This document summarizes coverage criteria and guidelines for various alpha interferon products used to treat conditions such as chronic hepatitis B, chronic hepatitis C, melanoma, and myeloproliferative neoplasms. It provides details on covered medications, their uses, prior authorization rationale and criteria, benefit design, and coverage duration and renewal. References include clinical practice guidelines and studies supporting the use of pegylated interferons for hepatitis C and interferon for other conditions.

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Alpha Interferon Products
To Initiate a Coverage Review, Call 1-800-753-2851
Covered Medications
 Interferon alfacon-1 (Infergen )
 Interferon alpha-2b (Intron-A )
 Peginterferon alfa-2b (Sylatron )
 Interferon alpha-n3 (Alferon N )
What they do and how they are used
 Interferons are a family of proteins that may enhance or suppress the immune system. They have complex
antiviral, antineoplastic (anti-cancer), and immunomodulating activities. Interferons are often referred to as
biologic response modifiers. They are used in the treatment of various neoplasms and viral infections.
 Interferon alfacon-1 (Infergen) is comprised of the most frequently repeating amino acid pairs occurring in
the natural alpha interferon subtypes and is used to treat chronic hepatitis B and chronic hepatitis C.
 Evidence and clinical practice guidelines support the use of pegylated interferons over non-pegylated
interferons in treatment of chronic hepatitis C, with higher adherence and sustained virologic response
(SVR) rates.
 Peginterferon alfa-2b has been specifically formulated in single use, self-administered injections as
Sylatron for the weekly treatment of advanced melanoma to be given for up to five years.
 Chronic hepatitis C (CHC) is caused by a RNA virus that infects the liver. CHC infection can lead to
cirrhosis, liver failure, and liver cancer. Treatment of hepatitis C virus (HCV) is aimed at reducing the
progression of the disease to cirrhosis and decreasing the risk of liver cancer by achieving a decrease in
the hepatitis C viral level.
 All treatment-naïve patients with compensated chronic liver disease related to HCV who are willing to be
treated and have no contraindication to peginterferon alfa or ribavirin should be considered for therapy.
Rationale for prior authorization
To provide coverage for alpha interferon products for the treatment of conditions for which they have shown to
be effective and to help prevent their use for conditions for which the effectiveness is not known. The coverage
review process is also intended to limit exposure to excessive duration of coverage outside that which is
referenced in widely accepted clinical treatment guidelines.
Benefit design
Coverage is determined through prior authorization for every claim.
Coverage authorization criteria
Coverage for Interferon alfa-2b (Intron-A ) is provided for treatment of the following:
Chronic hepatitis B
Hairy cell leukemia
Kaposi’s sarcoma (in the presence of CD4 T-cell count ≥ 200 cells/mm
3
or asymptomatic patients with no
history of serious opportunistic infection)
Malignant melanoma
Multiple myeloma
Non-Hodgkin’s lymphoma
Renal cell carcinoma
Condyloma acuminata (genital warts) in situations where conventional therapy has not been effective
Myeloproliferative neoplasms (chronic myeloid leukemia, essential thrombocytosis, myelofibrosis, and
polycythemia vera)
Folicular lymphoma
Chronic hepatitis C
Acute hepatitis C (if it has been at least 8 weeks since onset)
Bone cancer, giant cell tumor of the bone
Central nervous system (CNS) Cancers (i.e., leptomenigeal metastases and meningioma)

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Chronic myeloid leukemia (CML) in patients unable to tolerate tyrosine kinase inhibitors (TKIs) or for use
in post-transplant patients
Carcinoid Tumors
Soft tissue sarcoma – desmoids tumors (aggressive fibromatosis)
Neoplasm of conjunctiva or neoplasm of cornea
Coverage for Interferon alfacon-1 (Infergen ) is provided for treatment of the following:
Chronic hepatitis B
Chronic hepatitis C
Coverage for Peginterferon alfa-2b (Sylatron ) is provided for the following:
Stage III, resected melanoma
Stage IIB or C melanoma
Bone cancer, giant cell tumor of the bone
Coverage for Interferon alpha-n3 (Alferon N ) is provided for the following::
Condyloma acuminata (genital warts) in situations where conventional therapy has not been effective
Chronic hepatitis C
Coverage duration:
Coverage for Intron A is provided for 12 months.
Coverage for Infergen is provided for 12 months.
Coverage for Sylatron is provided for 12 months. Coverage may be renewed.
Coverage for Alferon N is provided for 12 months.
References
Product Information
 Boceprevir (Victrelis™) Prescribing Information. Whitehouse Station, NJ: Merck and Co., May 2011.
 Interferon alfa-n3 (Alferon N). Prescribing information. Hemispherx Biopharma. Accessed 24 June 2011. Available
from URL: http://www.hemispherx.net/content/products/alferon_insert.htm#TOP
 Interferon alpha – 2b (Intron A) Whitehouse Station, NJ: Schering, 2008.
 Interferon alfacon-1 (Infergen ). Prescribing information. Warrendale, PA: Three Rivers, LLC, June, 2010.
 Peginterferon alfa-2b (Sylatron ). Prescribing information. Kenilworth, NJ: Schering, March, 2011.
 Telaprevir (Incivek™) Prescribing Information Cambridge, MA: Vertex Pharmaceuticals, Inc., May 2011.
Chronic Hepatitis B
 Chan HL, Leung NW, Hui AY, et al. A randomized, controlled trial of combination therapy for chronic hepatitis B;
comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone. Ann Intern Med 2005;142(4):240-50.
 Zheng Y, Zhao L, Wu T, Guo S, Chen Y, et al. Efficacy of consensus interferon in treatment of HbeAg-positive chronic
hepatitis B: a multicentre, randomized controlled trial. Virol J. 2009 Jul 9;6:99.
Chronic Hepatitis C
 American Association for the Study of Liver Diseases (AASLD). Ghany MG, Nelson, DR, Strader DB, Thomas DL,
Seeff LB. An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline.
Hepatology 2011;54(4):1433-1444.
 American Association for the Study of Liver Diseases (AASLD). Ghany M, Strader DB, Wright T, Thomas DL, Seeff LB.
Practice Guideline: Diagnosis, management, and treatment of hepatitis C: An Update. Hepatology 2009;49:1335-1374.
 Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costanzo GG, Lanza AG, Picciotto FP, Marino-Marsilia G,
Fontanella L, Leandro G. Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin
for treating chronic hepatitis C virus infection. Gastroenterology. 2010 Jan;138(1):116-22. Epub 2009 Oct 20.
 Bacon BR, Shiffman ML, Mendes F, et al. Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after
nonresponse to pegylated interferon/ribavirin: DIRECT results. Hepatology 2009;49(6):1838-46.
 Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC, Lee WM, Lok AS, Bonkovsky HL,
Morgan TR, Ghany MG, Morishima C, Snow KK, Dienstag JL; HALT-C Trial Investigators. Prolonged therapy of
advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med. 2008 Dec 4;359(23):2429-41.
 European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of Hepatitis C Virus
Infection. J Hepatol 2011; 55: 245-264. Accessed 24 June 2011. Available from URL: http://www.easl.eu/_clinical-

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practice-guideline
 Gordon F, Brown R, Kwo P, et al. Peginterferon Alfa-2B and Ribavirin for Hepatitis C recurrence post orthotopic liver
transplantation (OLT): Final results from the PROTECT Study. The International Liver Congress 2010. Vienna,
Austria. 15 Apr 2010.
 Heathcote E, Shiffman M, Cooksley G, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N
Engl J Med 2000;343:1673-80.
 Keeffe EB, Hollinger FB, The Consensus Interferon Study Group. Therapy of hepatitis C: consensus interferon trials.
Hepatology 1997;26(Suppl1):101S-107S.
 McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial
treatment for chronic hepatitis C. N Engl J Med 1998;339(21):1485-1492.
 McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, Lee WM, Ghalib RH, Schiff ER,
Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K, Noviello S, Pedicone LD, Brass CA, Albrecht JK,
Sulkowski MS; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection.
N Engl J Med. 2009 Aug 6;361(6):580-93. Epub 2009 Jul 22.
 National Institutes of Health Consensus Development Conference Statement. Management of hepatitis C:2002.
National Institutes of Health June 12, 2002.
 Reichard O, Norkrans G, Frydén A, et al. Randomized, double-blind, placebo-controlled trial of interferon -2b with
and without ribavirin for chronic hepatitis c. Lancet 1998;351:83-87.
 Reichard O, Schvarcz R, Weiland O. Therapy of hepatitis C: alpha interferon and ribavirin. Hepatology 1997;26(Suppl
1):108S-111S.
 Rumi MG, Aghemo A, Prati GM, D'Ambrosio R, Donato MF, Soffredini R, Del Ninno E, Russo A, Colombo M.
Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b plus ribavirin in chronic hepatitis C.
Gastroenterology. 2010 Jan;138(1):108-15. Epub 2009 Sep 18.
 Tong MJ, Reddy KR, Lee WM, et al. Treatment of chronic hepatitis C with consensus interferon: a multicenter,
randomized, controlled trial. Hepatology 1997;26(3):747-754.
Chronic Myelogenous Leukemia
 Guilhot F, Abgrall J-F, Harousseau J-L, et al. A multicentric randomised study of alpha 2b interferon (ifn) and
hydroxyurea (hu) with or without cytosine-arabinoside (ara-c) in previously untreated patients with ph+ chronic
myelocytic leukemia (cml): preliminary cytogenic results. Leukemia and Lymphoma 1993;11 Suppl 1:181-183.
 Guilhot F, Chastang C, Michallet M, et al. Interferon alfa-2b combined with cytarabine versus interferon alone in
chronic myelogenous leukemia. N Engl J Med 1997;337(4):223-229.
 Hehlmann R, Heimpel H, Hasford HJ, et al. Randomized comparison of interferon- with busulfan and hydroxyurea in
chronic myelogenous leukemia. The American Society of Hematology 1994;84(12):4064-4077.
 Morra E, Alimena G, Lazzarino M, et al. Evolving modalities of treatment with interferon alfa-2b for ph
1
-positive chronic
myelogenous leukaemia. Eur J Cancer 1991;27 Suppl 4:S14-S17.
 Niederle N, Moritz T, Kloke O, et al. Interferon alfa-2b in acute- and chronic-phase chronic myelogenous leukaemia:
initial response and long-term results in 54 patients. Eur J Cancer 1991;27 Suppl 4:S7-S14.
 Ohnishi K, Ohno R, Tomonaga M, et al. A randomized trial comparing interferon- with busulfan for newly diagnosed
chronic myelogenous leukemia in chronic phase. The American Society of Hematology 1995;86(3):906-916.
 Ozer H, George SL, Schiffer CA, et al. Prolonged subcutaneous administration of recombinant 2b interferon in
patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia:
effect on remission duration and survival: cancer and leukemia group b study 8583. The American Society of
Hematology 1993;82(10):2975-2984.
Myeloproliferative Neoplasms
 Gilbert HA. Long term treatment of myeloproliferative disease with interferon- -2b. Cancer. 1998;83(6):1205-1213.
 Jabbour E, Kantarjian H, Cortes J, et al. PEG-IFN-alpha-2b therapy in BCR-ABL-negative myeloproliferative disorders:
final result of a phase 2 study. Cancer. 2007 Nov 1;110(9):2012-8.
 Kiladjian JJ, Cassinat B, Chevret S, et al. Pegylated interferon-alfa-2a induces complete hematologic and molecular
responses with low toxicity in polycythemia vera. Blood. 2008 Oct 15;112(8):3065-72.
 Lengfelder E, Griesshammer M, Hehlmann R. Interferon-alpha in the treatment of essential thrombocythemia.
Leukemia and Lymphoma 1996;22, Suppl 1:135-142.
 Quintas-Cardama A, Kantarjian H, Manshouri T, et al. Pegylated interferon alfa-2a yields high rates of hematologic
and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol
2009:; Nov 10:27 (32):5418-24
 Tefferi A, Elliott M.A., Solberg Jr. L.A., et al. New drugs in essential thrombocythemia and polycythemia vera. Blood
Reviews 1997;11:1-7.
Non-Hodgkin’s Lymphoma
 Chisesi T, Congiu M, Contu A, et al. Randomized study of chlorambucil (cb) compared to interferon (alfa-2b) combined
with cb in low-grade non-hodgkin’s lymphoma: an interim report of a randomized study. Eur J Cancer 1991;27 Suppl
4:S31-S33.
 Foon KA, Sherwin SA, Abrams PG, et al. Treatment of advanced non-hodgkin’s lymphoma with recombinant leukocyte
a interferon. N Engl J Med 1984;311:1148-1152.
 Smalley RV, Anderson JW, Hawkins MJ, et al. Interferon alpha combined with cytotoxic chemotherapy for patients with

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non-hodgkin’s lymphoma. N Engl J Med 1992;327:1336-1341.
 Solal-Celigny P, Lepage E, Brousse N, et al. Recombinant interferon alfa-2b combined with a regimen containing
doxorubicin in patients with advanced follicular lymphoma. N Engl J Med 1993;329:1608-1614.
 Steis RG, Foon KA, Longo DL. Current and future uses of recombinant interferon alpha in the treatment of low-grade
non-hodgkin’s lymphoma. Cancer 1987;59:658-663.
Renal Cell Carcinoma
 Hofmockel G, Tack W, Frohmüller HGW. Cyclic interferon alpha treatment in metastatic renal cell carcinoma: results
of a phase 2 study and review of the literature. Urol Int 1997;58:8-12.
 Oliver RTD. Renal cell cancer: is there long-term survival advantage from cytokine treatment. Eur J Cancer
1994;30A(9):1214-1216.
 Papadopoulos I, Rudolph P, Weichert-Jacobsen K, et al. Prognostic indicators for response to therapy and survival in
patients with metastatic renal cell cancer treated with interferon alpha-2 beta and vinblastine. Urology 1996;48:373-
378.
 Tsavaris N, Mylonakis N, Bacoyiannis C, et al. Treatment of renal cell carcinoma with escalating doses of alpha-
interferon. Chemotherapy 1993;39:361-366.