Effective Date:

a)    This policy will apply to all services performed on or after the above revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply

Interferons are used for a variety of medical problems. They are approved for benefits for some diagnoses.

Preauthorization may be required.

PEGylated interferon alpha 2B (Peg Intron) is not covered for the treatment of Hepatitis C.  Pegasys (PEGylated interferon alpha 2A) should be used instead.

Interferons are considered specialty medications and are covered under the specialty drug benefit.  Most products are covered under the pharmacy benefit.

I.  Interferon Alpha

Interferon Alpha is considered medically necessary for the following indications:

1)    AIDS-associated Kaposi`s sarcoma;

2)    Basal cell carcinoma, when surgical intervention is contraindicated (interferon therapy in basal cell carcinoma is only considered medically necessary for those persons in which surgical intervention is contraindicated; surgical intervention is considered first-line therapy for basal cell carcinoma, and has been shown to have a 95% treatment success rate);

3)    Carcinoid syndrome;

4)    Cervical carcinoma, in persons who cannot tolerate, or whose tumor is resistant to, standard first-line therapy;

5)    Chronic myelogenous leukemia;

6)    Colorectal carcinoma, when used in conjunction with 5-FU;

7)    Condylomata Acuminata (genital warts) (intralesional only);

8)    Cutaneous T-cell lymphoma (including mycosis fungoides);

9)    Desmoids tumors (fibromatosis), for unresectable disease or gross residual disease following surgery;

10)   Essential Thrombocythemia;

11)   Hairy cell leukemia;

12)   Hepatitis C (non-A, non-B hepatitis), in persons with compensated liver disease (Child-Pugh score less than or equal to 6 [class A]) (the safety and efficacy have not been established for treatment of persons with decompensated liver disease). Continued treatment with interferon alpha is considered not medically necessary for persons with HCV genotypes 1 and 4 through 6 who have failed to attain an early virologic response after 12 weeks of treatment (where early virologic response is indicated by achievement of at least a 100-fold (2 log10) decrease in serum HCV from pretreatment baseline). Up to a maximum of 24 weeks of interferon alpha is considered medically necessary for persons with HCV genotypes 2, 3, and 7 through 10; and up to a maximum of 48 weeks of interferon alpha is considered medically necessary for persons with HCV genotypes 1 and 4 through 6. A course of standard interferon alpha in persons with hepatitis C who have failed to respond or relapsed after an adequate course of PEGylated interferon alpha or consensus interferon is considered experimental and investigational because of a lack of evidence on the effectiveness of standard interferon in these persons. Note: Upon medical review, extended treatment with interferon alpha beyond these limits may be considered medically necessary for persons with cryoglobulinemia and for liver transplant recipients with recurrent hepatitis C infection;

13)   Hepatocellular carcinoma, for persons with hepatitis C and completely resected tumors;

14)   Hyper-eosinophilic syndrome that is not adequately responsive to glucocorticoids;

15)   Kasabach-Merritt syndrome;

16)   Life-threatening hemangioma of infancy (intralesional) when member is intolerant of, or the hemangioma is resistant to, corticosteroid therapy;

17)   Malignant melanoma;

18)   Meningioma, recurrent, surgically inaccessible; 

19)   Malignant mesothelioma in persons who have relapsed following surgery and failed treatment with or cannot tolerate first-line chemotherapy;

20)   Multiple myeloma, solitary plasmacytoma, or systemic light chain amyloidosis;

21)   non-Hodgkin`s lymphoma (including adult T-cell lymphoma (chronic, smoldering or acute) and mycosis fungoides/Sezary syndrome);

22)   Ocular herpes simplex (interferon alpha eye drops);

23)   Ovarian carcinoma, in persons who cannot tolerate, or whose tumor is resistant to, standard first-line therapy;

24)   Pancreatic islet cell carcinoma;

25)   Persons with chronic hepatitis B who meet all of the following criteria:

a.  Member has compensated liver disease (Child-Pugh score less than or equal to 6

[class A]); and 

b.  Serum aminotransferase (AST) greater than double the upper limit of normal range (AST normal range 0-35 u/l).

A course of standard interferon alpha in persons with hepatitis B who have failed an adequate course of PEGylated interferon alpha is considered experimental and investigational because of a lack of evidence on the effectiveness of standard interferon in these persons.

(The use of interferon alpha is considered contraindicated in the following persons with hepatitis B: those who are HIV positive; hepatitis B surface antigen (HBs Ag) positive persons undergoing liver transplantation; and those with a history of or currently active autoimmune hepatitis);

                    26)  Persons with polycythemia vera who meet all of the following criteria:

·      Oral therapy with hydroxyurea or other myelosuppressive agent is not effective, not tolerated, or is contraindicated; and

·      Phlebotomy is not effective, not tolerated, or contraindicated.

Note: Failure of phlebotomy and/or myelosuppressive agents may be defined as any of the following:

o  Lack of hematological control (e.g., hematocrit greater than 45 or platelet count greater than 600 x 109/L);

o  Occurrence of intractable symptoms (e.g., headaches, pruritus);

o  Occurrence of symptoms related to hepatosplenomegaly;

o  Occurrence of thrombotic or hemorrhagic complications; or

o  Phlebotomy required more often than once every two months.

27)   Renal cell carcinoma;

28)   Respiratory papillomatosis;

29)   Superficial bladder cancer (carcinoma in situ of the bladder);

30)   Vulvar Vestibulitis, or

31)   Waldenstrom`s Macroglobulinemia.

B. Interferon Alpha is considered medically necessary in some instances of the following conditions, and prepayment review will be routinely performed:

1)    Ovarian carcinoma, in persons who cannot tolerate, or whose tumor is resistant to, standard first-line therapy;

2)    Chronic myelogenous leukemia (not in accelerated phase);

3)    Low-grade non-Hodgkin`s lymphoma (stage III/IV) especially follicular small cleaved cell lymphoma (nodular poorly differentiated types);

4)    Colorectal carcinoma, when used in conjunction with 5-FU;

5)    Cervical carcinoma, in persons who cannot tolerate, or whose tumor is resistant to, standard first-line therapy;

6)    Superficial bladder cancer (carcinoma in situ of the bladder);

7)    Basal cell carcinoma, only when surgical intervention is contraindicated

8)    Life-threatening hemangioma of infancy (intralesional) when member is intolerant of, or the hemangioma is resistant to, corticosteroid therapy;

C. Interferon Alpha is considered medically necessary in some instances of the following conditions; pre-authorization is required:

1)    Persons with polycythemia vera who meet all of the following criteria:

·      Phlebotomy is not effective, not tolerated, or contraindicated; and

·      Oral therapy with hydroxyurea or other myelosuppressive agent is not effective, not tolerated, or is contraindicated.

Failure of phlebotomy and/or myelosuppressive agents is defined as any of the following:

·      Lack of hematological control (e.g., hematocrit greater than 45 or platelet count greater than 600 x 109/L);

·      Phlebotomy required more often than once every two months;

·      Occurrence of thrombotic or hemorrhagic complications;

·      Occurrence of intractable symptoms (e.g., headaches, pruritus);

·      Occurrence of symptoms related to hepatosplenomegaly.

2)    Malignant mesothelioma in persons who have relapsed following surgery and failed treatment with or cannot tolerate first-line chemotherapy;

3)    Hepatitis C (non-A, non-B hepatitis), in compensated liver disease manifest by the following:

·      Laboratory parameters are all within the following ranges:

a.  bilirubin less than 2 mg/dL;

b.  albumin stable and within normal limits;

c.  INR less than 3;

d.  WBC greater than 3000/mm3;

e.  platelets greater than 70,000/mm3;

f.   serum creatinine normal or near normal

·      No history of hepatic encephalopathy, variceal bleeding, ascites, or other clinical signs of decompensation.

4)    Persons with chronic hepatitis B who meet all of the following criteria:

·      Serum aminotransferase (AST) greater than double the upper limit of normal range (AST normal range 0-35 u/l);

·      Member has compensated liver disease manifest by the following:

a.  Bilirubin less than 2mg/dL;

b.  Albumin stable and within normal limits;

c.  PT less than 3 seconds prolonged or INR less than 2;

d.  WBC greater than 3000/mm3;

e.  Platelets greater than 70,000/mm3;

f.   Serum creatinine normal or near normal).

g.  No history of hepatic encephalopathy, variceal bleeding, ascites, or other clinical signs of decompensation;

II.  PEGylated Interferon Alpha (requires pre-authorization)

A.   Pegasys (PEGylated interferon alfa-2a) is considered medically necessary, either as monotherapy or in combination with ribavirin (Rebetol), for the treatment of chronic hepatitis C in persons who are interferon naïve or who have relapsed or failed to respond to prior non-PEGylated interferon therapy with compensated liver disease manifest by:

1)    Bilirubin less than 2 mg/dL;

2)    Albumin stable and within normal limits;

3)    PT less than 3 seconds prolonged or INR less than 2;

4)    WBC greater than 3000/mm3;

5)    Platelets greater than 70,000/mm3;

6)    Serum creatinine normal or near normal

7)    No history of hepatic encephalopathy, variceal bleeding, ascites, or other clinical signs of decompensation.

B.  Peginterferon alfa-2a (Pegasys) is considered medically necessary for the treatment of adult persons with HBeAg positive or HBeAg negative chronic hepatitis B who have compensated liver disease manifest by:

1)    Bilirubin less than 2mg/dL;

2)    Albumin stable and within normal limits;

3)    PT less than 3 seconds prolonged or INR less than 2;

4)    WBC greater than 3000/mm3;

5)    Platelets greater than 70,000/mm3;

6)    Serum creatinine concentrations less than 1.5 times upper limit of normal;

7)    No history of hepatic encephalopathy, variceal bleeding, ascites, or other clinical signs of decompensation;

8)    Evidence of viral replication (HBV greater than 500,000 copies per ml for HBeAg positive and HBV greater than 100, 000 copies per ml for HBeAg negative)

9)    Liver inflammation (serum aminotransferase (AST) greater than the upper limit of normal range (AST normal range 0-35 u/l));

10)   Who are interferon naïve or who have relapsed or failed to respond to prior non-PEGylated interferon therapy?

C. Pegylated interferon alfa-2b is considered medically necessary for patients who meet the following criteria:

1)  Diagnosis of melanoma with microscopic or gross nodal involvement AND

2)  Medication will be used as adjuvant therapy within 84 days of definitive surgical resection AND

        3)  Patient does not have the following contraindications:

     a. Autoimmune hepatitis

     b. Hepatic decompensation (Child-Pugh score higher than 6 [class B or C]

III.  Consensus Interferon (Interferon alfacon-1) (requires pre-authorization)

A.   Consensus interferon (Infergen interferon alfacon-1) is considered medically necessary for treatment of chronic hepatitis C in persons with compensated liver disease who meet medical necessity criteria for interferon alpha.

IV.      Interferon beta requires pre-authorization

Interferon beta-1a (Avonex, Rebif) or interferon beta-1b (Betaseron) are considered medically necessary for the treatment of relapsing/remitting multiple sclerosis in members who meet the following criteria for either clinically definite or laboratory supported definite MS:

1)  Clinically definite MS is defined as either:

·   Two attacks and clinical evidence of two separate lesions; or

·   Two attacks; clinical evidence of one lesion and para-clinical evidence of another, separate lesion

2)  Laboratory-supported definite MS consists of demonstration of any of the following:

·   Two attacks; either clinical or para-clinical evidence of one lesion; and CSF OB/IgG*; or

·   One attack; clinical evidence of two separate lesions; and CSF OB/IgG*; or

·   One attack; clinical evidence of one lesion and para-clinical evidence of another separate lesion; and CSF OB/IgG

§ CSF OB/IgG is defined as either:

·   IgG oligoclonal band (OB) in the CSF (Oligoclonal bands must not be present in the member`s serum and the serum IgG level must be normal); or

·   Increased CNS synthesis of IgG (IgG is higher in CSF than in serum, and is increased in the CSF in the presence of a normal concentration of total protein).

·   Single attack with MRI evidence for Multiple Sclerosis (Clinically Isolated Syndrome). See MS Policy

V.  PEGylated Interferon Beta-1a

PEGylated Interferon Beta 1-a (Plegridy) is considered medically necessary for the treatment of relapsing/remitting multiple sclerosis in members who meet the following criteria for either clinically definite or laboratory supported definite MS:

1) Clinically definite MS is defined as either:

·   Two attacks and clinical evidence of two separate lesions; or

·   Two attacks; clinical evidence of one lesion and para-clinical evidence of another, separate lesion

2) Laboratory-supported definite MS consists of demonstration of any of the following:

·   Two attacks; either clinical or para-clinical evidence of one lesion; and CSF OB/IgG*; or

·   One attack; clinical evidence of two separate lesions; and CSF OB/IgG*; or

·   One attack; clinical evidence of one lesion and para-clinical evidence of another separate lesion; and CSF OB/IgG

o  CSF OB/IgG is defined as either:

·   IgG oligoclonal band (OB) in the CSF(Oligoclonal bands must not be present in the member`s serum and the serum IgG level must be normal); or

·   Increased CNS synthesis of IgG (IgG is higher in CSF than in serum, and is increased in the CSF in the presence of a normal concentration of total protein).

·   Single attack with MRI evidence for Multiple Sclerosis (Clinically Isolated Syndrome). See MS Policy

VI. Interferon Gamma 1-B

Interferon Gamma 1 is considered medically necessary for the following indications (for these indications, no pre-authorization is required. For all other indications, payment will be denied):

1)    Chronic granulomatous disease, to reduce the frequency and severity of infections;

2)    Chronic recalcitrant atopic dermatitis;

3)    Idiopathic pulmonary fibrosis;

4)    Waldenstrom`s Macroglobulinemia.

Codes Used In This BI:

J1830   Interferon Beta-1B 0.25mg SC (Betaseron)

J9212   Interferon alfacon-1, 1 mcg (Infergen)

J9213   Interferon alpha-2A, 3 million units (Roferon-A)

J9214   Interferon alpha-2B, 1 million units (Intron A)

J9215   Interferon alfa-n3 inj

J9216   Interferon gamma 1-b inj

S0145   Peginterferon alpha-2A (Pegasys)

Interferon Alpha:

Continued treatment with interferon alpha is considered not medically necessary for persons with HCV genotypes 1 and 4 who have failed to attain an early virologic response after 12 weeks of treatment (where early virologic response is indicated by achievement of at least a 100-fold (2 log10) decrease in serum HCV from pretreatment baseline).

Up to a maximum of 24 weeks of interferon alpha is considered medically necessary for persons with HCV genotypes 2 and 3, and up to a maximum of 48 weeks of interferon alpha is considered medically necessary for persons with HCV genotypes 1 and 4.

Extended treatment with interferon alpha beyond these limits will be considered medically necessary for persons with cryoglobulinemia and for liver transplant recipients with recurrent hepatitis C infection.

A course of standard interferon alpha in persons with hepatitis C who have failed an adequate course of PEGylated interferon alpha is considered experimental and investigational because of a lack of evidence on the effectiveness of standard interferon in these persons.

The use of interferon alpha is considered contraindicated in the following persons with hepatitis B:

·       Those who are HIV positive;

·       Hepatitis B surface antigen (HBs Ag) positive persons undergoing liver transplantation;

·       Those with a history of or currently active autoimmune hepatitis.

A course of standard interferon alpha in persons with hepatitis B who have failed an adequate course of PEGylated interferon alpha is considered experimental and investigational because of a lack of evidence on the effectiveness of standard interferon in these persons.

Interferon alpha is considered experimental and investigational for all other indications because it has not been shown to be effective for them including:

1.          Acute hepatitis B;

2.          Age-related macular degeneration;

3.          AIDS-related complex;

4.          AIDS in combination with AZT;

5.          Breast cancer;

6.          Chickenpox;

7.          Chronic delta hepatitis;

8.          Cutaneous warts;

9.          Cytomegalovirus (CMV);

10.      Gardner syndrome;

11.      Hepatitis D;

12.      Hereditary hemorrhagic telangiectasia;

13.      Herpes keratoconjunctivitis;

14.      Herpes simplex;

15.      Keloids;

16.      Multiple sclerosis

17.      Peyronie`s disease

18.      Plexiform neurofibroma;

19.      Rhinoviruses;

20.      Vaccinia; and

21.      Varicella zoster virus (VZV).

PEGylated Interferon Alpha:

PEGylated interferon alpha 2B (Peg Intron) is not covered for treatment of Hepatitis C.

Continued treatment with PEGylated interferon alpha is considered not medically necessary for persons with HCV genotypes 1 and 4 who have failed to attain an early virologic response after 12 weeks of therapy.
Early virologic response is indicated by achievement of at least a 100-fold (2 log10) decrease in serum HCV RNA from pretreatment baseline.

For persons infected with HCV genotypes 1 and 4, up to 48 weeks of treatment with PEGylated interferons is considered medically necessary.

For persons with other HCV genotypes (i.e., genotypes 2 and 3, and genotypes 5 through 10) up to 24 weeks of treatment with PEGylated interferons are considered medically necessary.

Repeat or chronic maintenance treatment with PEGylated interferon (PEG-Intron or Pegasys) is considered not medically necessary in persons who have completed a therapeutic course of PEGylated interferon and ribavirin.

Extended treatment with PEGylated interferon alpha beyond these limits will be considered medically necessary for persons with cryglobulinemia and for liver transplant recipients with recurrent hepatitis C infections.

Treatment with peginterferon alfa-2a for more than 48 weeks is considered experimental and investigational.

Repeat or chronic maintenance treatment with peginterferon alfa-2a is considered not medically necessary in persons who have completed a therapeutic course of PEGylated interferon and ribavirin.

Extended treatment with peginterferon alfa-2a beyond these limits will be considered medically necessary for liver transplant recipients with recurrent hepatitis B infections.

PEGylated interferons are self-administered subcutaneously once weekly.

Consensus Interferon (Interferon Alfacon-1):

Use of consensus interferon for persons with hepatitis C who fail to respond to standard alpha interferon or PEGylated interferons is considered experimental and investigational. Current guidelines indicate PEGylated interferons as the treatment of choice for persons with hepatitis C, including those who fail to respond to standard alpha interferon therapy.
There is insufficient evidence in the peer-reviewed published medical literature comparing consensus interferon to PEGylated interferons, and of the effectiveness of consensus interferon in persons with hepatitis C who have failed PEGylated interferon therapy.

Interferon Beta:

Because interferon beta is administered subcutaneously or intramuscularly, it is appropriate for administration by the member in the home setting.

The Biojector 2000 (Bioject, Inc.) is a needle-free injection system that uses CO2 as the power source and disposable needle-free syringes to deliver medication in a fraction of a second through a tiny orifice. Biojector 2000 is considered an acceptable alternative to conventional needle and syringes for members with exacerbating-remitting MS who cannot safely use needles for self-injection due to tremors and decreased coordination.

Interferon Gamma:

Interferon gamma is considered experimental and investigational for the treatment of malignant neoplasm of peritoneum.

1)    Ziesche R, Hofbauer E, Wittmann K, et al. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 1999;341(17):1264-1269.

2)    Hadziyannis SJ, Papatheodoridis GV. Peginterferon-a2a (40 kDa) for chronic hepatitis C. Expert Opin Pharmacother. 2003;4(4):541-551.

3)    Herrine SK, Brown R Jr, Esposito S, et al. Efficacy and safety of peginterferon a2a (Pegasys) combination therapies in patients with chronic hepatitis C (CHC) who relapsed on interferon a2b plus ribavirin (Rebetron) therapy [abstract]. Hepatology. 2002;36:358A.

4)    Cooksley WG, Piratvisuth T, Lee SD, et al. Peginterferon alpha-2a (40 kDa): An advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat. 2003;10(4):298-305.

5)    Hauschild A, Weichenthal M, Balda BR, et al. Prospective randomized trial of interferon alpha-2b and interleukin-2 as adjuvant treatment for resected intermediate- and high-risk primary melanoma without clinically detectable node metastasis. J Clin Oncol. 2003;21(15):2883-2888.

6)    National Institute for Clinical Excellence (NICE). Interferon alpha (PEGylated and non-PEGylated) and ribavirin for the treatment of chronic hepatitis C. Technology Appraisal 75. London, UK: NICE; January 2004. Available at: http://www.nice.org.uk/page.aspx?o=102243 .

7)    Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: A randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140(5):346-355.

8)    Hancock BW, Wheatley K, Harris S, et al. Adjuvant interferon in high-risk melanoma: The AIM HIGH Study--United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma. J Clin Oncol. 2004;22(1):53-61.

9)    Kleeberg UR, Suciu S, Brocker EB, et al. Final results of the EORTC 18871/DKG 80-1 randomized phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis. Eur J Cancer. 2004;40(3):390-402.

10)   Rotoli B, De Renzo A, Frigeri F, et al. A phase II trial on alpha-interferon (alpha IFN) effect in patients with monoclonal IgM gammopathy. Leuk Lymphoma. 1994;13(5-6):463-469.

11)   Legouffe E, Rossi JF, Laporte JP, et al. Treatment of Waldenstrom`s Macroglobulinemia with very low doses of alpha interferon. Leuk Lymphoma. 1995;19(3-4):337-342.

12)   Vela-Ojeda J, Garcia-Ruiz Esparza MA, Padilla-Gonzalez Y, et al. IFN-alpha as induction and maintenance treatment of patients newly diagnosed with Waldenstrom`s Macroglobulinemia. J Interferon Cytokine Res. 2002;22(10):1013-1016.

13)   Brake M, Loertzer H, Horsch R, Keller H. Treatment of Peyronie`s disease with local interferon-alpha 2b. BJU Int. 2001;87(7):654-657.

14)   Lacy GL 2nd, Adams DM, Hellstrom WJ. Intralesional interferon-alpha-2b for the treatment of Peyronie`s disease. Int J Impot Res. 2002;14(5):336-339.

15)   Dang G, Matern R, Bivalacqua TJ, et al. Intralesional interferon-alpha-2B injections for the treatment of Peyronie`s disease. South Med J. 2004;97(1):42-46.

16)   National Institutes of Health (NIH). Management of hepatitis C: 2002. Rockville, MD: NIH; August 26, 2002.

17)   Plegridy prescribing information. Biogen Idec Inc. August 2014.

18)   Sylatron Prescribing Information. Schering Corporation. Kenilworth, NJ. March 2011.