PEG-Interferon Alfa-2a/2b and IFNL3

Sean Bennett, Pharm.D. Candidate; Hannah Stewart, Pharm.D. Candidate; Elise Smith, Pharm.D. Candidate; Alan Luo, Pharm.D. Candidate.

About the Drug

PEG-Interferon Alfa-2a (PEG-IFN alfa 2a, Intron® A) and PEG-Interferon Alfa-2b (PEG-IFN alfa 2b, PEG- Intron, Unitron PEG) are drugs made to mimic parts of our immune system called interferons. These interferons are released when your body senses an infection in the body and can help to stop the infection from spreading.

Manufactured interferons are used to treat several different conditions, and most of these are viral infections. PEG-Interferon Alfa-2a is FDA indicated for the treatment of hepatitis B and C, which are viral infections that cause inflammation of the liver. PEG-Interferon Alfa-2b is indicated for the treatment of hepatitis C, and has an additional indication as adjunct treatment for malignant melanoma which is a certain type of skin cancer.

About the Gene

The gene of interest for PEG-Interferon Alfa is the interferon lambda 3 gene (IFNL3). This gene makes a type of interferon that is expressed in different areas of the body. The way in which the INFL3 gene affects the effectiveness of interferon therapy is not well understood. However, the cooperative effects of the interferons made by IFNL3 may enhance the patient’s response to therapy.

About the Drug-Gene Interaction

INFL3 genotype is the best indicator of a patient’s response to PEG-IFN therapy. Patients that have the most favorable variation (called “CC”) have approximately 70% likelihood of achieving therapeutic success. These patients are considered good candidates for PEGInterferon Alfa 2a/2b. Those patients who have the “CT” or “TT” versions possess genes with a decreased activity level. These individuals only have a 30% likelihood of achieving therapeutic success. These patients should be evaluated and may need to consider another therapy option.

Drug-Gene Interaction Example

Vincent is a 42 year old white male whom was recently diagnosed with a chronic hepatitis C infection (HCV). His doctors have decided that he is eligible for Interferon therapy and have decided to start him on Peg-Interferon alfa-2a with ribavirin therapy after finding he has a certain form of hepatitis C virus that responds well to this therapy. His doctor also recommended that Vincent should get additional testing for the IFNL3 gene, as that would increase his chances of treatment success. However, Vincent declined additional testing citing potential costs and that he didn’t think it was “necessary”. After 48 weeks of treatment, Vincent’s test results for his Hepatitis C virus came back. His doctor notified him that he still had a significant amount of virus in his blood, and that an alternate therapeutic regimen was suggested.

If Vincent had chosen to test for the IFNL3 gene, his doctor would have found that he had the unfavorable response genotype “TT”. Had he and his doctor of known this, they would have elected to choose another treatment regimen. Both Vincent and his physician would have saved both the costs and time spent in treating his disease.

IFNL3 genetic testing does not completely rule out the risks of taking Peg-Interferon alfa-2a based therapies, nor will it guarantee that the patient will achieve therapeutic success. IFNL3 testing is a way personalize the treatment of patients and maximize the effectiveness while decreasing costs of treatment as well as the potential harm to the patient.

Provider Information

The links below provide access to important articles and information relative to PEG-interferon Alfa-2a/2b. The links are to external websites and will be checked regularly for consistency.

Sources of Information

Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. c2015 [cited 2015 May 2]. Available from: http://0-www.clinicalpharmacology-

DailyMed [Internet]. Bethesda (MD): U.S. National Library of Medicine; c1993-2015. PEGASYS - peginterferon alfa-2a injection, solution; [cited 2015 Nov 23]; [about 5 screens]. Available from: 4e22-84bb- 869e13600440/.

DailyMed [Internet]. Bethesda (MD): U.S. National Library of Medicine; c1993-2015. PEGINTRON - peginterferon alfa-2b; [cited 2015 Nov 23]; [about 5 screens]. Available from: 467f-acb8- 67ef62cf8dac/.

DRUGDEX® [Internet]. Greenwood Village (CO): Thomson Reuters Inc. c1974-2015 [cited 2015 Jan 15]. Available at:

Geer LY, Marchler-Bauer A, Geer RC, Han L, He J, He S, Liu C, Shi W, Bryant SH. The NCBI BioSystems database. Nucleic Acids Res. 2010 Jan;38:D492-6.

Muir A, Gong L, Johnson SG, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for INFL3 (IL28B) genotype and PEG interferon-alpha-based regimens. Clin Pharmacol Ther. 2014;95:141-46.

Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, Altman RB, Klein TE. Pharmacogenomics Knowledge for Personalized Medicine. Clin Pharmacol Ther. 2012;92(4):414-417.