Interferon therapy

Interferons. Table 1 Approved indications for interferon therapy either as adjuvant or for monotherapy... 

Gunsar E, Akarca US, Ersoz G, Kobak AC, Karasu Z, Yuce G, liter T, Batur Y (2005) Two-year interferon therapy with or without ribavirin in chronic delta hepatitis. Antivir Ther 10 721-726 Habersetzer E, Boyer N, MarceUin P, Badly F, Ahmed SN, Alam J, Benhamou JP, Trepo C (2000) A pdot study of recombinant interferon beta-la for the treatment of chronic hepatitis C. Liver 20 437 41... 

Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, Liaw YE (2007) Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol 46 45-52... 

Interferon alfa is an antiviral agent that is effective in suppressing hepatitis B viral replication. Interferon alfa-2b and pegylated interferon alfa-2a are the only interferon therapies approved for the treatment of chronic hepatitis B. 

Factors associated with a higher likelihood of response to interferon therapy are baseline HBV DNA levels less than 200 pg/mL and ALT concentrations greater than 5 times the upper limit of normal.29... 

Neutropenia associated with interferon or pegylated interferon therapy is defined as an absolute neutrophil count (ANC) of less than 1000 cells/mm3 in rare cases, an ANC less than 500 cells/mm3 maybe observed. The neutropenia is more common and in some cases more severe with pegylated interferon than with unmodified interferon. Neutropenia usually occurs within the first 2 weeks after initiating either formulation of interferon, with the WBC count stabilizing by week four or six. The neutropenia is reversible upon discontinuing therapy. Granulocyte colony-stimulating factor has been used as an adjunctive therapy for interferon-induced neutropenia in hepatitis patients.44... 

While there are no FDA-approved treatments for hepatitis D, interferon has been shown to be effective.46 48 Various doses have been evaluated, with the most effective treatment being 9 million units three times weekly.47 Seventy-one percent of patients who were treated with this regimen for 48 weeks had normalized ALT levels.47 Adverse effects and monitoring parameters for interferon therapy are similar to treatment for hepatitis C. In some situations, patients infected with hepatitis D who develop hepatic decompensation and ESLD may need to undergo liver transplantation. 

Carreno, V., et al. (1992). Long-term follow-up of hepatitis B chronic carriers who responded to interferon therapy. J. Hepatol. 15, 102-106. 

McHutchinson, J. G., etal. (1997). Hepatitis C and G co-infection Response to interferon therapy and quantitative changes in serum HGV-RNA. Hepatology 26, 1322-1327. 

Reder, A. 1996. Interferon Therapy of Multiple Sclerosis. Marcel Dekker. 

Tossing, G. 2001. New developments in interferon therapy. European Journal of Medical Research 6(2), 47-65. Veronese, F.M. and Pasut, G. 2005. PEGylation, successful approach to drug delivery. Drug Discovery Today 10, 1451-1458. 

Wandl, U.B. et al., Lupus-like autoimmune disease induced by interferon therapy for myeloproliferative disorders, Clin. Immunol. Immunopathol., 65, 70, 1992. 

Chronic HCV- In combination with interferon alfa-2b injection for the treatment of chronic HCV in patients 3 years of age (oral solution) or 5 years of age (capsules) and older with compensated liver disease previously untreated with alpha interferon or in patients who have relapsed following alpha interferon therapy. Note Ribaspheres is only indicated in combination with interferon alfa-2b in patients 18 years of age and older. 

Therapy relapse - In patients who relapse following interferon therapy, the recommended duration of treatment is 24 weeks. There are no safety and efficacy data on treatment for more than 24 weeks in the relapse patient population. 

Puimonary disorders Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, and sarcoidosis, some resulting in respiratory failure and/or patient deaths, may be induced or aggravated by peginterferon alfa-2a or alpha interferon therapy. 

Hypersensitivity reactions Serious, acute hypersensitivity reactions (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis) have been rarely observed during alpha interferon therapy. 

The most frequent adverse effects are flu-like symptoms increased body temperature, feeling ill, fatigue, headache, muscle pain, convulsion, dizziness, hair thinning and depression. Erythema, pain and hardness on the spot of injection are also frequently observed. Interferon therapy may cause immunosuppression. Also various interferon induced autoimmune syndromes were reported. 

Surgery remains the mainstay of treatment for localized disease. Approximately 30% of patients present with metastatic disease. Although nephrectomy has traditionally not been recommended in the context of metastatic disease, except in cases of pain or hemorrhage due to local tumor burden, two recent phase III studies have reported modest improvement in durations of survival when carefully selected patients undergo nephrectomy followed by interferon therapy. The larger of the two studies reported a median survival advantage of 3 months. 

Flulike symptoms, including fever, chills, weakness, fatigue, myalgia, and arthralgia, are the most common side effects of interferon therapy. These symptoms occur in more than 50% of patients given injections of interferons either intravenously, intramuscularly, or subcutaneously. Intralesional injection may produce milder flulike symptoms with somewhat less frequency. Tolerance to these symptoms generally develops with repeated dosing. 

Infrequent reactions to interferon therapy include proteinuria, renal toxicity, autoimmune disease, thyroid disease, ophthalmic toxicity, pulmonary dysfunction (pulmonary infiltrates, pneumonitis, and pneumonia), and cardiovascular effects (tachycardia, arrhythmia, hypotension, cardiomyopathy, and myocardial infarction). Rarely, the body may develop antibodies against interferons that inhibit their effectiveness. 

Although ribavirin monotherapy is ineffective against HCV, oral ribavirin in combination with inter-feron-a (Rebatron) is approved for this indication and is effective in patients resistant to interferon therapy alone. Intravenous ribavirin may be useful in the therapy of Hantaan virus infection, Crimean or Congo virus hemorrhagic fever, Lassa fever, and severe adenovirus infection. 

Interferon therapy should be used with great caution in patients with decompensated cirrhosis since treatment may flare their disease, resulting in hepatic failure, and is often associated with significant cytopenia or infection [30,31]. Other ab-... 

Alexander, G.J.M., J. Brahm, E.A. Eagan, et al.. Loss of HBsAg with interferon therapy... 

Di Bisceglie, A.M.,T.L. Fong, M.W. Fried, et al., A randomized controlled trial of recombinant alpha-interferon therapy for chronic hepatitis B. Am 1 Gastroenterol, 1993. 88 1887-92. 

Brook, M.G., P. Karayiannis, and H.C. Thomas, Which patients with chronic hepatitis B virus infection will respond to alpha-interferon therapy A statistical analysis of predictive factors. Hepatology, 1989. 10 761-63. 

Shindo, M., A.M. Di Bisceglie, L. Cheung, et al.. Decrease in serum hepatitis C viral RNA during alpha-interferon therapy for chronic hepatitis C. Ann Intern Med,1991.115 700-4. 

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