What is the Difference Between Peginterferon Alfa 2A and 2B

The main difference between peginterferon alfa 2a and 2b is the structure of the polyethylene glycol (PEG) chain and the effect due to it. That is; peginterferon-alfa-2a (PEG-IFN alfa-2a) contains a branched, 40 kDa PEG chain. And, this chain is covalently attached via stable amide bonds to the lysine residues of interferon-alpha-2a and hence, circulates as an intact molecule. But, peginterferon-alfa-2b (PEG-IFN alfa-2b) contains a linear, 12 kDa PEG chain. In this, the chain is covalently attached, primarily, to histidine-34 of interferon-alpha-2b via an unstable urethane bond, which is subjected to hydrolysis once injected, and thus, releasing native interferon-alpha-2b.

Peginterferon-alfa-2a and -2b are the two types of pegylated interferons widely available for the treatment of chronic hepatitis C (HCV) infection. However, peginterferon-alpha-2a has a very restricted volume of distribution, longer half-life, and reduced clearance, and hence, it can be given once weekly, independent of the body weight. But, peginterferon-alpha-2b has a shorter half-life in serum and hence, it requires body weight-based dosing. Furthermore, peginterferon-alfa-2a has a relatively constant absorption and is mostly distributed in the blood and organs, while peginterferon-alfa-2b has both a rapid absorption and a wider distribution in the body. 

Key Areas Covered 

1. What is Peginterferon Alfa 2A
     – Definition, Structure, Properties
2. What is Peginterferon Alfa 2B
     – Definition, Structure, Properties
3. What are the Similarities Between Peginterferon Alfa 2A and 2B
     – Outline of Common Features
4. What is the Difference Between Peginterferon Alfa 2A and 2B
     – Comparison of Key Differences 

Key Terms 

Chronic Hepatitis C Infection, Interferon, Peginterferon-Alfa-2A, Peginterferon-Alfa-2B, PEG Chain

What is Peginterferon Alfa 2A 

Peginterferon-alfa-2a (PEG-IFN alfa-2a) is a form of monopegylated interferon with a 40-kDa branched PEG moiety. It consists of 4 major positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon alfa-2a. Besides, the attachment of the PEG moiety occurs through stable amide bonds. Hence, peginterferon-alfa-2a exists as an intact molecule in the circulation. As such, it obtains a longer half-life.

Figure 1: Peginterferon-Alfa-2A

Moreover, it shows less clearance with respect to the native peginterferon-alfa-2a. Thereby, peginterferon-alfa-2a can be given once weekly, independent of the body weight. Additionally, it has a restricted volume distribution; in the blood and organs. 

What is Peginterferon Alfa 2B 

Peginterferon-alfa-2b (PEG-IFN alfa-2b) is the second form of monopegylated interferon with a 12 kDa linear PEG moiety, covalently attached to the His34 residue. Also, it has 14 major positional isomers. However, the attachment of the PEG chain occurs through an unstable urethane bond, which is subject to hydrolysis once injected, and thus, releasing native interferon-alpha-2b.

Figure 2: Peginterferon-Alfa-2B

On that account, peginterferon-alpha-2b has a shorter half-life in serum and requires bodyweight-based dosing. Besides, peginterferon-alfa-2b has a wider distribution in the body. 

Similarities Between Peginterferon Alfa 2A and 2B  

• Peginterferon-alfa-2a  and 2b are the two types of pegylated interferons widely available for the treatment of chronic hepatitis C (HCV) infection.  
• They are the modified forms of interferon, a  drug that mimics a protein in the body that the immune system uses to destroy viruses.    
• They contain a covalently attached polyethylene glycol (PEG) moiety, which results in differences in immunologic, pharmacokinetic, and in turn, their pharmacodynamic properties.  
• PEG is an inert molecule, which reduces the degradation of protein when cross-linked while retaining the biological activity of proteins.  
• Still,  PEGs compose of monomeric ethylene glycols linked together, forming complex chains. This, in turn, produces an enormous diversity in the chains of PEG by linking ethylene glycols in different lengths and different branching patterns.  
• Also,  they differ in sizes depending on the type of PEG chain attached to the interferon.  
• The general recommendation for the treatment of patients with chronic hepatitis C involves combination therapy with PEG-IFN (alfa-2a or  alfa-2b) and ribavirin (RBV).  Here, ribavirin or tribavirin is an antiviral drug used to treat RSV  infection, some hemorrhagic fevers, as well as hepatitis C. Usually,  it helps to maximize the response rates in infected patients.  
• For hepatitis B, they are administrated alone.  
• Basically,  they avoid large fluctuating serum concentrations and the inconvenient dosing regimens associated with conventional interferon alfa.  
• Also,  they significantly increase in sustained virological response rates in comparison to the standard interferons.  
• However,  they have similar effectiveness between alfa-2a and alfa-2b in the sustained virological response rate.   

Difference Between Peginterferon Alfa 2A and 2B 

Definition 

Peginterferon-alfa-2a refers to a form of the recombinant drug with a branched, 40 kDa PEG chain, which is covalently attached to the interferon via stable amide bonds to lysine residues. On the other hand, peginterferon-alfa-2b refers to the other form of the recombinant drug with a linear 12 kDa PEG chain, which, primarily, is attached covalently to histidine-34 of the interferon. 

Commercial Name 

The commercial name for peginterferon-alfa-2a is Pegasys, while the commercial name for peginterferon-alfa-2b is Pegatron. 

Size and the Structure of the PEG Chains 

Peginterferon-alfa-2a contains a branched, 40 kDa PEG chain, but peginterferon-alfa-2b contains a linear, 12 kDa PEG chain. 

Attachment Sites of PEG Chains 

Peginterferon-alfa-2a contains the PEG chain attached to either Lys31, Lys121, Lys131 or Lys134, and thus, forming positional isomers. But, peginterferon-alfa-2b contains the PEG chain attached to the His34.  

Circulation  

Peginterferon-alfa-2a circulates as an intact molecule, but peginterferon-alfa-2b has an unstable urethane bond, which undergoes hydrolysis once injected, and thus, releasing native interferon-alpha-2b.  

Half-Life 

Peginterferon-alfa-2a has a longer half-life than peginterferon-alfa-2b. 

Dosing 

Peginterferon-alfa-2a can be given once weekly, independently of the body weight. But, peginterferon-alfa-2b requires body weight-based dosing. 

Absorption and Distribution 

Peginterferon-alfa-2a has a relatively constant absorption and is mostly distributed in the blood and organs, but peginterferon-alfa-2b has both a rapid absorption and a wider distribution in the body. 

Conclusion 

Peginterferon-alfa-2a is one of the two forms of modified interferons important in the treatment of HCV. Generally, it contains a branched-chain, 40 kDa PEG chain, which is covalently attached to the lysine residues of the interferon. Thus, a significant feature of it is the stability, which aids in circulating the peginterferon-alfa-2a as an intact molecule. Therefore, it has a longer half-life. On that account, it can be given once a week, independently of the body weight. In contrast, peginterferon-alfa-2b is the other form of modified interferon used to treat HCV. But, it contains a linear chain of 12 kDa PEG chain, which is attached covalently to the His34. Also, it undergoes hydrolysis and hence, peginterferon-alfa-2b has a shorter half-life. Thereby, it requires a body weight-based dosing. Hence, the main difference between peginterferon-alfa-2a and 2b is the type, the attachment of the PEG chain, and its effect.  

References:

1. Foster, Graham R. “Pegylated Interferons for the Treatment of Chronic Hepatitis C: Pharmacological and Clinical Differences between Peginterferon-Alpha-2a and Peginterferon-Alpha-2b.” Drugs, U.S. National Library of Medicine, 2010, Available Here.

Image Courtesy:

1. “Peginterferon alfa-2a” By Fallaner – Pegylating IFNs at His-34 improves the in vitro anti- viral activity through the JAK/STAT pathway (Public Domain) via Commons Wikimedia   
2. “Peginterferon alfa-2b” By Fallaner – Pegylating IFNs at His-34 improves the in vitro anti- viral activity through the JAK/STAT pathway (Public Domain) via Commons Wikimedia