Peginterferon alfa-2b

Last updated
Peginterferon alfa-2b
Clinical data
Trade names PegIntron, Sylatron, ViraferonPeg, others
AHFS/Drugs.com Professional Drug Facts
MedlinePlus a605030
Routes of
administration 		Subcutaneous injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life 22–60 hrs
Identifiers
  • PEGylated human interferon alpha 2b
CAS Number
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
ECHA InfoCard 100.208.164 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C860H1353N229O255S9
Molar mass 19269.17 g·mol−1
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Pegylated interferon alfa-2b is a drug used to treat melanoma, as an adjuvant therapy to surgery. [3] Also used to treat hepatitis C (typically, in combination with ribavarin), it is no longer recommended due to poor efficacy and adverse side-effects. [4] Subcutaneous injection is the preferred delivery method. [3]

Contents

Belonging to the alpha interferon family of medications, the molecule is PEGylated to prevent breakdown. [3] [4] Approval for medical use in the United States was granted in 2001. [3] It is on the World Health Organization's List of Essential Medicines as a therapy for chronic hepatitis C. [5] [6]

Medical uses

Hepatitis

Till around 2010, PEGylated interferon alfa-2b in combination with ribavirin, was part of the standard regimen used in management of hepatitis C. [4] [7] Ribivarin helped in increasing the Sustained Virologic Response (SVR) even more. [8] Developed by Schering-Plough, the drug was approved by Food and Drug Administration (FDA) of the United States in 2001, and has been on the World Health Organization's List of Essential Medicines as a therapy for chronic hepatitis C since 2013. [4] [5] [6]

A 2013 meta-analysis over Clinical Infectious Diseases noted the combination-treatment to be safe as well as effective for children and adolescents; other meta-analyses had noted the same for adult population. [9] A 2012 meta-analysis had found PEGylated interferon alfa-2a to be the more effective variant for treatment-naive patients. [10]

With the advent of Direct-Acting-Antivirals (DAAs — ), interferon-based treatment regimens gradually fell out of fashion due to relatively poor efficacy and high frequency of adverse side-effects. [4] [7] [11] No longer recommended, the use of PEGylated interferon alfa-2b has essentially ceased in all countries, where DAA therapeutics are available. [12] [4]

Melanoma

For high-risk melanoma, it is used as an adjuvant therapy to surgery in some countries. [3] [13] It was first approved for the purpose by FDA on March 29, 2011, based on a single phase III trial. [14] [15]

The usage remains controversial — frequency of severe side-effects is high, overall survival benefits substantially vary across different trials, and there is no consensus on the dosage regimen. [16] Meta-analyses have suggested that the drug might be more helpful for patients with ulcerated primary lesion. [16]

COVID-19

On 23 April 2021, the Drugs Controller General of India approved emergency use of the medication (upon a request by Cadila Healthcare; trade name is Virafin) for treating moderate COVID-19 infections. [17] No publication (or preprint) yet exists; the phase II trial was poorly designed and not robust. [17]

Side effects

Adverse side effects are common and often require dose reduction or outright discontinuation. [4] [8]

Common side effects include fatigue, headache, insomnia, depression, mood swings, hair loss, nausea, diarrhea, myalgia and associated skeletal pain, anorexia, fever etc. [3] [4] Relatively rare effects include imbalance of thyroid hormones, xerostomia, thrombocytopenia, hepatomegaly, pharyngitis, cough, psychosis, rashes, arrythmia, anemia etc. [3] Severe side effects may include a range of potentially fatal neuropsychiatric, autoimmune, ischemic, or infectious disorders. [3] [4]

Mechanism of action

Host genetic factors

For genotype 1 hepatitis C treated with pegylated interferon-alfa-2a or pegylated interferon-alfa-2b combined with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in response to the treatment. This finding, originally reported in Nature, [18] showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more likely to achieve sustained virological response after the treatment than others. A later report from Nature [19] demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus.

Related Research Articles

<span class="mw-page-title-main">Interferon</span> Signaling proteins released by host cells in response to the presence of pathogens

Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

<span class="mw-page-title-main">Ribavirin</span> Antiviral medication

Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. Among the viral hemorrhagic fevers it is sometimes used for Lassa fever, Crimean–Congo hemorrhagic fever, and Hantavirus infection but should not be used for Ebola or Marburg infections. Ribavirin is taken orally or inhaled. Despite widespread usage, since the 2010s it has faced scrutiny for a lack of efficacy in treating viral infections it has historically been prescribed for.

Pegylated interferon alfa-2a, sold under the brand name Pegasys among others, is medication used to treat hepatitis C and hepatitis B. For hepatitis C it is typically used together with ribavirin and cure rates are between 24 and 92%. For hepatitis B it may be used alone. It is given by injection under the skin.

Pegylated interferon (PEG-IFN) is a class of medication that includes three different drugs as of 2012:

<span class="mw-page-title-main">Interferon type I</span> Cytokine

The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cytoband over approximately 400 kb including coding genes for IFNα, IFNω (IFNW1), IFNɛ (IFNE), IFNк (IFNK) and IFNβ (IFNB1), plus 11 IFN pseudogenes.

Interferon alfa-2b is an antiviral or antineoplastic drug. It is a recombinant form of the protein Interferon alpha-2 that was originally sequenced and produced recombinantly in E. coli in the laboratory of Charles Weissmann at the University of Zurich, in 1980. It was developed at Biogen, and ultimately marketed by Schering-Plough under the trade name Intron-A. It was also produced in 1986 in recombinant human form, in the Center for Genetic Engineering and Biotechnology of Havana, Cuba, under the name Heberon Alfa R.

<span class="mw-page-title-main">Boceprevir</span> Chemical compound

Boceprevir is a protease inhibitor used to treat hepatitis caused by hepatitis C virus (HCV) genotype 1. It binds to the HCV nonstructural protein 3 active site.

<span class="mw-page-title-main">Telaprevir</span> Chemical compound

Telaprevir (VX-950), marketed under the brand names Incivek and Incivo, is a pharmaceutical drug for the treatment of hepatitis C co-developed by Vertex Pharmaceuticals and Johnson & Johnson. It is a member of a class of antiviral drugs known as protease inhibitors. Specifically, telaprevir inhibits the hepatitis C viral enzyme NS3/4A serine protease. Telaprevir is only indicated for use against hepatitis C genotype 1 viral infections and has not been proven to be safe or effective when used for other genotypes of the virus. The standard therapy of pegylated interferon and ribavirin is less effective than telaprevir in those with genotype 1.

<span class="mw-page-title-main">Alisporivir</span> Chemical compound

Alisporivir (INN), or Debio 025, DEB025, is a cyclophilin inhibitor. Its structure is reminiscent of, and synthesized from ciclosporin.

WGAViewer is a bioinformatics software tool which is designed to visualize, annotate, and help interpret the results generated from a genome wide association study (GWAS). Alongside the P values of association, WGAViewer allows a researcher to visualize and consider other supporting evidence, such as the genomic context of the SNP, linkage disequilibrium (LD) with ungenotyped SNPs, gene expression database, and the evidence from other GWAS projects, when determining the potential importance of an individual SNP.

<span class="mw-page-title-main">Sofosbuvir</span> Chemical compound

Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken by mouth.

<span class="mw-page-title-main">Interferon Lambda 3</span> Protein-coding gene in the species Homo sapiens

Interferon lambda 3 encodes the IFNL3 protein. IFNL3 was formerly named IL28B, but the Human Genome Organization Gene Nomenclature Committee renamed this gene in 2013 while assigning a name to the then newly discovered IFNL4 gene. Together with IFNL1 and IFNL2, these genes lie in a cluster on chromosomal region 19q13. IFNL3 shares ~96% amino-acid identity with IFNL2, ~80% identity with IFNL1 and ~30% identity with IFNL4.

<span class="mw-page-title-main">Simeprevir</span> Chemical compound

Simeprevir, sold under the brand name Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with include sofosbuvir or ribavirin and peginterferon-alfa. Cure rates are in 80s to 90s percent. It may be used in those who also have HIV/AIDS. It is taken by mouth once daily for typically 12 weeks.

<span class="mw-page-title-main">Beclabuvir</span> Chemical compound

Beclabuvir is an antiviral drug for the treatment of hepatitis C virus (HCV) infection that has been studied in clinical trials. In February 2017, Bristol-Myers Squibb began sponsoring a post-marketing trial of beclabuvir, in combination with asunaprevir and daclatasvir, to study the combination's safety profile with regard to liver function. From February 2014 to November 2016, a phase II clinical trial was conducted on the combination of asunaprevir/daclatasvir/beclabuvir on patients infected with both HIV and HCV. Furthermore, a recent meta-analysis of six published six clinical trials showed high response rates in HCV genotype 1-infected patients treated with daclatasvir, asunaprevir, and beclabuvir irrespective of ribavirin use, prior interferon-based therapy, or restriction on noncirrhotic patients, IL28B genotype, or baseline resistance-associated variants

Elbasvir/grazoprevir, sold under the brand name Zepatier, is a fixed-dose combination for the treatment of hepatitis C, containing elbasvir and grazoprevir. It is used to treat chronic hepatitis C virus (HCV) genotypes 1 or 4 infection in both treatment-naïve and treatment-experienced patients.

<span class="mw-page-title-main">Narlaprevir</span> Chemical compound

Narlaprevir, is an inhibitor of NS3/4A serine protease, intended for the treatment of chronic hepatitis C caused by genotype 1 virus in combination with other antiviral drugs.

<span class="mw-page-title-main">NS5B inhibitor</span> Class of pharmaceutical drugs

Non-structural protein 5B (NS5B) inhibitors are a class of direct-acting antivirals widely used in the treatment of chronic hepatitis C. Depending on site of action and chemical composition, NS5B inhibitors may be categorized into three classes—nucleoside active site inhibitors (NIs), non-nucleoside allosteric inhibitors, and pyrophosphate analogues. Subsequently, all three classes are then subclassified. All inhibit RNA synthesis by NS5B but at different stages/sites resulting in inability of viral RNA replication. Expression of direct-acting NS5B inhibitors does not take place in cells that are not infected by hepatitis C virus, which seems to be beneficial for this class of drugs.

The term Direct-acting antivirals (DAA) has long been associated with the combination of antiviral drugs used to treat hepatitis C infections. These are the more effective than older treatments such as ribavirin and interferon. The DAA drugs against hepatitis C are taken orally, as tablets, for 8 to 12 weeks. The treatment depends on the type or types (genotypes) of hepatitis C virus that are causing the infection. Both during and at the end of treatment, blood tests are used to monitor the effectiveness of the treatment and subsequent cure.

<span class="mw-page-title-main">Interferon Lambda 4</span> Protein-coding gene in the species Homo sapiens

Interferon lambda 4 is one of the most recently discovered human genes and the newest addition to the interferon lambda protein family. This gene encodes the IFNL4 protein, which is involved in immune response to viral infection.

Merimepodib (VX-497) is a drug which acts as an inhibitor of the enzyme inosine monophosphate dehydrogenase, which is required for the synthesis of nucleotide bases containing guanine. This consequently inhibits synthesis of DNA and RNA, and results in antiviral and immunosuppressive effects. It progressed as far as Phase 2b human clinical trials against Hepatitis C but showed only modest benefits in comparison to existing treatments, however it continues to be researched, and also shows activity against other viral diseases such as Zika virus and foot and mouth disease virus.

References

  1. ↑ "PegIntron- peginterferon alfa-2b injection, powder, lyophilized, for solution PegIntron- peginterferon alfa-2b kit". DailyMed. Retrieved 28 September 2020.
  2. ↑ "Sylatron- peginterferon alfa-2b kit". DailyMed. 28 August 2019. Retrieved 28 September 2020.
  3. 1 2 3 4 5 6 7 8 "Peginterferon Alfa-2b (Professional Patient Advice) - Drugs.com". www.drugs.com. Archived from the original on 16 January 2017. Retrieved 12 January 2017.
  4. 1 2 3 4 5 6 7 8 9 "Peginterferon alfa-2b (PegIntron)". Hepatitis C Online. Infectious Diseases Education & Assessment, University of Washington. January 2021. Retrieved 12 January 2017.
  5. 1 2 World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. 1 2 "eEML - Electronic Essential Medicines List". list.essentialmeds.org. Retrieved 2021-05-21.
  7. 1 2 Hsu CS, Chao YC, Lin HH, Chen DS, Kao JH (May 2015). "Systematic Review: Impact of Interferon-based Therapy on HCV-related Hepatocellular Carcinoma". Scientific Reports. 5 (1): 9954. doi:10.1038/srep09954. PMC   4428066 . PMID   25963067.
  8. 1 2 The Selection and Use of Essential Medicines: Report of the WHO Expert Committee (PDF). WHO Technical Report Series: 985. Geneva: World Health Organization. 2013. p. 42.
  9. ↑ Druyts E, Thorlund K, Wu P, Kanters S, Yaya S, Cooper CL, Mills EJ (April 2013). "Efficacy and safety of pegylated interferon alfa-2a or alfa-2b plus ribavirin for the treatment of chronic hepatitis C in children and adolescents: a systematic review and meta-analysis". Clinical Infectious Diseases. 56 (7): 961–7. doi: 10.1093/cid/cis1031 . PMID   23243171.
  10. ↑ Singal AK, Jampana SC, Anand BS (August 2011). "Peginterferon alfa-2a is superior to peginterferon alfa-2b in the treatment of naïve patients with hepatitis C virus infection: meta-analysis of randomized controlled trials". Digestive Diseases and Sciences. 56 (8): 2221–6. doi:10.1007/s10620-011-1765-0. PMID   21643737. S2CID   34328390.
  11. ↑ Pockros PJ. "Direct-acting antivirals for the treatment of hepatitis C virus infection". UpToDate . Retrieved 2021-05-21.
  12. ↑ Spengler U (March 2018). "Direct antiviral agents (DAAs) - A new age in the treatment of hepatitis C virus infection". Pharmacology & Therapeutics. 183: 118–126. doi:10.1016/j.pharmthera.2017.10.009. PMID   29024739. S2CID   3337006.
  13. ↑ Di Trolio R, Simeone E, Di Lorenzo G, Grimaldi AM, Romano A, Ayala F, et al. (September 2012). "Update on PEG-interferon α-2b as adjuvant therapy in melanoma". Anticancer Research. 32 (9): 3901–9. PMID   22993335.
  14. ↑ Herndon TM, Demko SG, Jiang X, He K, Gootenberg JE, Cohen MH, et al. (2012). "U.S. Food and Drug Administration Approval: peginterferon-alfa-2b for the adjuvant treatment of patients with melanoma". The Oncologist (in Chinese). 17 (10): 1323–8. doi:10.1634/theoncologist.2012-0123. PMC   3481898 . PMID   23002124.
  15. ↑ Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, et al. (July 2008). "Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial" (PDF). Lancet. 372 (9633): 117–26. doi:10.1016/S0140-6736(08)61033-8. PMID   18620949. S2CID   665063.
  16. 1 2 Trinh VA, Zobniw C, Hwu WJ (August 2017). "The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma". Expert Opinion on Drug Safety. 16 (8): 933–940. doi:10.1080/14740338.2017.1343301. PMID   28627943. S2CID   22139797.
  17. 1 2 Borana R (2021-04-24). "DCGI Approves Virafin for Moderate COVID. Where's the Evidence It Works?". The Wire Science. Retrieved 2021-05-20.
  18. ↑ Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. (September 2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature. 461 (7262): 399–401. Bibcode:2009Natur.461..399G. doi:10.1038/nature08309. PMID   19684573. S2CID   1707096.
  19. ↑ Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O'Huigin C, et al. (October 2009). "Genetic variation in IL28B and spontaneous clearance of hepatitis C virus". Nature. 461 (7265): 798–801. Bibcode:2009Natur.461..798T. doi:10.1038/nature08463. PMC   3172006 . PMID   19759533.
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