow meaningful conclusions about differences in response rates after adjusting for prognostic factors.
Liver biopsies were obtained before and after treatment in 60% of subjects. A modest reduction in inflammation compared to baseline that was similar in all 4 treatment groups was observed.
PegIntron/REBETOL Combination Therapy - Study 2
A randomized trial compared treatment with two PegIntron/REBETOL regimens [PegIntron 1.5 mcg/kg subcutaneously once weekly/REBETOL 800 mg orally daily (in divided doses); PegIntron 1.5 mcg/kg subcutaneously once weekly for 4 weeks then 0.5 mcg/kg subcutaneously once weekly for 44 weeks/REBETOL 1000 or 1200 mg orally daily (in divided doses)] with INTRON A [3 MIU subcutaneously thrice weekly/REBETOL 1000 or 1200 mg orally daily (in divided doses)] in 1530 adults with chronic hepatitis C. Interferon-na´ve subjects were treated for 48 weeks and followed for 24 weeks post-treatment. Eligible subjects had compensated liver disease, detectable HCV-RNA, elevated ALT, and liver histopathology consistent with chronic hepatitis.
Response to treatment was defined as undetectable HCV-RNA at 24 weeks post-treatment. The response rate to the PegIntron 1.5 mcg/kg plus REBETOL 800 mg dose was higher than the response rate to INTRON A/REBETOL (see Table 14). The response rate to PegIntron 1.5→0.5 mcg/kg/REBETOL was essentially the same as the response to INTRON A/REBETOL (data not shown).
Table 14: Rates of Response to Treatment – Study 2
|PegIntron 1.5 mcg/kg once weekly REBETOL 800 mg daily||INTRON A 3 MIU three times weekly REBETOL 1000/1200 mg daily|
|Overall response * †||52% (264/511)||46% (231/505)|
|Genotype 1||41% (141/348)||33% (112/343)|
|Genotype 26||75% (123/163)||73% (119/162)|
|* Serum HCV-RNA is measured with a research-based
quantitative polymerase chain reaction assay by a central laboratory.
† Difference in overall treatment response (PegIntron/REBETOL vs. INTRON A/REBETOL) is 6% with 95% confidence interval of (0.18, 11.63) adjusted for viral genotype and presence of cirrhosis at baseline. Response to treatment was defined as undetectable HCV-RNA at 24 weeks post-treatment.
Subjects with viral genotype 1, regardless of viral load, had a lower response rate to PegIntron (1.5 mcg/kg)/REBETOL (800 mg) compared to subjects with other viral genotypes. Subjects with both poor prognostic factors (genotype 1 and high viral load) had a response rate of 30% (78/256) compared to a response rate of 29% (71/247) with INTRON A/REBETOL.
Subjects with lower body weight tended to have higher adverse reaction rates [see ADVERSE REACTIONS] and higher response rates than subjects with higher body weights. Differences in response rates between treatment arms did not substantially vary with body weight.
Treatment response rates with PegIntron/REBETOL were 49% in men and 56% in women. Response rates were lower in African American and Hispanic subjects and higher in Asians compared to Caucasians. Although African Americans had a higher proportion of poor prognostic factors compared to Caucasians, the number of non-Caucasians studied (11% of the total) was insufficient to allow meaningful conclusions about differences in response rates after adjusting for prognostic factors in this trial.
Liver biopsies were obtained before and after treatment in 68% of subjects. Compared to baseline, approximately two-thirds of subjects in all treatment groups were observed to have a modest reduction in inflammation.
PegIntron/REBETOL Combination Therapy - Study 3
In a large United States community-based trial, 4913 subjects with chronic hepatitis C were randomized to receive PegIntron 1.5 mcg/kg subcutaneously once weekly in combination with a REBETOL dose of 800 to 1400 mg (weight-based dosing [WBD]) or 800 mg (flat) orally daily (in divided doses) for 24 or 48 weeks based on genotype. Response to treatment was defined as undetectable HCV-RNA (based on an assay with a lower limit of detection of 125 IU/mL) at 24 weeks post-treatment.
Treatment with PegIntron 1.5 mcg/kg and REBETOL 800 to 1400 mg resulted in a higher sustained virologic response compared to PegIntron in combination with a flat 800 mg daily dose of REBETOL. Subjects weighing greater than 105 kg obtained the greatest benefit with WBD, although a modest benefit was also observed in subjects weighing greater than 85 to 105 kg (see Table 15). The benefit of WBD in subjects weighing greater than 85 kg was observed with HCV genotypes 1-3. Insufficient data were available to reach conclusions regarding other genotypes. Use of WBD resulted in an increased incidence of anemia [see ADVERSE REACTIONS].
Table 15: SVR Rates by Treatment and Baseline Weight –
|Treatment Group||Subject Baseline Weight|
|< 65 kg ( < 143 lb)||65-85 kg (143-188 lb)||> 85-105 kg ( > 188-231 lb)||> 105 kg ( > 231 lb)|
|WBD*||50% (173/348)||45% (449/994)||42% (351/835)||47% (138/292)|
|Flat||51% (173/342)||44% (443/1011)||39% (318/819)||33% (91/272)|
|* P=0.01, primary efficacy comparison (based on data from subjects weighing 65 kg or higher at baseline and utilizing a logistic regression analysis that includes treatment [WBD or Flat], genotype and presence/absence of advanced fibrosis, in the model).|
A total of 1552 subjects weighing greater than 65 kg in Study 3 had genotype 2 or 3 and were randomized to 24 or 48 weeks of therapy. No additional benefit was observed with the longer treatment duration.
PegIntron/REBETOL Combination Therapy - Study 4
A large randomized trial compared the safety and efficacy of treatment for 48 weeks with two PegIntron/REBETOL regimens [PegIntron 1.5 mcg/kg and 1 mcg/kg subcutaneously once weekly both in combination with REBETOL 800 to 1400 mg PO daily (in two divided doses)] and Pegasys 180 mcg subcutaneously once weekly in combination with Copegus 1000 to 1200 mg PO daily (in two divided doses) in 3070 treatment-na´ve adults with chronic hepatitis C genotype 1. In this trial, lack of early virologic response (undetectable HCV-RNA or greater than or equal to 2 log10 reduction from baseline) by treatment Week 12 was the criterion for discontinuation of treatment. SVR was defined as undetectable HCV-RNA (Roche COBAS TaqMan assay, a lower limit of quantitation of 27 IU/mL) at 24 weeks post-treatment (see Table 16).
Table 16: SVR Rates by Treatment – Study 4
|PegIntron 1.5 mcg/kg/ REBETOL||PegIntron 1 mcg/kg/ REBETOL||Pegasys 180 mcg/Copegus|
|SVR||40% (406/1019)||38% (386/1016)||41% (423/1035)|
Overall SVR rates were similar among the three treatment groups. Regardless of treatment group, SVR rates were lower in subjects with poor prognostic factors. Subjects with poor prognostic factors randomized to PegIntron (1.5 mcg/kg)/REBETOL or Pegasys/Copegus, however, achieved higher SVR rates compared to similar subjects randomized to PegIntron 1 mcg/kg/REBETOL. For the PegIntron 1.5 mcg/kg plus REBETOL dose, SVR rates for subjects with and without the following prognostic factors were as follows: cirrhosis (10% vs. 42%), normal ALT levels (32% vs. 42%), baseline viral load greater than 600,000 IU/mL (35% vs. 61%), 40 years of age and older (38% vs. 50%), and African American race (23% vs. 44%). In subjects with undetectable HCV-RNA at Week 12 who received PegIntron (1.5 mcg/kg)/REBETOL, the SVR rate was 81% (328/407).
PegIntron/REBETOL Combination Therapy in Prior Treatment Failures - Study 5
In a noncomparative trial, 2293 subjects with moderate to severe fibrosis who failed previous treatment with combination alpha interferon/ribavirin were re-treated with PegIntron, 1.5 mcg/kg subcutaneously, once weekly, in combination with weight adjusted ribavirin. Eligible subjects included prior nonresponders (subjects who were HCV-RNA positive at the end of a minimum 12 weeks of treatment) and prior relapsers (subjects who were HCVRNA negative at the end of a minimum 12 weeks of treatment and subsequently relapsed after post-treatment follow-up). Subjects who were negative at Week 12 were treated for 48 weeks and followed for 24 weeks post-treatment. Response to treatment was defined as undetectable HCV-RNA at 24 weeks post-treatment (measured using a research-based test, limit of detection 125 IU/mL). The overall response rate was 22% (497/2293) (99% CI: 19.5, 23.9). Subjects with the following characteristics were less likely to benefit from re-treatment: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection.
The re-treatment sustained virologic response rates by baseline characteristics are summarized in Table 17.
Table 17: SVR Rates by Baseline Characteristics of
Prior Treatment Failures
|HCV Genotype/ Metavir Fibrosis Score||Overall SVR by Previous Response and Treatment|
|alfa interferon/ribavirin % (number of subjects)||peginterferon (2a and 2b combined)/ribavirin % (number of subjects)||alfa interferon/ribavirin % (number of subjects)||peginterferon (2a and 2b combined)/ribavirin % (number of subjects)|
|Overall||18 (158/903)||6 (30/476)||43 (130/300)||35 (113/344)|
|HCV 1||13 (98/761)||4 (19/431)||32 (67/208)||23 (56/243)|
|F2||18 (36/202)||6 (7/117)||42 (33/79)||32 (23/72)|
|F3||16 (38/233)||4 (4/112)||28 (16/58)||21 (14/67)|
|F4||7 (24/325)||4 (8/202)||26 (18/70)||18 (19/104)|
|HCV 2/3||49 (53/109)||36 (10/28)||67 (54/81)||57 (52/92)|
|F2||68 (23/34)||56 (5/9)||76 (19/25)||61 (11/18)|
|F3||39 (11/28)||38 (3/8)||67 (18/27)||62 (18/29)|
|F4||40 (19/47)||18 (2/11)||59 (17/29)||51 (23/45)|
|HCV 4||17 (5/29)||7 (1/15)||88 (7/8)||50 (4/8)|
Achievement of an undetectable HCV-RNA at treatment Week 12 was a strong predictor of SVR. In this trial, 1470 (64%) subjects did not achieve an undetectable HCV-RNA at treatment Week 12, and were offered enrollment into long-term treatment trials, due to an inadequate treatment response. Of the 823 (36%) subjects who were HCV-RNA undetectable at treatment Week 12, those infected with genotype 1 had an SVR of 48% (245/507), with a range of responses by fibrosis scores (F4-F2) of 39-55%. Subjects infected with genotype 2/3 who were HCV-RNA undetectable at treatment Week 12 had an overall SVR of 70% (196/281), with a range of responses by fibrosis scores (F4-F2) of 60-83%. For all genotypes, higher fibrosis scores were associated with a decreased likelihood of achieving SVR.
Chronic Hepatitis C In Pediatrics
PegIntron/REBETOL Combination Therapy - Pediatric Trial
Previously untreated pediatric subjects 3 to 17 years of age with compensated chronic hepatitis C and detectable HCV-RNA were treated with REBETOL 15 mg/kg/day plus PegIntron 60 mcg/m² once weekly for 24 or 48 weeks based on HCV genotype and baseline viral load. All subjects were to be followed for 24 weeks post-treatment. A total of 107 subjects received treatment, of which 52% were female, 89% were Caucasian, and 67% were infected with HCV genotype 1. Subjects infected with genotype 1, 4 or genotype 3 with HCV-RNA greater than or equal to 600,000 IU/mL received 48 weeks of therapy while those infected with genotype 2 or genotype 3 with HCV-RNA less than 600,000 IU/mL received 24 weeks of therapy. The trial results are summarized in Table 18.
Table 18: SVR Rates by Genotype and Treatment Duration
– Pediatric Trial
|24 Weeks Virologic Response N* † (%)||48 Weeks Virologic Response N* † (%)|
|All||26/27 (96.3)||44/80 (55.0)|
|3‡||12/12 (100)||2/3 (66.7)|
|* Response to treatment was defined as undetectable
HCV-RNA at 24 weeks post-treatment.
† N = number of responders/number of subjects with given genotype, and assigned treatment duration.
‡ Subjects with genotype 3 low viral load (less than 600,000 IU/mL) were to receive 24 weeks of treatment while those with genotype 3 and high viral load were to receive 48 weeks of treatment.
1. Ge, D., Fellay, J., Thompson, A.J., Simon, J.S., Shianna, K.V., Urban, T.J., Heinzen, E.L., Qiu, P., Bertelsen, A.H., Muir, A.J., Sulkowski, M., McHutchison, J.G., Goldstein, D.B., Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance, Nature 2009;461(7262):399- 401.
2. Thompson, A.J., Muir, A.J., Sulkowski, M.S., Ge, D., Fellay, J., Shianna, K.V., Urban, T., Afdhal, N.H., Jacobson, I.M., Esteban, R., Poordad, F., Lawitz, E.J., McCone, J., Shiffman, M.L., Galler, G.W., Lee, W.M., Reindollar, R., King, J.W., Kwo, P.Y., Ghalib, R.H., Freilich, B., Nyberg, L.M., Zeuzem, S., Poynard, T., Vock, D.M., Pieper, K.S., Patel, K., Tillmann, H.L., Noviello, S., Koury, K., Pedicone, L.D., Brass, C.A., Albrecht, J.K., Goldstein, D.B., McHutchison, J.G., Interlukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus, Gastroenterology 2010;139:120-129.
Last reviewed on RxList: 6/1/2015
This monograph has been modified to include the generic and brand name in many instances.
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